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Objective(s): Diabetic nephropathy is one of the main causes of kidney failure in the end stage of diabetes worldwide. The present study was conducted with the aim of using the remote ischemic conditioning (RIC) method to prevent diabetic nephropathy.Materials and Methods: Diabetes was induced by high-fat diet (60%) and streptozotocin injection (35 mg/kg) in rats. RIC was performed by tightening a tourniquet around the upper thigh and releasing it for three cycles of 5 min of ischemia and 5 min of reperfusion daily for an 8-week duration. At the end of the experiment, serum and urine parameters were examined. Anti-oxidant enzymes and lipid peroxidation levels in the kidney were also determined along with histological examination. The expression levels of tumor necrosis factor-alpha and transforming growth factor beta genes were also evaluated. Results: Glucose, cholesterol, triglyceride, and HbA1c concentrations were not significantly reduced in the RIC group. On the other hand, serum creatinine, urea, and albumin levels decreased and increased in urine. Anti-oxidant enzymes did improve in the kidney significantly and the expression of tumor necrosis factor-alpha and transforming growth factor beta genes decreased significantly. Histopathological examination also showed that necrosis, epithelial damage, and leukocyte infiltration increased in the diabetic group and improved in the treatment group. Conclusion: The results of biochemical analysis, and enzymatic and histological examinations showed that although RIC could not reduce blood glucose and lipids, nevertheless it may delay the progression of diabetic nephropathy due to the presence of anti-inflammatory and anti-oxidant activities.

Background: Inflammation plays a major part in brain ischemia. Propolis is a polyphenol-rich hive product with a set of pharmaceutical properties. Objectives: This research aims to investigate the impact of water extracts of brown propolis (WEPs) on stroke outcomes and inflammatory responses in a rat model of permanent middle cerebral artery occlusion (MCAO). Materials & Methods: This experimental study was conducted in Rafsanjan, Iran, in 2017. WEPs were experimentally prepared from two regions in Iran. Gas chromatography–mass spectrometry and Folin–Ciocalteu assays were used to determine chemical portrayal and the total polyphenol content, respectively. A total of 66 male adult mice were divided randomly into the surgical sham, control (vehicle-treated), and four WEPs-treated animal groups. WEPs-treated groups received doses of 100 and 200 (mg/kg, IP) four times, and their behavioral tests, brain edema, infarct volume, and tumor necrosis factor-alpha (TNF-α) level were evaluated. Results: The samples were not significantly different in terms of the concentration of the total polyphenol content. Compared to the control, WEPs led to a substantial decrease in the TNF-α level (P

Background: In recent years, stroke and ischemia–reperfusion injury has motivated researchers to find new ways to reduce the complications. Although reperfusion is essential for brain survival, it is like a double-edged sword that may cause further damage to the brain. Ischemic postconditioning (IPostC) refers to the control of blood flow in postischemia–reperfusion that can reduce ischemia-reperfusion injuries. Materials and Methods: Articles were collected by searching for the terms: Ischemic postconditioning and neuroprotective and ischemic postconditioning and hyperperfusion. Suitable articles were collected from electronic databases, including ISI Web of Knowledge, Medline/PubMed, ScienceDirect, Embase, Scopus, Biological Abstract, Chemical Abstract, and Google Scholar. Results: New investigations show that IPostC has protection against hyperperfusion by reducing the amount of blood flow during reperfusion and thus reducing infarction volume, preventing the blood–brain barrier damage, and reducing the rate of apoptosis through the activation of innate protective systems. Numerous mechanisms have been suggested for IPostC, which include reduction of free radical production, apoptosis, inflammatory factors, and activation of endogenous protective pathways. Conclusion: It seems that postconditioning can prevent damage to the brain by reducing the flow and blood pressure caused by hyperperfusion. It can protect the brain against damages such as stroke and hyperperfusion by activating various endogenous protection systems. In the present review article, we tried to evaluate both useful aspects of IPostC, neuroprotective effects, and fight against hyperperfusion.

