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Recent research on placental, embryo, and brain organoids suggests that the COVID-19 virus may potentially affect embryonic organs, including the brain. Given the established link between SARS-CoV-2 spike protein and neuroinflammation, we sought to investigate the effects of exposure to this protein during pregnancy. We divided pregnant rats into three groups: Group 1 received a 1 ml/kg saline solution, Group 2 received 150 μg/kg adjuvant aluminum hydroxide (AAH), and Group 3 received 40 μg/kg spike protein + 150 μg/kg AAH at 10 and 14 days of gestation. On postnatal day 21 (P21), we randomly separated 60 littermates (10 male-female) into control, AAH-exposed, and spike protein-exposed groups. At P50, we conducted behavioral analyses on these mature animals and performed MR spectroscopy. Subsequently, all animals were sacrificed, and their brains were subject to biochemical and histological analysis. Our findings indicate that male rats exposed to the spike protein displayed a higher rate of impaired performance on behavioral studies, including the three-chamber social test, passive avoidance learning analysis, open field test, rotarod test, and novelty-induced cultivation behavior, indicative of autistic symptoms. Exposure to the spike protein (male) induced gliosis and neuronal cell death in the CA1-CA3 regions of the hippocampus and cerebellum. The spike protein-exposed male rats exhibited significantly greater levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and lactate and lower levels of brain-derived neurotrophic factor (BDNF) than the control group. Our study suggests a potential association between prenatal exposure to COVID-19 spike protein and neurodevelopmental problems, such as ASD. These findings highlight the importance of further research into the potential effects of the COVID-19 virus on embryonic and fetal development and the potential long-term consequences for neurodevelopment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD., Methods: Twenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively., Results: In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function., Conclusion: In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction/aim: Epilepsy is widely investigated as a common neurological disease requiring pharmacologically effective agents. N-acetyl cysteine (NAC), has become a remarkable molecule with its role in both antioxidant and glutaminergic modulation. There are many points and processes waiting to be revealed regarding the role of NAC in epilepsy., Materials and Methods: Pentylenetetrazole (PTZ) was administered to induce seizures in a total number of 48 Sprague-Dawley rats. 35 mg/kg PTZ dose as a sub-convulsive dose was administered to 24 animals to monitor EEG changes, while 70 mg/kg PTZ dose which was a convulsive dose was administered to 24 animals to determine seizure-related behavioral changes with the Racine's scale. 30 min before the seizure-induced procedure, NAC was administered at doses of 300 and 600 mg/kg as pretreatment to investigate anti-seizure and anti-oxidative effects. The spike percentage, the stage of convulsion, and the onset time of the first myoclonic jerk were evaluated to determine the anti-seizure effect. Furthermore, its effect on oxidative stress was determined by measuring both malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity., Results: There was a dose-dependent reduction in the seizure stage and prolonged onset time of the first myoclonic jerk in rats with NAC pretreatment. EEG recordings resulted in a dose-dependent decrease in spike percentages. Moreover, the same dose-dependent changes were observed in oxidative stress biomarkers, both 300 mg/kg NAC and 600 mg/kg decreased MDA levels and ameliorated SOD activity., Conclusion: We can report that 300 mg/kg and 600 mg/kg doses of NAC are promising with their reducing effect on convulsions and have a beneficial effect by preventing oxidative stress. In addition, NAC has been also determined that this effect is dose-dependent. Detailed and comparative studies are needed on the convulsion-reducing effect of NAC in epilepsy., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

It is still an urgent need to find alternative and effective therapies to combat epileptic seizures. Tacrolimus as a potent immunosuppressant and calcineurin inhibitor is emerging as promising drug to suppress seizures. However, there are few reports applying tacrolimus to epilepsy and providing data for its antiseizure properties. In this study, we investigated the antiseizure effects of 5 and 10 mg/kg doses of tacrolimus treatment priorly to pentylenetetrazol (PTZ) induction of seizures in rats. As an experimental design, we establish two independent rat groups where we observe convulsive seizures following 70 mg/kg PTZ and sub-convulsive seizures detected by electroencephalography (EEG) following 35 mg/kg PTZ. Thereafter, we proceed with biochemical analyses of the brain including assessment of malondialdehyde level as an indicator of lipid peroxidation and detection of superoxide dismutase (SOD) enzyme activity and PGF2α. Tacrolimus pre-treatment dose-dependently resulted in lesser seizure severity according to Racine's scale, delayed start-up latency of the first myoclonic jerk and attenuated the spike percentages detected by EEG in seizure-induced rats. However, only the higher dose of tacrolimus was effective to restore lipid peroxidation. An increase in SOD activity was observed in the PTZ group, mediated by seizure activity per se, however, it was greater in the groups that received treatment with 5 and 10 mg/kg of Tacrolimus. PGF2α bursts following PTZ induction of seizures were reversed by tacrolimus pre-treatment in a dose-dependent manner as well. We report that the well-known immunosuppressant tacrolimus is a promising agent to suppress seizures. Comparative studies are necessary to determine the possible utilization of tacrolimus in clinical cases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male Wistar rats were used in the study, divided into 3 groups of ten subjects. One group served as a control, the subjects in the other two were given 250 mg/kg/day of PPA by intraperitoneal injection over the course of 5 days to induce autism. The experimental design was as follows: Group 1: Normal control (orally-fed control, n = 10); Group 2 (PPA + saline, n = 10): PPA and 1 ml/kg/day % 0.9 NaCl saline via oral gavage; Group 3 (PPA + Modafinil, n = 10) PPA and 30 mg/kg/day Modafinil (Modiodal tablets 100 mg, Cephalon) via oral gavage. All of the groups were investigated for behavioral, biochemical, and histological abnormality. Autism-like behaviors were reduced significantly in the rats treated with PPA. TNF-α, Nerve Growth Factor (NGF), IL-17, IL-2, and NF-KB levels as well as MDA levels and lactate were significantly higher in those treated with PPA compared to the control group. Using immunohistochemical methods, the number of neurons and GFAP immunoreactivity was significantly altered in PPA-treated rats compared to the control. Using Magnetic Resonance Spectroscopy (MRS), we found that lactate levels were significantly higher in the PPA-treated rats, while creatinine levels were significantly decreased. In the rats administered with Modafinil, behavior, neuroinflammation, and histopathological changes brought about by PPA were significantly reversed. Our results demonstrate the potential role of Modafinil in ameliorating PPA-induced neuroinflammation in rats., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Epilepsy is a disease which affects between 1 and 2% of the population, and a large proportion of these people do not react to currently available anticonvulsant medications, indicating the need for further research into novel pharmacological therapies. Numerous studies have demonstrated that oxidative stress and inflammation occur during epilepsy and may contribute to its development and progression, indicating higher levels of oxidative and inflammatory parameters in experimental models and clinical patients. This research aimed to assess the impact of diclofenac sodium, a nonsteroidal anti-inflammatory medicine, on seizure and levels of oxidative stress and inflammatory biomarkers in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). 60 rats were randomly allocated to one of two groups: electroencephalography (EEG) recordings or behavioral evaluation. Rats received diclofenac sodium at three various doses (25, 50, and 75 mg/kg) intraperitoneally (IP) or a placebo, followed by intraperitoneal (IP) pentylenetetrazole, a powerful seizure-inducing medication. To investigate if diclofenac sodium had antiseizure properties, seizure activity in rats was evaluated using EEG recordings, the Racine convulsion scale (RCS) behaviour score, the duration of the first myoclonic jerk (FMJ), and the levels of MDA, TNF-α, and SOD. The average percentage of EEG spike waves decreased from 76.8% (placebo) to 64.1% (25 mg/kg diclofenac), 55.9% (50 mg/kg diclofenac), and 37.8% (75 mg/kg diclofenac). FMJ had increased from a mean of 58.8 s (placebo), to 93.6 s (25 mg/kg diclofenac), 185.8 s (50 mg/kg diclofenac) and 231.7 s (75 mg/kg diclofenac). RCS scores decreased from a mean score of 5.6 (placebo), to 3.75 (25 mg/kg diclofenac), 2.8 (50 mg/kg diclofenac) and 1.75 (75 mg/kg diclofenac). MDA levels reduced from 14.2 ng/gr (placebo) to 9.6 ng/gr (25 mg/kg diclofenac), 8.4 ng/gr (50 mg/kg diclofenac) and 5.1 ng/gr (75 mg/kg diclofenac). Likely, TNF-α levels decreased from 67.9 ng/gr (placebo) to 48.1 ng/gr (25 mg/kg diclofenac), 33.5 ng/gr (50 mg/kg diclofenac) and 21.3 ng/gr (75 mg/kg diclofenac). SOD levels, however, enhanced from 0.048 U/mg (placebo) to 0.055 U/mg (25 mg/kg diclofenac), 0.14 U/mg (50 mg/kg diclofenac), and 0.18 U/mg (75 mg/kg diclofenac). Diclofenac sodium (25, 50, and 75 mg/kg i.p.) effectively lowered the spike percentages and RCS scores linked with PTZ-induced epilepsy in rats, as well as significantly decreased MDA, TNF-α, IL-1β, PGE2 and increased SOD levels. Probably as a result of its anti-oxidative and anti-inflammatory effects, diclofenac sodium dramatically lowered seizure activity at both doses compared to placebo control. Each of these results were significant, with p-values of < 0.01, < 0.05. Therefore, the therapeutic application diclofenac sodium as a potential anticonvulsant should be investigated further., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A neurodevelopmental disease, autism spectrum disorder (ASD) occurs in males three times more commonly than girls. Higher prenatal testosterone exposure may result in autistic-like behaviour in boys, according to earlier research. It is unclear how fetal testosterone affects the development of autism. In this study, we tested the hypothesis that prenatal testosterone exposure in an animal model may result in autistic behaviours by modifying serotonin, dopamine, IGF-1 and oxytocin levels., Materials and Methods: Group 1 (control, n = 6) and Group 2 (testosterone undecanoate, n = 6) of female rats were randomly assigned. For 2-3 days during the oestrus cycle, female rats were housed with a reproductive male (three females/one male). On the 10th day of gestation, rats in Group 1 received 1 ml/kg% 0.9 NaCl saline, whereas rats in Group 2 received 250 mg/kg testosterone undecanoate. Until weaning on postnatal day 21 (P21), the mothers were permitted to care for their pups. On P21, 40 littermates-10 male and female for control and 10 male and female from mothers that exposed to testosterone-were arbitrarily split up and housed. On P50, these mature rats were tested for their behaviour. The rats were then sacrificed. The brain tissue was subjected to histological examinations as well as biochemical tests for homovanillic acid (HVA), 5-Hydroxyindoleacetic acid (5-HIAA), oxytocin and insulin-like growth factor-1 (IGF-1)., Results: The groups differed significantly in the behavioural examinations (three-chamber social test, passive avoidance learning analysis, open field test), with the testosterone-exposed groups exhibiting autistic symptoms to a higher extent. When compared with the control groups, testosterone exposure caused significant histological changes in the hippocampus CA1 and CA3 areas, including gliosis and cell death of neurons. In the testosterone-exposed groups, HVA, 5-HIAA and IGF-1 tissue expressions in the brain elevated, whereas oxytocin levels reduced. These findings point to a potential connection between neurodevelopmental disorders like ASD and exposure to testosterone during gestation., Conclusion: Overall, we revealed that prenatal testosterone exposure led to autistic traits by elevating serotonin, dopamine and IGF-1 levels while lowering oxytocin levels., (© 2022 International Society for Developmental Neuroscience.)