Objective(s): Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods: Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method.Results: CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P

Objective(s): The Ischemia/reperfusion (I/R) phenomenon has a critical role in brain injuries induced by some kinds of stroke. The current study investigates the effects of Coenzyme Q10 (Q10) on global cerebral I/R in rats. Materials and Methods: Fifty male Wistar rats were used in this study. The global cerebral I/R was induced by obstructing both common carotid arteries for 20 min and the animals were treated with Q10 (200 mg/kg; PO.) for 6 weeks. Depressive and anxiety-like behaviors were assessed using the elevated plus-maze and forced swimming test, respectively. Working and spatial learning and memory were assessed by the Y-maze continuous alternation task and Morris water maze. The brain tissues were evaluated for brain edema, brain-derived neurotrophic factor (BDNF) levels, and superoxide dismutase (SOD) activities. Results: Our results indicated that global cerebral I/R increased anxiety and depression-like behavior as well as reduced cognitive performance. Moreover, the levels of BDNF and activities of SOD are reduced in stroke animals. Chronic post-stroke treatment with Q10 decreased brain edema. Furthermore, Q10 administration reduced anxiety and depressive-like behavior as well as cognitive impairments in stroke animals. Q10 also increased the SOD activities and BDNF levels in the brain tissues of stroke animals. Conclusion: Finally, we can conclude that using Q10 supplementation may be beneficial against the global cerebral I/R complications.

Objective(s): Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats. Materials and Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated.Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P

Introduction: Memantine as N-Methyl-D-Aspartic Acid (NMDA) receptor antagonist is used in some neurological disorders. Moreover, memantine presents modulatory effects on the somatosensory information processing in healthy subjects. This study investigated the effects of memantine on electrophysiological properties of barrel cortex neurons in male rats. Methods: Single unit recording was used to evaluate the electrophysiological properties of barrel cortex neurons. The neural responses to the Principal Whisker (PW), Adjacent Whisker (AW), and combined displacement of two whiskers [20 ms Inter-Stimulus Intervals (ISIs)] were recorded before and 2 hours after memantine gavage (10 mg/kg). A Condition Test Ratio (CTR) was calculated for assessing inhibitory interactions. Results: Two hours after memantine gavage, neuronal ON and OFF responses to PW deflection were decreased. Furthermore, CTR for both ON and OFF responses was decreased following memantine administration. Conclusion: The current study demonstrated that memantine modified neural response properties in the rat barrel cortex.

Introduction: During menopause, which is a part of the aging process in women, the level of sex hormones decreases, which causes problems such as memory impairment and cognitive functions. One of the treatment options for these disorders is hormone therapy, which has several side effects. The present study investigated the effect of remote ischemic conditioning (RIC) technique on memory improvement, muscle strength, motor and balance function in ovariectomized rats. Methods: In the present experimental study, 24 Wistar female rats with an approximate weight of (170-220 g) were divided into three groups (n = 8) including, 1: control group, 2: ovariectomy group and 3: ovariectomy+ treatment group. Initially, the animals in the second and third groups underwent ovariectomy surgery. The RIC techniques were performed on treatment group of rats for two months. After that, memory, muscle strength, and motor and balance function were assessed in all groups. SPSS software (V21) and one-way analysis of variance were used for statistical analysis. Results: The result of this study showed that RIC technique significantly improved memory in the ovariectomy+treatment group in comparison with the ovariectomy group (P

Introduction: Aging is a complex process and is considered as a risk factor for many diseases such as hypertension, Alzheimer, cancer, depression and anxiety. Recently, it has been shown that metformin, an anti-diabetic drug, has important neurological effects such as preventing memory loss, stroke, anxiety, inflammation and seizures. Therefore, the aim of this study was investigating the effects of metformin on some cognitive factors in elderly male rats. Methods: 24 rats (22 months) were randomly divided into 3 groups (n=8). The first group was the control group that received water orally, the second group received metformin 1 mg/kg orally and the third group received metformin 10 mg/kg orally. After treatment for 40 days (once daily), behavioral tests, including Y-maze, elevated plus maze and depression test were performed on animals. Results were analyzed using GraphPad Prism version 6 and One-way ANOVA followed by Tukey-post hoc test. Results: The results of this study showed that metformin at a dose of 10 mg/kg significantly reduced anxiety (P

Introduction: Currently, there is no effective and comprehensive treatment for ischemic stroke. There is strong clinical evidence for the benefits of hypothermia in neuroprotection. Therefore, the present study aimed to determine the effect of mild non-invasive hypothermia by JZL-184 on behavioral improvement in stroke rats. Methods: This study was performed on 5 groups of male mice weighing 25-30 g. The groups were as follows: 1- Healthy group 2- Control group (Stroke) 3- Stroke + DMSO solvent 4- Stroke + Aspirin (40mg /kg) 5- Stroke + JZL-184 (16mg / kg) (n = 8 per group). The drugs were injected intraperitoneally immediately after the stroke. At the times before (time zero) and at 5, 24 and 48 h after stroke induction, body temperature, behavioral testing, including muscle strength and sensory-motor dysfunction were measured. Data were analyzed by SPSS version 18 software and Two-way ANOVA test (P ≤ 0.05). Results: JZL-184 decreased body temperature at 5, 24 and 48 hours compared to intact and control groups (p

Introduction: Stroke is one of the leading causes of death and disability worldwide. Propolis, a polyphenol-rich resinous product processed by honeybees from a variety of plant sources, has a set of biological activities. We investigated the neuroprotective effect of Iranian brown propolis (IBP) in a mouse model of permanent middle cerebral artery occlusion (MCAO). Methods: Experimentally, water extracts of propolis (WEPs) were obtained from Kerman (KeWEP) and Khorasan Razavi (KhWEP) provinces, Iran. The chemical characterization and total polyphenol content of WEPs were determined using the Folin–Ciocalteu assay and gas chromatography-mass spectrometry (GC-MS). Animals were divided into eight experimental groups including: sham, control, and three groups each of which KeWEP- and KhWEP-treated mice. The drugs were administered at doses of 30, 100 and 200 mg/kg, intraperitoneally (IP), during four different time points. Infarct volume and brain edema were measured at 48 h. Behavioral tests were evaluated at 4, 24 and 48-hour post stroke. Results: The total polyphenol content was 1100 and 1400 mg/L in KhWEP and KeWEP respectively. Compared to the control group, the doses of 100 and 200 mg/kg in both samples decreased infarct volume. Brain edema was also reduced in all treatment groups. The dose of 200 mg/kg in both samples and 100 mg/kg in the KeWEP-treated group significantly increased grasping ability. Sensory-motor function was improved in all groups, too. Conclusion: These results suggest that IBP may reduce ischemic brain injury by its neuroprotective effect on focal cerebral ischemia.

Objective(s): Ceftriaxone (Cef), a beta-lactam antibiotic, is accompanied by antioxidant and anti-inflammatory properties. It has been shown that Cef has beneficial effects on Alzheimer’s disease. In the current investigation, the effect of Cef in a mice model of aging was investigated. Materials and Methods: Forty male mice were equally aliquoted into four groups as follows: Control (as healthy normal animals), D-galactose (DG) group (treated with 500 mg/kg/day DG for 6 weeks), DG + Cef group (treated with DG plus Cef 200 mg/kg/day for 6 weeks), and Cef group (treated with Cef 200 mg/kg/day for 6 weeks). A battery of behavioral tests was done to evaluate age-related neurocognitive changes. The activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as the level of malondialdehyde (MDA) in the brain, were measured by biochemical methods. Also, to determine the brain damage, histopathological alterations in the hippocampus were measured using hematoxylin and eosin (H&E) staining. Results: Our results indicate that neurobehavioral dysfunctions of DG can be prevented by co-administration of Cef. We also found that Cef increases the activity of SOD, GPx, and CAT as well as decreasing the level of MDA in the brain of aged mice. Conclusion: Based on our findings, Cef declines neurocognitive dysfunctions in the DG-induced model of aging, possibly through its antioxidative properties.