Purpose The aim of this study is to investigate the benefits of atorvastatin on the propionic acid-induced autism model via increasing sphingosine-1-phosphate and anti-inflammatory actions with imaging and brain tissue investigations. Materials and methods Twenty-five mg/kg/day/rat of propionic acid (PPA) was administered intraperitoneally to 20 male Wistar rats, and 10 male Wistar rats were fed orally. Study groups were designed as follows: Group 1: Control Group (orally fed control, n=10); Group 2 (PPA+saline, n=10); Group 3 (PPA+Atorvastatin, n=10). The brain biochemical and histopathology assessments and magnetic resonance (MR) imaging were conducted across groups in order to compare them. Results The PPA+Atorvastatin group was found to have significantly lower levels of brain malondialdehyde, IL-2 level, IL-17, tumor necrosis factor-alpha (TNF-α), and lactate compared to the PPA+saline group. The PPA+Atorvastatin group had higher levels of nerve growth factor and nuclear factor erythroid 2-related factor 2 (NRF-2) and sphingosine-1-phosphate. In histopathology assessments, the PPA+Atorvastatin group was found to have significantly higher neuronal counts of CA1 and CA2 in the hippocampus, and Purkinje cells in the cerebellum. Conclusions Current findings suggest that atorvastatin increases sphingosine-1-phosphate levels and decreases inflammatory actions which characterize the autism rodent model implemented in this study. These preliminary results have to be confirmed by further experimental and clinical studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Durankuş et al.)

Epilepsy is a prevalent and frequently devastating neurological disorder defined by recurring spontaneous seizures caused by aberrant electrical activity in the brain. Over ten million people worldwide suffer from drug-resistant epilepsy. This severe condition requires novel treatment approaches. Both oxidative and nitrosative stress are thought to have a role in the etiology of epilepsy. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that is used to treat type-2 diabetes mellitus. According to recent studies, Liraglutide also shows neuroprotective properties, improving memory retention and total hippocampus pyramidal neuronal population in mice. The purpose of this investigation was to determine the anti-seizure and anti-oxidative effects of liraglutide in a pentylenetetrazole (PTZ)-induced rat model of epilepsy. 48 rats were randomly assigned to two groups: those who had electroencephalography (EEG) recordings and those who underwent behavioral assessment. Rats received either intraperitoneal (IP) liraglutide at two different dosages (3-6 mg/kg) or a placebo, followed by pentylenetetrazole (IP). To determine if liraglutide has anti-seizure characteristics, we examined seizure activity in rats using EEG, the Racine convulsion scale (RCS), the time of first myoclonic jerk (FMJ), and MDA, SOD, TNF-α, IL-1β and GAD-67 levels. The mean EEG spike wave percentage score was reduced from 75.8% (placebo) to 59.4% (lower-dose) and 41.5% (higher-dose). FMJ had increased from a mean of 70.6 s (placebo) to 181.2 s (lower-dose) and 205.2 s (higher-dose). RCS was reduced from a mean of 5.5 (placebo) to 2.7 (lower-dose) and 2.4 (higher-dose). Liraglutide (3 and 6 mg/kg i.p.) successfully decreased the spike percentages and RCS associated with PTZ induced epilepsy, as well as considerably decreased MDA, TNF-α, IL-1β and elevated SOD, GAD-67 levels in rat brain. Liraglutide significantly decreased seizure activity at both dosages when compared to control, most likely due to its anti-oxidant and anti-inflammatory properties. The potential clinical role of liraglutide as an anti-seizure medication should be further explored., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To demonstrate the curative effect of digoxin on peripheral nerve damage with its anti-inflammatory role on interleukin (IL)-17., Material and Methods: The study was conducted with 30 male Sprague Dawley albino mature rats, of which 10 formed the control group, 10 were surgically treated and administered saline (group S), and another 10 were surgically treated and administered digoxin (group D). Motor functions and immunohistochemical and biochemical variables of the rats were assessed after therapy., Results: The amplitude of the inclined plane test scores and the compound muscle action potential levels were greater in group D than in group S. Likewise, there were higher nerve growth factor percentages, higher axon counts, and lower fibrosis score percentages in group D than is group S. Lastly, lower tissue malondialdehyde and plasma IL-17 levels were determined in group D, while the IL-10 level was higher., Conclusion: Digoxin contributes to nerve healing and neuroprotective effect by demonstrating its anti-inflammatory effect on IL-17. It can be considered an adjunctive therapy for peripheral nerve injury.