Background and objectives: Menopause is associated with depression as well as emotional and memory disorders. Based on the anti-inflammatory and antioxidant effects of pistachio, its effect on depression, cognitive function, anxiety and physical power in ovariectomized mice was investigated. Methods: In the current study, fifty female mice were used. They were aliquoted into five groups: control, ovariectomy (OVX), ovariectomy + DMSO, ovariectomy +10 mg/kg pistachioextract and Ovariectomy +100 mg/kg pistachio extract. In order to prepare the required extract, pistachio nuts were powdered (100 g) and macerated in 1 L of ethanol (80%) for 72 h. Pistachio extract was used orally once a day in ovariectomized mice for sixty days. Anxiety, depression, working memory and physical power were evaluated by the Elevated plus-maze (EPM) test, Forced swimming test (FST), Y maze and swimming exhaustion test, respectively. Results: The results showed that extract of pistachio (more potentially at the dose of 100 mg/kg) decreased anxiety-like behaviors and depression; besides, increase in working memory and physical power was observed in the ovariectomized mice. Conclusion: The findings of the current investigation suggest that pistachio extract could be used as a potential strategy for the attenuation of ovariectomy-related manifestation

Objective(s): Previous studies have indicated that phytoestrogens induce estrogenic as well as anti-inflammatory effects, and they are found in high abundance in the extracts of some herbs such as Vitex Agnus Castus (VAC). Therefore, we investigated the effect of VAC extract on ovariectomized mice after the induction of permanent middle cerebral artery occlusion (PMCAO) model. Materials and Methods: In this study, 50 mice ranging from 25 to 35 g were divided into five experimental groups as follows: Control, VAC, Estrogen, Tamoxifen, and Tamoxifen-VAC. Animals were ovariectomized, and after 30 days of treatment, they were given PMCAO induction. Behavioral assessment (adhesive removal and wire hanging tests) was evaluated 24 hr, 48 hr, and one week after induction of stroke. The infarct volume, as well as serum levels of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10), were measured one week after stroke.Results: One week after stroke, in both VAC and estrogen groups, the infarct size reduced in comparison with the control group. Estrogen and VAC extract improved adhesive removal and wire hanging test, increased the level of IL-10, and decreased the level of MMP-9 compared with the control group. In addition, co-administration of tamoxifen and VCA extract had no significant effect on measured indices compared with control and tamoxifen groups. Conclusion: Based on our findings, VAC extract has neuroprotective properties and can reduce stroke injuries in PMCAO-induced ovariectomized mice via anti-inflammatory and estrogenic properties.

Objective(s): Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer’s disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. Materials and Methods: For induction of AD, amyloid-beta 1-42 (Aβ1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. Results: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals.Conclusion: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Objective(s): Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. Materials and Methods: Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Results: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. Conclusion: Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors.

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

The Achillea millefolium L. (Yarrow) is a common herb which is widely being used, worldwide. Achillea is being used for treatment of many disorders since centuries. It is considered safe for supplemental use and flavonoids such as kaempferol, luteolin and apigenin are of main constituents present in Achillea. Most of both antioxidant and anti-inflammatory properties of this herb have been attributed to its flavonoid content. Oxidative and inflammatory processes play important roles in pathogenesis of neurodegenerative diseases. Present review was aimed to review the latest literature evidences regarding application of Achillea and/or its three main flavonoid constituents on epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and stroke.

Context: Oxidative stress has a critical role in the development of physical fatigue and activation of matrix metalloproteinases-9 (MMP-9). Naringin (Nar) is a bioflavonoid that has antioxidant activity and suppresses MMP-9 expression. Objective: The present study evaluates the anti-fatigue activity of Nar on physical fatigue and serum MMP-9 concentration in rats. Materials and methods: Fifty female Wistar rats were randomly divided into five groups (n = 10); a control group, vehicle group and three Nar treatment groups. The Nar treated groups received different doses of Nar (40, 80 and 160 mg/kg/day) for 30 days. On the 30th day, rats were sacrificed immediately after exhaustive swimming test. Serum MMP-9 concentration and several biochemical parameters related to fatigue were measured. Results: Exhaustive swimming time in the Nar-80 group significantly increased 1.78-, 1.53-, 1.5- and 1.3-fold compared with the control, vehicle, Nar-40 and Nar-160 groups, respectively. In addition, exhaustive swimming time in the Nar-160 group significantly increased 1.36-fold compared with the control group. Nar-80 significantly decreased LDH activity by 60.45% and 57.47% compared with the vehicle and control groups, respectively. Furthermore, Nar-80 and Nar-160 increased blood glucose levels by 19.56% and 18.38% compared with the control group, respectively. Nar-80 and Nar-160 significantly decreased serum MMP-9 concentration by 61.57% and 83.39% compared with the control group, respectively. Conclusion: Based on our data, Nar has anti-fatigue effects which may be attributed to its property in modulating energy metabolism and reducing serum MMP-9 concentration. Thus, Nar may be a promising agent for the treatment of physical fatigue.

Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. . Previous studies have referred to the effects of morphine on smooth and pulmonary muscles ., but the effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats. Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control (the mice were kept in their cages and received food and water), morphine receiving group, fatigue group (the mice in this group were kept running on a treadmill . for120 minutes at a rate of 20 meters per minute), and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase (LDH) and creatine phosphokinase (CPK). Results: Administration of morphine to the fatigue group decreased running time compared with the control group (P=0.009). Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH (P=0.009) and CPK (P=0.008). Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers (LDH, CPK).

Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for waterinsoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex.

Background & Aims: Stroke is the third leading cause of death. Oxidative stress has a principal role in the complications of stroke. Due to this fact and the antioxidant effects of ascorbic acid, this study was designed to evaluate the effect of ascorbic acid on reduction of stroke complications in a permanent model of middle cerebral artery (MCA) occlusion in male rats. Methods: In this experimental study, the rats were divided into 3 groups of control, ascorbic acid, and surgicalsham. Stroke wasinduced by cauterization of MCA. The animals' brain wassliced and stained using tetrazolium chloride (TTC) 48 hours after stroke induction. Then, infarction volume was determined using image processing software. In addition, behavioral tests, such as neurologic deficits, were evaluated 24 and 48 hours afterstroke induction. Data were statistically analyzed using One-way ANOVA test. Results: The infarct volume significantly reduced in the ascorbic acid treated group in comparison with control group (P < 0.010). Moreover, blood-brain barrier (BBB) breakdown, brain edema volume (P < 0.001), and the level of matrix metallopeptidase-9 (MMP-9) (P < 0.050) significantly reduced following treatment by ascorbic acid. Neurologic deficits, which were assessed using the Bederson Grading System, showed relative improvement in the ascorbic acid treated group (P < 0.050). Conclusion:Thisstudy showed that ascorbic acid, due to its neuroprotective effects, can significantly reduce the complications ofstroke.

Introduction: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormonedependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. Methods: 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. Results: The results demonstrated that VAC extract or estradiol had better performance on stepthrough passive avoidance test than control group (all P

Background and Aim: Oxidative stresses are involved in neuronal degeneration of substantia nigra and thereby induction of Parkinson's disease. It is reported that Foeniculum Vulgare L. can affect lactating and modulating dopaminergic system activity and antioxidant activity as well. In the present study, the effects of methanolic extract of Foeniculum Vulgare seeds on a Parkinson’s disease model induced by ICV injection of 6-hydroxydopamin (6-OHDA) in female rats were investigated. Materials and Methods: In this experimental study, 60 female rats were randomly divided into 6 equal groups including saline, Parkinson’s disease and Parkinson’s groups which were treated by different doses of the extract. Parkinson’s disease was induced by i.c.v injection of 6-OHDA. Methanolic extract of Foeniculum Vulgare seeds (100 and 200 mg/kg) was gavaged through two ways including repeated gavage (14 days before and 14 days after 6-OHDA injection) and acute gavage (once every day for 14 days after 6-OHDA injection). The induced Parkinson`s disease. was evaluated using Rotarod and Wire grasping tests on the day 14th after 6-OHDA injection. Results: The findings of the study demonstrated that repeated gavage of Foeniculum Vulgare extract improved motility and muscle tone in Parkinson’s animals (Pp