Cisplatin is commonly used in the treatment of lung, genitourinary, and gastrointestinal cancers. Peripheral neuropathy is the most important side effect, leading to a decrease in the dose of cisplatin or its complete cessation in the early period. 16 rats were given cisplatin at a dose of 2.5 mg/ kg/day twice a week for 4 weeks to induce neuropathy model. The rats taking Cisplatin were divided into 2 groups. Group 1 rats (n = 8) were given 1 ml/kg/day 0.9 % NaCl intraperitoneally, and Group 2 rats were given 10 mg/kg/day Propofol intraperitoneally daily for 4 weeks. The remaining 8 rats served as the control group. At the end of the study, all animals were tested for motor functions. Blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF-α), glutathione (GSH), IL-6 and HSP-70 levels. Electromyography findings revealed that compound muscle action potential (CMAP) amplitude was significantly higher in the cisplatin-Propofol group than in the cisplatin-saline group. Also, cisplatin-Propofol treated group showed significantly lower TNF-α, MDA and IL-6 levels and higher GSH and HSP-70 levels than cispalatin-Saline group (p < 0.01, p < 0.001). In addition, while the CMAP latency was decreased in the propofol group, the CMAP amplitude was increased, and a significant improvement was observed in the Inclined test scores. Besides, histological examinations showed an increase in axon diameter and NGF expression with Propofol treatment. This study demonstrated that Propofol exerts protective activity against cisplatin-induced neurotoxicity by increasing endogenous antioxidants and reducing lipid peroxidation and inflammation (Tab. 3, Fig. 4, Ref. 30). Text in PDF www.elis.sk Keywords: cisplatin, neuropathy, propofol, oxidative damage, ınflammation.

Aim: Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined., Design and Methods: In total, 18 adult sprague-dawley rats were classified into 3 groups; control ( n  = 6), STZ + Saline ( n  = 6) and STZ + Dexpanthenol ( n  = 6). Twelve AD-induced rats through STZ-injection (3 mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000 mg/kg/day, i.p.) for 3 weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3)., Results: It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-α in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects., Conclusion: Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.

Objective: We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats., Methods: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed., Results: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05)., Conclusions: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

Alzheimer's disease (AD) is by far the most common cause of cognitive impairment in older adults. Current treatments are entirely focused on the symptoms of AD. A complex etiology for AD has been proposed recently, in which AD leads in elevated levels of inflammation. We previously studied digoxin's involvement in the sporadic-AD intracerebroventricular (ICV)-streptozotocin (STZ) animal model due to its anti-inflammatory and neuroprotective characteristics. 18 adult sprague-dawley rats were split into three groups: control (n = 6), STZ + Saline (n = 6), and STZ + Digoxin (n = 6). Twelve AD-induced rats were split into two groups using stereotaxy five days after STZ injection (3 mg/kg) into both lateral ventricles: one group got digoxin (0.1 mg/kg/day, i.p.) for three weeks, while the other group received saline. Following treatment, each subject was subjected to a passive avoidance learning (PAL) test, followed by brain tissue harvesting. The levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured in the brain, and neurons were counted using Cresyl violet staining in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3) cornu ammonis (CA3). ICV-STZ significantly shortened PAL latency, increased brain TNF-α levels, decreased brain ChAT activity, and decreased hippocampus neuron number. On the other hand, digoxin significantly reduced all of these STZ-induced deleterious effects. Digoxin significantly rescued rats from memory loss caused by ICV-STZ by decreasing hippocampal cell death, neuroinflammation, and cholinergic deficiency. These findings suggest that digoxin may be beneficial in treating cognitive impairment and Alzheimer's disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetic neuropathy (DN) is the most common degenerative complication associated with Diabetes Mellitus. Despite widespread awareness about DN, the only effective treatments are blood glucose control and pain management. The aim of the current study was to determine the effect of intramuscular adipose-derived mesenchymal stem cell (AMSC) transplantation on sciatic nerves in DN using EMG and histological analyses. A total of 27 mice were randomly divided into three groups: control group, DN group and AMSC group. In EMG, CMAP amplitude in the sciatic nerves was lower, but distal latency was higher in the DN group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AMSC group compared with the DN group. Distal latency in the sciatic nerve was lower in the AMSC group compared with the DN group. Histologic examination of the tissues in the animals treated with AMSC showed a remarkable improvement in microscopic morphology. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted AMSC was selectively localized in the sciatic nerves. Transplantation of AMSC increased protein expression of S100, cdk2, NGF and DHH, all of which, interfered with DN onset in sciatic nerves. The findings of the present study suggest that AMSC transplantation improved DN through a signal-regulatory effect on Schwann cells, neurotrophic actions and restoration of myelination.

Epilepsy is a widespread and mainly severe neurological condition portrayed by recurring spontaneous seizures caused by the brain's abnormal electrical activity. According to new research, inflammation may be both a result and the cause of epileptic seizures. The highest zinc levels in the brain have been found in the hippocampus which is one of the most studied regions of the brain regarding epilepsy. Zinc may have an anti-inflammatory potential as zinc co-factors affect numerous biochemical and physiological reactions. In this study, we evaluated the effects of intraperitoneal zinc administration on seizure activity in murine PTZ model. Rats received either intraperitoneal (IP) zinc sulfate at two different dosages (50-100 mg/kg) or a placebo followed by pentylenetetrazole (IP), a strong seizure-inducing drug. The spike percentages were considerably lower in the PTZ (35 mg/kg) and 50 or 100 mg/kg zinc-treated groups (A3 and A4) than in the PTZ (35 mg/kg) and saline-treated group (A2; p may be used as an adjuvant therapy in combination with other antiepileptic drugs in the future (Tab. 3, Fig. 1, Ref. 27) Keywords: anti-seizure effect of zinc, epilepsy, abnormal electrical activity, antiepileptic drugs, rat model.

Background: Sepsis is one of the leading causes of death in intensive care units worldwide. Vitamins C and E are natural antioxidants and anti-inflammatory agents. Suppressing the inflammation is an important treatment target because it plays a role in the pathophysiology of sepsis. The purpose of this study was to investigate the effect of vitamins C and E treatment in rats with sepsis-induced lung damage., Methods: In this animal study, fecal intraperitoneal injection procedure (FIP) was performed on 30 of 40 rats included for creating a sepsis model. Rats were randomly assigned into four groups: Group 1, control group (no procedure was applied, n = 10), Group 2, FIP (untreated septic group n = 10), Group 3, FIP+vitC (treated with 500 mg/kg/day ascorbic acid, n = 10), and Group 4, FIP+vitE (treated with 300 mg/kg/day alpha-tocopherol, n = 10). Chest CT was performed in all rats and density of the lungs was measured by using Hounsfield unit (HU). Histopathological examination of lung damage was performed, and blood samples were collected for biochemical analysis., Results: TNF-α, CRP, IL 1-β, IL-6, and MDA plasma levels in groups treated with vitamin C or vitamin E were lower than in the FIP group. Histological scores in groups treated either with vitamin C or vitamin E were significantly lower as compared to those in the FIP group. The HU value of lung in groups treated wither with vitamin C or vitamin E were lower than that in the FIP group (p < 0.05)., Conclusion: The rats treated either with vitamin C or E showed improved results for sepsis. We think that they can be used as adjuvant therapy for septic patients because of their effectivity and low costs (Tab. 3, Fig. 2, Ref. 27).

Purpose: Life expectancy of cancer patients determine the regimen of treatment. There is no feasible marker that determines the survival other than the stage of the disease or other patients related factors. Bilirubin can be a revealing marker for these. The effect of bilirubin may be due to the fact that the genetic and biochemical processes of bilirubin also modulate the tumour microenvironment. Radiotherapy and bilirubin can produce an effect similar to metformin via AMPK pathway., Materials and Methods: This analysis was performed retrospectively in a cohort of 80 patients with a diagnosis of locoregional lung cancer with bilirubin levels in the accepted range. Receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cut-off points. Pre-treatment serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) levels and tumour volumes in the prognosis of the patients were investigated., Results: The cut-off points for serum TBIL, DBIL and IBIL were 0.565 mg/dL, 0.105 mg/dL and 0.415 mg/dL,respectively. High TBIL 47.5 %, high DBIL and high IBIL were observed in 45 % of the entire patient population. The overall survival was three times longer in the high TBIL group than in the low TBIL group (OS; Hazard Ratio (HR), 0.33; 95% CI 0.16-0.70; p <0.001), locoregional free survival (LRFS; HR, 0.44; 95% CI 0.27-0.71; p <0.001) and distant metastasis-free survival (DMFS; HR, 0.44; 95% 0.25-0.80; p < 0.001). Similarly, high DBIL and high IBIL levels have been associated with longer OS, LRFS, and DMFS with significant differences. In addition, in the survival analysis of the cohort stratified with gross tumour volume (GTV) 128.5cc and TBIL 0.565 cut-off values; In the comparison of high TBIL and low TBIL groups, a significantly longer OS was observed in the high TBIL group in the patients with a GTV volume greater than128.5cc (p <0.001)., Conclusion: Plasma bilirubin level at the time of diagnosis affects the survival of the patients independent of cancer stage and tumour volume. Possible additive interactions of radiotherapy and bilirubin are discussed with their pathophysiological mechanisms (Tab. 2, Fig. 7, Ref. 26).

Aim: To study (1) ovarian and endometrial damage caused by the hyperglycemia and (2) the effects of dichloroacetic acid (DCA) on follicular reserve and endometrial damage in streptozocin induced diabetic rats., Methods: This study consisted 24 rats randomly separated into three groups. A diabetes model was achieved in 16 rats experimentally, and normoglycemic eight rats were assigned as control group (Group 1). The rats with diabetes were randomly separated to two groups: 1 mL/kg/day intraperitoneal 0.9% NaCl was given to eight rats as diabetic vehicle (Group 2) and 10 mg/kg/day DCA was given to other eight rats as DCA treated group (Group 3). Hysterectomy with bilateral oophorectomy was performed for histopathological evaluation and blood samples were collected after 4 weeks., Results: Diabetes caused ovarian and endometrial damage (p < 0.0001). Pentraxin-3 (PTX-3), lactic acid, and transforming growth factor-beta (TGF-β) were higher (p < 0.05, p < 0.05, and p < 0.0001, respectively), whereas anti-Mullerian hormone (AMH) was lower in diabetic rats (p < 0.05). These findings reflected the diabetic damage in the genital tract and diminished ovarian reserve occurred via fibrosis, severe inflammation, and oxidative stress. DCA improved the histopathological fibrosis and degeneration in the ovaries and endometrium (p < 0.05). There was a concominant decrease of TGF-β and lactic acid levels with DCA treatment (p < 0.05). DCA also improved ovarian reserve with higher AMH levels (p < 0.05)., Conclusions: The several unfavored changes in the endometrium and ovaries due to diabetes have been determined in this present study. DCA might provide the continuity of the endometrial cycle, physiological endometrial structure, ovarian follicular growth, oocyte maturation, and physiological ovarian function by decreasing the lactate levels via inhibiting pyruvate dehydrogenase kinase enzyme., (© 2021 Japan Society of Obstetrics and Gynecology.)

Objective: Peripheral nerve injuries occur mostly as a result of mechanical trauma. Due to the microvascular deterioration in peripheral nerve damage, it becomes challenging to remove free oxygen radicals. Gallic acid is a powerful antioxidant with anti-inflammatory effects and a free radical scavenger. The purpose of the study is to show that gallic acid contributes to the restorative effect in mechanical nerve damage, considering its antioxidant and anti-inflammatory effects., Methods: Thirty male Sprague Dawley albino mature rats were included in the study. Ten of them constituted the control group, 10 out of 20 rats for which sciatic nerve damage was caused, constituted the saline group, and 10 formed the gallic acid group. Post-treatment motor functions, histological, immunohistochemical, and biochemical parameters of the rats were evaluated., Results: Compared to the surgery+saline group, lower compound muscle action potential (CMAP) latency, higher CMAP amplitude, and higher inclined plane test values were found in the surgery+gallic acid group. Similarly, a higher nerve growth factor (NGF) percentage, a higher number of axons, and a lower percentage of fibrosis scores were observed in the surgery+gallic acid group. Finally, lower tissue malondialdehyde (MDA) and higher heat shock protein-70 (HSP-70) values were determined in the surgery+gallic acid group., Conclusion: Gallic acid positively affects peripheral nerve injury healing due to its anti-inflammatory and antioxidant effects. It has been thought that gallic acid can be used as a supportive treatment in peripheral nerve damage.

Objectives: to investigate the effects of hyperosmolar state (HS) on immune response and inflammation via the NFAT5 pathway and examine whether immune-mediated conditions trigger autism-like behavior in offspring., Methods: a pregnant rat model was performed by administering hyperosmotic solutions. Pregnant rats were divided into 2 main groups; control (group I) and hyperosmolar groups (group II). Control group rats were given % 0.25 NaCI (tap water) (n = 6), the Hyperosmolar (HO) group was further subdivided into 3 groups as; Group II a rats which were given % 3 hypertonic NaCl (n = 6), Group II b rats were given mineral water (% 3 NaHCO3+magnesium+calcium content) (n = 6), and Group II c rats were given Ayran (% 0.8 NaCl content) (n = 6). Their offspring were examined for behaviors, biochemical and histological abnormality., Results: in offspring, TNF- α, IL-17, NFAT-5, and NGF levels in the brain were significantly higher in hyperosmotic solution groups than in control rats. Exposure of pregnant rats to hyperosmotic solution resulted in autism-like behaviors in their offspring. Through immunohistochemical methods, we found that CA1 and CA2 of the hippocampus indicated decreased number of neurons in hyperosmotic solution groups compared with the control group., Conclusions: our findings once again emphasized that the immune-mediated conditions involved in the pathophysiology of autism. NFAT5 pathway may be a key factor in the development of neuroinflammation by hyperosmotic solutions., (Copyright © 2021. Published by Elsevier Inc.)

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25 mg/kg and 50 mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2 s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5 nmol/gr to 51.09 nmol/gr (lower-dose), 33.2 nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.

Purpose: Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication of ovarian stimulation in reproductive medicine. Here, we aimed to investigate the role of oxytocin (OT) and cabergoline in the prevention and alleviation of the OHSS in an animal model., Methods: Thirty-five female immature Wistar rats were randomly assigned to five groups. The control group (n = 7) received saline only for five consecutive days. Remaining twenty-eight rats received 10 IU of pregnant mare serum gonadotropin (PMSG) followed by 30 IU of human chorionic gonadotropin (hCG) to induce OHSS. Group 2 (n = 7) was managed with no additional intervention after the induction of OHSS. Group 3 (n = 7) received 100 μg/kg cabergoline 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Group 4 (n = 7) and group 5 (n = 7) received 80 μg/kg and 160 μg/kg OT after induction of OHSS, respectively. Oxytocin was administered 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Body and ovary weight, vascular permeability (VP), VEGF expression in the ovaries, and levels of VEGF in the peritoneal fluids were examined in all animals., Results: Cabergoline and OT reduced body weight, ovary weight, and VP compared to that of the OHSS group (p < 0.05). VEGF expressions in ovaries and peritoneal VEGF levels were decreased in cabergoline and OT groups compared to that of the OHSS groups (p < 0.001 for cabergoline and OT-80 μg/kg; p < 0.00001 for OT-160 μg/kg). However, there was no statistically significant difference in these parameters between the OT and cabergoline groups., Conclusion: Both OT and cabergoline were active in the alleviation of OHSS through suppression of VEGF and VP. Overall, we conclude that OT is effective for downregulation for VEGF and improvement in vascular permeability in OHSS.

Background Insulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation. Methods Thirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose <40 mg/dl was defined as hypoglycemia. Electrocardiograms (ECG) were taken in lead I (DI), and QTc was calculated by using Bazett's formula. Results Group 2 (insulin + saline) showed that it had a significantly prolonged QTc interval as compared to the control group (p<0.0001). However, treatments of the rats with metoprolol, pilocarpine, and diltiazem significantly prevented prolongation of the QTc interval as compared to the insulin + saline group (p<0.005, p<0.005, and p<0.01, respectively). Conclusion The findings of the present study demonstrated the efficacy of metoprolol, pilocarpine, and diltiazem in the prevention of hypoglycemia-induced QTc prolongation in male rats., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Cagiltay et al.)