Objective(s):Hypothermia and decompressive craniectomy (DC) have been shown to be neuroprotective. This study was designed to evaluate neuroprotective effects of delayed singular or combination of DC and local hypothermia on stroke. Materials and Methods: Cerebral ischemia was induced in 48 Wistar rats assigned to 4 groups: control, decompressive craniectomy (DC), local hypothermia (LH), combination of hypothermia and craniectomy (HC). Infarct size and BBB disruption were measured 48 hr after ischemia insult. Neurological deficits were assessed at 24 and 48 hr after stroke by using sticky tape test, hanging-wire test and Bederson’s scoring system. BBB disruption was measured by Evans blue dye leakage. Results: Although infarct size was significantly reduced in LH, DC and HC groups (P

Background: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 (TRPV1) are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus. Methods: This study used four groups of rats. Two groups of rats (morphine and morphine+naloxone) received morphine based on the following protocol: 10 mg/kg (twice daily, 3 days) followed by 20, 30, 40 and 50 mg/kg (twice daily), respectively, for 4 consecutive days. Another group received vehicle (1 ml/kg) instead of morphine given using the same schedule. The morphine+naloxone group of rats additionally received naloxone (5 mg/kg) at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis. Results: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in TRPV1 gene expression in the amygdala (P

Introduction: Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Methods: Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day) were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p

Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day) were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p

Increased levels of proinflammatory cytokines have been recorded after the onset of transient or permanent brain ischemia and are usually associated with exacerbation of ischemic injury. Embolic stroke model is more relevant to the pathophysiological situation in such patients, because the majority of ischemic injuries in humans are induced by old thrombi that originate from the heart and carotid arteries. Therefore, the aim of the present study was to investigate changes of inflammatory cytokines after embolic stroke. Rats were subjected to embolic stroke, induced by a natural old clot which was injected in Middle Cerebral Artery (MCA), or sham stroke, which the same volume of saline was injected into the MCA. At 48 h after stroke induction, the levels of 5 cytokines (IL-1α and β, IL-6, IFN-γ and TNF-α) were determined in 500 µg of total protein using the Bio-Plex Rat Cytokine Array (BioRad), according to the manufacturer’s instructions in ischemic and non- ischemic cortices. While stroke animals showed infarctions and neurological deficits, we did not observe any cerebral infarction and neurological deficits in sham-operated animals. The levels of IL-1α (p=0.000) and -β (p =0.004), IL-6 (p =0.008), TNF-α (p =0.000) and IFN-γ (p =0.044) were significantly increased compared to sham treated animals. The findings of the present study suggest that part of ischemic injury in the embolic stroke may be mediated through the increased levels of inflammatory cytokines.

Objective(s)Opioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA). Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05) at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05). ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

Objective(s)Previous studies have demonstrated that pretreatment with alpha-tocotrienol (α-TCT) can reduce ischemic damage in mice following middle cerebral artery (MCA) occlusion. It is also reported to decrease stroke-dependent brain tissue damage in 12-Lox-deficient mice and spontaneously hypertensive rats. In the present study, the neuroprotective effects of α-TCT and rosiglitazone (RGZ) at 3 hr after cerebral ischemia were investigated. Materials and MethodsStroke was induced by embolizing a preformed clot into the MCA. Rats were assigned to vehicle, α-TCT (1 or 10 mg/kg), RGZ and sham-operation. ResultsCompared to the control group, only RGZ decreased infarct volume (P

Abstract In patients affected with stroke, most ischemic episodes (80-90%) occur due to occlusion of middle cerebral artery (MCA). Background: Some of blood through femoral artery was withdrawn into a PE- 50 catheter and kept for 2 h in room temperature and 22 h at 4°C to allow old clot formation. Then the catheter was advanced 17 mm in the internal carotid artery until its tip was 1 to 2 mm away from MCA origin. 3-5 µl the preformed clot or 5 µl saline (for sham- operated animals) were injected. Behavioral deficits and seizure activities were recorded at 2, 24, and 48 hours after clot injection. Then the rats were decapitated to remove the brains and prepare them for Tetrazoliume chloride (TTC) staining and analyzing. Methods: When 3 or 5 µl clots were injected, infarct volume was 29.35±1.26% and 16.15±94% respectively (p