The aim of the present study was to investigate the effect of dexpanthenol on nerve healing following neurorrhaphy in lacerated peripheral nerves. A total of 30 mature Sprague Dawley rats were used. Surgical sciatic nerve dissection and repair was performed on an experimental group of 20 rats. The remaining 10 rats were designated as the control group. The experimental group was divided into 2 subgroups. The surgery + saline group (SSLE; n=10) was given 1 ml/kg 0.9% sodium chloride saline intraperitoneally. The surgery + dexpanthenol group (SDPL; n=10) rats were given 500 mg/kg/day dexpanthenol intraperitoneally. Histological evaluation of the sciatic nerve tissue revealed that the fibrosis score was significantly lower in the SDPL group than in the SSLE group (P<0.001). Electrophysiological evaluation of compound muscle action potential (CMAP) indicated that the CMAP level in the SDPL group was significantly higher than that of the SSLE group (P<0.001), and the CMAP latency period was lower in the SDPL group compared with the SSLE group (P<0.001). In addition, the SDPL group malondialdehyde level was significantly lower than that of the SSLE group (P<0.001). Functional evaluation with an inclined plane test revealed a significant difference between the SSLE (39.6±5.5 ˚ ) and SDPL (79.1±6.93 ˚ ) groups (P<0.001). Dexpanthenol was observed to have a positive effect on nerve tissue repaired with neurorrhaphy in a rat sciatic model of laceration-type injuries similar to those frequently encountered in the clinic., (Copyright: © Karahan et al.)

Background: Colistin utilization has gradually increased worldwide with the rising of multidrug-resistant (MDR) gram-negative bacilli despite its nephrotoxicity. Lipid emulsion (LE) is widely used for the toxic overdose treatment of various drugs., Objective: The aim of the present study is to evaluate the effect of lipid emulsion on the improvement of renal damage in colistin-induced nephrotoxicity with an experimental Sprague Dawley rat model., Methods: Twenty-four male Sprague Dawley rats were initially assigned to 2 random groups. Sixteen rats were given a single dose of 20 mg/kg colistin, and eight rats received no medication (control group). Sixteen rats that were administered colistin were sub-divided into 2 groups. Group 1/LE rats (n = 8) were given 20 ml/kg solution of lipid emulsion, and group 2/S rats (n = 8) were given 20 ml/kg/day (i.p.) of 0.9% NaCl saline; both were administered for 10 days. Then tubular injury was evaluated histopathologically. Serum levels of blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), and creatinine were measured. Besides, malondialdehyde (MDA) levels were determined in tissue samples for the assessment of lipid peroxidation., Results: The mean percent of tubular epithelial cell injury and tubular dilatation was found significantly higher in group 2/S than in control and group 1/LE (p < 0.0001 and < 0.001; respectively). KIM-1 and MDA levels were also statistically higher in group 2/S than in control and group 1/LE. (p < 0.0001 and < 0.0001; respectively). Additionally, serum BUN and creatinine levels of group 2/S were significantly greater than control and group 1/LE (p < 0.0001 and < 0.0001; respectively)., Conclusion: In this present study, we determined that colistin-induced proximal tubular damage was decreased histopathologically and serologically by the effect of lipid emulsion. Thus, our findings may guide future studies on the clinical use of colistin, particularly in MDR positive intensive care infections., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Sepsis is a systemic infection reaction and intravascular volume therapy plays a crucial role in it's treatment. Acute respiratory distress syndrome (ARDS) occurs in the lungs, the most affected organ. This study aimed to investigate the different effects of fluid therapy on ARDS caused by sepsis., Method: To form a sepsis model, cecal ligation and puncture (CLP) procedure were performed on 44 adult rats. Divided into six groups; normal, CLP group, those treated with 40 ml/kg 0.9 % NaCl, 3 % NaCl (hypertonic saline), Ringer Lactate and Hydroxyethyl starch. After 24 hours treatments, histopathological examination of the lungs were done, and the plasma levels of CRP, TNF-α and IL-6 and paO2 were measured., Results: The scores of all histological parameters of the group treated with hypertonic saline were significantly lower than of the other groups (p < 0.001). Likewise, according to the arterial blood gas results, paO2 was significantly higher (p < 0.01) in the hypertonic saline group compared to the other groups, and paCO2 was significantly lower (p < 0.01). CRP, TNF-α and IL-6 levels of inflammatory markers were also significantly lower in hypertonic saline groups compared to other groups (p < 0.001)., Conclusions: Our study shows that treatment with hypertonic saline reduces the progression of ARDS in sepsis (Tab. 3, Fig. 4, Ref. 49).

Although the exact pathophysiology of critical illness polyneuropathy (CIP) is still unknown, there are several hypotheses, some of which are increased inflammation and oxidative stress. We used rodent sepsis model in which we induced sepsis through cecal ligation followed by cecal puncture. We then administered ascorbic acid (AA) and evaluated outcomes. The levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukins (IL)-6 in the plasma, and heat shock protein-70 (HSP-70) levels in the sciatic nerve were measured, and also electromyography analyses were performed. While plasma MDA, TNF-α, and IL-6 levels were decreased significantly with AA treatment, sciatic nerve levels of HSP-70 were significantly elevated in the AA group. A significant increase in compound muscle action potential (CMAP) amplitude and a significant decrease in CMAP latency were detected in the AA group. We observed healing effects of AA on a rat model of CIP and these effects seem to be related to its anti-inflammatory and antioxidant properties., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

This study aimed to investigate the protective and antioxidant role of losartan in ovarian ischaemia and ischaemia/reperfusion injury in an experimental ovarian torsion model. Thirty adult female rats were used. Rats were separated randomly into five groups; Group 1: sham group (abdominal wall was only opened and closed), Group 2: torsion group with 3-hour ischaemia using atraumatic vascular clips. Group 3: torsion + losartan group with 3-hour ischaemia 30 minutes after the administration of 40 mg/kg of losartan via oral gavage. Group 4: torsion-detorsion group with 3-hour ischaemia and 3-hour reperfusion (vascular clips were removed). Group 5: torsion-detorsion + losartan group with 3-hour ischaemia followed by administration of 40 mg/kg of losartan 30 minutes prior to a 3-hour detorsion/reperfusion. Ovarian tissue damage was scored by histopathological analysis. Ovarian tissue malondialdehyde (MDA) and plasma pentraxin 3 (PTX 3) levels were measured biochemically. In comparison with the sham group, both the torsion and torsion-detorsion groups had significantly higher scores for follicular degeneration, vascular congestion, oedema, haemorrhage, and leukocyte infiltration ( p <  .05). The aforementioned parameters significantly decreased in the torsion-detorsion + losartan group ( p <  .01) compared to those in the torsion-detorsion group. MDA and plasma PTX 3 levels were notably higher both in the torsion and torsion-detorsion groups compared with those in the sham group ( p <  .01). The current experimental ovarian torsion study suggests a protective role for losartan upon ischaemia and ischaemia/reperfusion injury in rat ovaries. Losartan may be a novel agent for decreasing ovarian ischaemia/reperfusion injury in ovaries.Impact statement What is already known on this subject? Among gynaecological emergencies, the diagnosis of ovarian torsion is highly difficult. A delayed diagnosis may lead to ovarian necrosis and subsequent loss of ovaries if timely surgical intervention is not performed, which is essential for the fertility and protection of ovarian functions in young patients. However, reperfusion of the ischaemic tissue might leads to more serious damage to the tissue than the damage caused by ischaemia. What the results of this study add? This study found that losartan, an Ang II type 1 receptor blocker which has been currently used for regulation of blood pressure, could be used experimentally to alleviate I/R injury in ovary through improving histological parameters, reducing tissue MDA and plasma PTX3 levels. To date, there is no study regarding the usage of losartan for alleviating I/R on ovary due to torsion. What the implications are of these findings for clinical practice and/or further research? Losartan may be suggested to have therapeutic value in patients with ovarian torsion. Further large clinical studies are necessary to prove the beneficial effect of losartan to prevent I/R injury on human ovaries.

Study Objectives: Methylene blue (MB) is an antioxidant that ameliorates ischemia-reperfusion injury in several tissues. We analyzed the effects of MB as an inhibitor of torsion-detorsion injury in rat ovaries., Methods: Rats were randomly divided into 5 groups. Group 1 was the sham group, in which only laparotomy was performed. Group 2 was the torsion group, with 3 hours of ischemia. Group 3 was the torsion + MB group, with 3 hours of ischemia after MB administration. Group 4 was the torsion-detorsion group, with 3 hours of ischemia and reperfusion. Finally, group 5 was the torsion-detorsion + MB group, with 3 hours of ischemia and MB administration before detorsion/reperfusion. Ovary injuries were histopathologically scored. Malondialdehyde (MDA) and total protein levels in ovarian tissues were determined, and long pentraxin-3 (PTX3) levels were measured in ovarian tissue using an enzyme-linked immunosorbent assay., Results: In comparing group 4 with group 5 and group 2 with 3, histopathological parameters reflecting injury were significantly increased in groups 4 and 2. Group 3 generated increased MDA levels when compared with group 2 (P < .05). However, there was no significant difference between groups 2 and 3 in terms of plasma PTX3 levels. MDA and PTX3 levels decreased in group 5 in comparison with group 4 for MDA (P < .000) and PTX3 levels (P < .01)., Conclusions: MB alleviated ischemia-reperfusion ovary injury in our experimental model., (Copyright © 2020 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis.

Purpose: Although cancer predominantly affects people at older ages, a substantial number of patients, like breast cancer patients, are diagnosed before they have completed their families or even before giving birth. Furthermore, cytotoxic chemotherapy may be required in addition to treat cancer survivors. The present study was conducted to investigate the protective effect of oxytocin (OT) on methotrexate (MTX)-induced ovarian toxicity in rats., Methods: Eighteen adult female Sprague-Dawley rats were used in the study. All rats were divided randomly into three groups. The control group (n = 6) received no treatment. The remaining 12 rats received a single dose of 20 mg/kg of MTX. Half of the rats (n = 6) were treated with 1 mg/kg/day of saline, and the other half (n = 6) were treated with 160 µg/kg/day of OT for 21 days. Then, blood samples were collected for biochemical analysis, and an ovariectomy was performed for histopathological examination., Results: Plasma malondialdehyde (MDA) and transforming growth factor-β (TGF-β) levels were significantly lower in the MTX + OT group compared to the MTX + saline group (p = 0.000036 for MDA; p = 0.0044 for TGF-β). AMH levels were also significantly higher in the MTX + OT group than in the MTX + saline group (p = 0.000036). The ovarian fibrosis percent was also notably lower in the MTX + OT group than in the MTX + saline group (p = 0.000036)., Conclusion: On the basis of these findings, OT is a promising agent for ameliorating harmful effects of MTX on rat ovaries in an experimental model.

Purpose: To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats., Methods: Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-α, Pentraxin-3 and malondialdehyde (MDA) levels., Results: AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-α, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05)., Conclusion: Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.

Introduction: Agomelatine is a potent MT1 and MT2 melatonin receptor agonist and a 5-HT2C serotonin receptor antagonist. The purpose of this study was to show the convulsion-reducing effect of agomelatine, in both clinical and electrophysiological terms, in a pentylenetetrazole (PTZ)-induced experimental epilepsy model in rats., Methods: The anticonvulsant activity of agomelatine (25 and 50 mg/kg) was evaluated in rat models of PTZ (35 and 70 mg/kg) and compared with the control groups., Results: Agomelatine administration at doses of 25 and 50 mg/kg resulted in a statistically significant decrease in convulsion scores and time to onset of myoclonic jerks compared to the control groups. In addition, comparison of the two doses employed showed that high-dose agomelatine (50 mg/kg) was significantly more effective than the lower dose. In addition to previous studies, we investigated the anticonvulsant effect of agomelatine using electroencephalogram (EEG). Administration of agomelatine at doses of 25 and 50 mg/kg in PTZ-induced seizures caused a significant decrease in the percentage of peak at EEG., Discussion: Our results suggest that agomelatine has anticonvulsant activity shown in PTZ-induced seizure model. The results also give some evidences that agomelatine can use on epileptic seizures, but more studies are needed., (© 2019. Akadémiai Kiadó Zrt.)

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein commonly used in the field of medicine to treat neutropenia. Granulocyte colony-stimulating factor has also crucial roles in ameliorating the ischemia/reperfusion (I/R) injury in particular tissues. In this study, we aimed to investigate the protective effect of G-CSF on ovarian damage in experimental ovarian I/R injury. Thirty adult female rats were used. Rats were separated randomly into 5 groups; Group 1: sham group (abdominal wall was opened and closed surgically), Group 2: torsion group with 3-hour ischemia using vascular clips. Group 3: torsion + G-CSF group with 3-hour ischemia 30 minutes after the administration intraperitoneal (i.p.) of 100 µg/kg of G-CSF. Group 4: torsion-detorsion group with 3 hour ischemia and 3 hour reperfusion. Group 5: torsion-detorsion + G-CSF group with 3 hour ischemia followed by 100 µg/kg of G-CSF i.p. administration 30 minutes prior to 3 hour of detorsion/reperfusion. Ovarian tissue damage was scored on histopathology. Ovarian tissue malondialdehyde (MDA) was measured biochemically. In comparison with the sham group, both the torsion and torsion-detorsion groups had significantly higher scores for follicular degeneration, vascular congestion, edema, hemorrhage, and leukocyte infiltration ( P < .05). When compared group torsion-detorsion + G-CSF to group torsion-detorsion, parameters aforementioned significantly decreased in group torsion-detorsion + G-CSF ( P < .05). Granulocyte colony-stimulating factor has also decreased MDA levels notably both in the torsion + G-CSF and torsion-detorsion + G-CSF groups ( P < .05, P < .01). Our experimental study suggests that G-CSF can be a novel agent for the treatment of ovarian I/R injury.

Background: Millions of individuals worldwide suffer from epilepsy, and up to 25% of patients have seizures that are resistant to currently available antiepileptic drugs. Hence, there continues to be a need for more seizure medications that are effective yet tolerable. Levodropropizine (LVDP) is an established antitussive drug that, based on preclinical data, may also have antiepileptic activity., Methods: We treated rats with either intraperitoneal (IP) LVDP at two different doses or placebo in randomized fashion and then exposed them to IP pentylenetetrazol (PTZ), a potent seizure-inducing compound. We measured the rats' subsequent seizure activity with electroencephalography (EEG), Racine's convulsion scale (RCS) and time to first myoclonic jerk (TFMJ) to determine whether LVDP has antiepileptic properties in our murine model for epilepsy., Results: When compared to placebo, LVDP at both doses significantly suppressed seizure activity. Mean EEG spike wave percentage score decreased from 76.8% (placebo) to 13.1% (lower dose) and 7.6% (higher dose, bothp <  0.0001). RCS decreased from a mean of 5.8 (placebo) to 1.83 (lower dose) and 1.16 (higher dose, both p <  0.05). TFMJ had increased from a mean of 65.1 s (placebo), to 247.3 s (lower dose) and 295.5 s (higher dose, both p <  0.0001)., Conclusions: Levodropropizine, a common antitussive drug, suppresses seizure activity in rats with PTZ-induced status epilepticus. Given the ongoing need to find effective therapies for refractory epilepsy, the possibility of using levodropropizine as an antiepilepticshould be further explored., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to evaluate the efficacy of trimetazidine(TMZ) after end-to-end repair in a peripheral nerve injury model., Method: We performed end-to-end primary repair of sciatic nerves in rats and showed TMZ's regenerative effect. For this objective 30 male Sprague Dawley albino rats were used. Surgery+water group, rats were assigned to a placebo group and were given water by oral gavage. Surgery+TMZ group, rats were given trimetazidine by oral gavage. All medications were given for 12 weeks. Motor function test was performed. Afterwards, electromyography (EMG) recording was done. Finally, blood samples were taken, the animals were euthanized andsciatic nerve was removed., Results: The amplitudes of compound muscle action potential (CMAP) increased significantly in the Surgery+TMZ group when compared with the group that have been given Surgery+Water. Nerve growth factor (NGF) immunoexpression in the Schwann cell was significantly increased in the Surgery+TMZ group compared with the Surgery+Water group. Moreover, fibrosis score was reduced in the Surgery+TMZ group compared to the Surgery+Water group.CONCLUSİONS: In conclusion, we demonstrated the superiority of TMZ on nerve healing in our experimental study which was evaluated with comparative groups (Tab. 3, Fig. 2, Ref. 31).

Background: Sick building syndrome (SBS) is defined as a condition occurring in those who live or work in a modern building and who suffer from symptoms such as headache, fatigue, lack of concentration and irritation of the skin and mucous membranes., Objectives: The aim of this study was to evaluate the relationship between personal characteristics, environmental factors and the prevalence of SBS among the secretaries working in a hospital., Method: In this cross-sectional study, questionnaires were administered to all secretaries who were working in Kutahya hospital in January and March 2018. The questionnaire used in the study included the sociodemographic characteristics of the participants and the question form "MM 040 NA Hospital" to evaluate SBS symptoms. These symptoms were the clinical symptoms reported by the secretaries as a result of exposure to factors within the hospital. Temperature, humidity, carbon dioxide concentration, light intensity and noise level were measured in the indoor environment of the hospital. Chi square test, Spearman's correlation coefficient and logistic regression models were used in the analysis of data., Results: The study was completed with 177 people, 61.6% women, and the mean age was 30.14±5.7. The prevalence of SBS was found to be 20.9%. The risk of SBS was found to be 2.9 times higher for females, 2.8 times higher for individuals who described the working environment as dusty, 2.6 times higher for subjects complaining of stuffy "bad" air, dry air and an unpleasant odour. All measurements were found to be within acceptable limits. The risk of SBS was found to be 1.2 times higher with increases in the measured noise level, and 2.1 times higher with increased carbon dioxide (CO2) concentrations., Conclusion: The factors impacting the risk of experiencing SBS were determined. Bearing these factors in mind, we think that hospital administrations should be informed about arrangements and measures that will improve the quality of the internal environment of the hospital.

Background: Previous studies have indicated an association between maternal metabolic conditions and general developmental disturbances of the offspring., Objective: We aimed to investigate the influence of long-term maternal fructose intake during gestation and lactation on neurobehavioral development of rat offspring., Methods: Twelve female Sprague Dawley rats were received either 30% fructose enriched water (n = 6) or regular tap water (control, n = 6) for 12 weeks. Then, control and fructose-received females were caged with a fertile male, and received 30% fructose and regular chow throughout pregnancy, delivery and until offspring's weaning. On P21, forty littermates (10 male control, 10 female control, 10 male fructose and 10 female fructose) were separated and housed with ad libitum access to standard food and tap water. Following behavioral evaluations at P50, brain levels of TNF-α, neuregulin 1 (NRG1), glutamic acid decarboxylase 67 (GAD67), nerve growth factor (NGF), insulin-like growth factor 1 (IGF-1), and 5-hydroxyindoleacetic acid (5-HIAA) were measured. Histologically, hippocampal neuronal density and GFAP expression were assessed., Results: Analysis of the behavioral tests (three-chamber social test, open field test, passive avoidance learning test and stereotypy test) revealed significant differences among the groups. Histologically, hippocampal CA1 and CA3 regions displayed significant alterations such as gliosis and neuronal cell death in fructose-exposed groups compare to controls. Biochemical measurements of the brain levels of TNF-α and neurodevelopmental markers showed significant differences between controls and fructose-exposed groups., Conclusion: These results suggest a possible link between the chronic maternal metabolic stress, such as long-term fructose intake, and neurodevelopmental disturbances in the offspring., (Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.)

Background: Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures., Methods: Laboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ)., Results: Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant., Conclusions: Dapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.

Purpose: The aim of this study is to investigate effects of exenatide (Glucagon-Like Peptide Agonist) replacement on bone mineral density (BMD) and microarchitecture in a surgical menopause-induced osteoporosis model in rats., Methods: In this study, 24 female Sprague-Dawley albino mature rats were used. Rats were assigned either to the group ovariectomized administered exenatide or to the control group. Bone Mineral Density (BMD), plasma cytokine levels and histomorphometric analysis were measured., Results: Ovariectomized rats showed significant decrease BMD values, trabecular counts, trabecular thickness and trabecular area. Also, significant increase trabecular separation and plasma TNF-α (Tumor Necrosis Factor) and IL-6 (Interleukin) levels. Exenatide treatment reversed these changes and it showed a considerable protective effect on trabecular bone microarchitecture., Conclusions: Exenatide may be a candidate for use in the treatment of postmenopausal osteoporosis and anti-inflammatory properties can be attributed this effects.

Background: Ovarian torsion is one of the most common gynecological emergencies, which especially affects women of reproductive age., Objectives: We aimed to evaluate the effect of Ginkgo biloba (GB) supplementation in ovarian ischemia/ reperfusion injury in an experimental torsion/de-torsion rat model., Material and Methods: This study was carried out in the Ege University Faculty of Medicine in Izmir, Turkey. Thirty mature female Sprague-Dawley albino rats were randomly divided into 5 groups: in Group 1 (control), the abdominal wall was only opened and closed; in the torsion group (Group 2), ischemia was induced for 3 h, using atraumatic vascular clips to create a torsion model; in the torsion/GB group (Group 3), the rats were given 80 mg/kg (oral gavage) of GB 30 min before torsion was induced and the torsion model was formed; in the torsion/de-torsion group (Group 4), the rats underwent 3 h of ischemia and then the vascular clips were removed and reperfusion took place for 3 h; in the torsion/de-torsion/GB group (Group 5), the rats underwent 3 h of ischemia followed by GB (oral gavage) 30 min prior to a 3-h reperfusion period. Ovarian tissue damage was evaluated by a histopathological scoring system. Ovarian tissue malondialdehyde (MDA) and plasma pentraxin-3 were measured., Results: In comparison with the sham group, both the torsion and torsion/de-torsion groups had significantly higher scores for follicular degeneration, vascular congestion, edema, hemorrhage, and leukocyte infiltration. Ginkgo biloba significantly decreased these scores in both groups. Ovarian malondialdehyde and plasma pentraxin 3 were significantly higher both in the torsion and torsion/de-torsion groups compared with the sham group. Ginkgo biloba decreased these levels significantly both in the torsion/GB and torsion/de-torsion/GB groups., Conclusions: Supplementing GB during a surgical procedure decreases ischemia/reperfusion injury to an ovary in an experimental rat model based on histopathological parameters, tissue malondialdehyde, and plasma pentraxin-3 levels.

Damage to peripheral nerves results in partial or complete dysfunction. After peripheral nerve injuries, a full functional recovery usually cannot be achieved despite the standard surgical repairs. Neurotrophic factors and growth factors stimulate axonal growth and support the viability of nerve cells. The objective of this study is to investigate the neurotrophic effect of exenatide (glucagon like peptide-1 analog) in a rat sciatic nerve neurotmesis model. We injected 10 μg/d exenatide for 12 weeks in the experimental group ( n = 12) and 0.1 mL/d saline for 12 weeks in the control group ( n = 12). We evaluated nerve regeneration by conducting electrophysiological and motor functional tests. Histological changes were evaluated at weeks 1, 3, 6, and 9. Nerve regeneration was monitored using stereomicroscopy. The electrophysiological and motor functions in rats treated with exenatide were improved at 12 weeks after surgery. Histological examination revealed a significant increase in the number of axons in injured sciatic nerve following exenatide treatment confirmed by stereomicroscopy. In an experimentally induced neurotmesis model in rats, exenatide had a positive effect on nerve regeneration evidenced by electromyography, functional motor tests, histological and stereomicroscopic findings., Competing Interests: Conflicts of interest: None declared.

Diabetes is a multisystem disorder and its effects are observed on the reproductive system. One of the main causes of testicular tissue damage is diabetes-induced overproduction of reactive oxygen species and glycated end products. The main objectives of this study were to investigate the possible effects of agomelatine (AG) and gallic acid (GA) in suppressing oxidative stress in Type I diabetes induced testicular damage. A total of 28 adult male rats were included in the study. Diabetes was induced by intraperitoneal injection of streptozocin (STZ, 55mg/kg) to 21 rats, which were then randomly assigned to 3 groups; 1mL saline solution was given to the diabetes+saline group by oral gavage, 20mg/kg/day oral AG was given to the diabetes+AG group, and 20mg/kg/day oral GA was given to the diabetes+GA group for 4 weeks. Tumor necrosis factor α (TNFα), nitric oxide synthase 2 (NOS2), fibronectin and vascular endothelial growth factor (VEGF) were used for the investigation of inflammation, fibrosis and vascular structures. The terminal-deoxynucleoitidyl-transferase mediated nick end-labeling assay (TUNEL) was used to detect apoptosis. Testicular tissue total antioxidant capacity values were tested by biochemical analysis. AG treatment showed an improvement on biochemical parameters and histopathological appearance on the rat testes. GA showed dose-related regenerative effects on biochemical parameters. Histologically, a minimal healing effect was determined on the testes damage. In conclusion, it was observed that AG is a potentially beneficial agent for reducing testicular damage by decreasing oxidative stress level. However, GA was seen to have a poor therapeutic effect., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Despite advances in understanding of peripheral nerve injuries and regeneration and advances in surgical techniques, successful outcomes cannot be guaranteed after reconstructive surgery. Platelet-rich plasma (PRP) has been reported to have positive effects on nerve regeneration, as well as on tissue healing. The present study was designed to evaluate the effect of PRP on nerve-grafted defects. Sprague-Dawley rats were divided into four surgery groups (n=7 in each). A 1-cm long nerve defect was created in the upper thigh and then reconstructed using a nerve autograft in all groups. The wet muscle weights, electromyographic findings, and histomorphologic changes were evaluated 10 weeks later. As shown by both the electromyographic (p<0.001) and histomorphologic findings (p<0.001), PRP had more positive effects on nerve gap reconstruction in Group 3 then Group 4 as compared to the control groups. The present study is novel in that it evaluated the regeneration effect of PRP on a large nerve defect reconstructed with a nerve graft rather than primary repair. The results are encouraging for further experimental studies on the role of PRP in nerve healing., (Copyright © 2016. Published by Elsevier Taiwan.)

Purpose: The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats., Materials and Methods: Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naïve control group and received no drug (n = 6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1 ml/kg saline or 80 μg/kg OT or 160 μg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed., Results: Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 μg/kg OT significantly improved EMG findings. OT treatment significantly lessened the thickening of perineural fibrosis when compared with saline group (p < 0.001). Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline-treated rats showed considerable increase in bax, caspase 3 and caspase 8 expressions (p < 0.001) while OT treatment significantly suppressed these apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to saline group., Conclusion: Present results demonstrate that OT appears to alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing inflammation, oxidative stress and apoptotic pathways.

Background: Although Alzheimer's disease (AD) is the most common age-related neurodegenerative disease and characterized by memory impairment, only symptomatic treatments are available., Objectives: Because recombinant human erythropoietin (rhEPO) has various neuroprotective effects and improves cognitive function in animal models of neurodegenerative disorders, we investigated the therapeutic effects of rhEPO in an intracerebroventricular (ICV)-streptozotocin (STZ) animal model of sporadic-AD., Material and Methods: A total of 24 Sprague-Dawley adult rats were divided into 4 groups of naive control (n = 6), sham-operated (n = 6), ICV-STZ + saline (n = 6) and ICV-STZ + rhEPO (n = 6). Twelve rats with Alzheimer's disease, induced by STZ injection (3 mg/kg) into both lateral ventricles using a stereotaxic frame (bilaterally ICV-STZ), were divided into 2 groups 5 days after the STZ injection: one treated with rhEPO 5000 (IU/kg/day, i.p.) and the other with 0.9% NaCl (1 mL/kg/day, i.p.) for 2 weeks. The sham-operated rats received bilaterally ICV-0.9% NaCl. No surgical operation or treatment was given to the naive-control animals. On day 20, a passive avoidance learning (PAL) test was used followed by sacrification and removal of the brain tissue in all animals. Brain TNF-α and ChAT levels were determined, and neurons in the hippocampal CA1 and CA3 regions were counted by Cresyl violet staining., Results: ICV-STZ was found to significantly shorten the latency time on the PAL, increase brain TNF-α level, and decrease brain ChAT activity and the number of neurons in the hippocampal CA1 and CA3 regions. On the other hand, rhEPO significantly attenuated all these detrimental effects induced by STZ., Conclusions: RhEPO treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and cholinergic deficit in rats. This result suggests that rhEPO may be beneficial for treating AD.

Cytokines, such as transforming growth factor (TGF)-ß1, and increased oxidative stress are considered to be responsible for the development of diabetic nephropathy. We hypothesized that Aesculus hippocastanum (AH) seeds may have preventive effects on oxidative stress and TGF-β-related diabetic nephropathy in streptozotocin (STZ)-induced diabetic nephropathy in rats. Twenty-one male Sprague-Dawley albino rats were divided into three groups (n=7). Except for the control group, they all had diabetic nephropathy induced by an intraperitoneal injection of STZ. While the diabetes group did not receive any medication, the diabetes+AH group was given the medication for 4 weeks. After the experiment, analyses were performed to evaluate the glomerular area, severity of sclerosis, and fibronectin immunoexpression, as well as levels of malondialdehyde (MDA), TGF-β, blood urea nitrogen (BUN), blood glucose, creatinine, and proteinuria. It was found that glomerular area, severity of sclerosis, fibronectin immunoexpression, and levels of MDA, TGF-β, BUN, creatinine, and proteinuria were decreased in the diabetes+AH group. It is known that diabetic nephropathy is induced, to a large extent, by hyperglycemia. In the present study, AH extract ameliorated diabetic nephropathy without decrease in blood glucose levels. In the study, AH seeds showed beneficial effects on the functional properties of the kidney and microscopic improvements in diabetic nephropathy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb-A), which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni), on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ). Forty-eight male rats were used. Twenty-four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racine's Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racine's Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose-dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb-A had been administered. For the groups that were administered Reb-A, the spike decrease was apparent in a dose-dependent manner, based on the spike percentage calculation. These results indicated that Reb-A has positive effects on PTZ-induced convulsions., (Copyright © 2016. Published by Elsevier Taiwan.)

Diabetic peripheral neuropathy (DPN) is widely considered as a degenerative complication of diabetic patients. The clinical effectiveness of folic acid (FA) on DPN is uncertain. The objective of the present study was to determine the effect of FA in DPN using electromyography (EMG), histopathological examination, immunohistochemistry, inclined plane test, and malondialdehyde (MDA) levels as a marker for lipid peroxidation in experimental diabetic rats. A total of 21 Sprague Dawley rats were randomly divided into 3 groups: control group, diabetes group, and FA-treated group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerve was lower in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerve was higher in the FA-treated group when compared with the diabetes group. Distal latency and CMAP duration in the sciatic nerve were lower in the FA-treated group when compared with the diabetes group. In histopathological examination of the sciatic nerve, peripheral fibrosis was present in the diabetic group; the fibrosis was lower in the FA-treated group. In comparison with the diabetes group, the expression of nerve growth factor (NGF) was higher in the FA-treated group. The scores for the inclined plane test were lower in the diabetes group and higher in the FA-treated group than the control group. The MDA levels were significantly lower in the FA-treated group when compared with the diabetes group.The study suggests that FA can protect diabetic rats against DPN and that the underlying mechanism for this may be related to improvement of the expression of NGF and lower MDA levels., (© The Author(s) 2013.)