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Objectives Stroke exacts a heavy toll on death and disability worldwide. In animal studies, cell transplant has shown a positive effect by inducing neurogenesis, angiogenesis, and modulating inflammation. Cell transplant therapy could provide researchers with new strategies for treating stroke. The mechanistic target of rapamycin is a central signaling pathway for coordination and control; the administration of rapamycin, a key modulator of this pathway, could be a new therapeutic approach in neurological disorders. Materials and methods Adult rats were grouped into 5 main groups: control, sham, rapamycin receiving, Sertoli cell receiving, and rapamycin plus Sertoli cell receiving groups. Sertoli cells were taken from another rat tissue and injected into the right striatum region. After 5 days, ischemic induction was performed, and rapamycin injection (300 mg/kg) was performed 1 hour before surgery. After 24 hours, some regions of the brain, including the cortex, striatum, and piriform cortex-amygdala, were isolated for evaluation. Results Our results showed that infarct volume, brain edema, and blood-brain barrier permeability assessments were significantly reduced in some areas of the brain in rats that received rapamycin plus Sertoli cells compared with results shown in the control group. Conclusions Pretreatment with Sertoli cell transplant plus rapamycin injection may enhance neural survival during ischemia through increased glial cell-derived neurotrophic factor and vascular endothelial growth factor, inhibiting the mechanistic target of rapamycin pathway and increasing autophagy performance.

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreased rate of autophagy. Due to the many advantages, mesenchymal stem cells (MSCs), such as the secretion of neurotrophic factors, have been proposed for PD cell therapy. The present study, in continuation of the previous study, aimed to investigate the therapeutic effect of human-derived Conjunctival MSCs (CJ-MSCs) on the clearance of α-Syn by the microRNA-149(miR-149)/Akt/mTOR/ pathway.Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs were encapsulated, and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses evaluated the potency of CJ-MSCs (encapsulated and free cells) in PD rats. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed to investigate the expression of the miR-149-5p, Akt, mTOR, and α-Syn.Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. The gene expression evaluation showed a significant reduction in Akt, mTOR, and α-Syn mRNA levels and a significant increase in the level of miR-149-5p compared to the control group.It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by miR-149-5p/Akt/mTOR pathway and improve rats' motor functions.

Stroke, a cerebrovascular disease, has been introduced as the second cause of death and physical disability in the world. Recently, cell-based therapy has been considered by the scientific community as a promising strategy for reducing ischemic damages. The stem cells of the umbilical cord release growth and neurotrophic factors. The remarkable properties of these cells are the reason why they were selected as a potential candidate in the present research.In this study, the impact of transplanting umbilical cord stem cells on injuries resulting from ischemia was investigated. The male rats were categorized into three major. Using stereotaxic surgery, stem cells were injected to the right striatum of the brain. One week after transplantation, cerebral ischemic induction surgery was performed. The rats in the transplantation + ischemia group were separately divided into distinct sub-groups to explore the score of the neurological deficits, infarction volume, integrity of the blood-brain barrier, and brain edema.In this study, a significant decrease was observed in the neurological deficits of the transplantation + ischemia group compared with those of the control group. Similarly, the volume of infarction, the permeability of the blood-brain barrier, and edema were significantly reduced in the transplantation + ischemia group in comparison with those of the control group.The pretreatment of the transplanted umbilical cord stem cells in the striatum of ischemic rats possibly leads to restorative events, exerting a decreasing effect on cell death. Subsequently, these events may improve the motor ability and reduce ischemic injuries.

Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression.

The complex stroke pathophysiology, like oxidative stress and inflammatory reactions, causes substantially challenged in stroke treatment. Thymoquinone (TQ) is attributed to pharmacological actions like antioxidant and anti-inflammation. Thymoquinone is chemically hydrophobic, which causes poor solubility and bioavailability. To overcome this challenge Thymoquinone niosome was applied in this in-vivo study. The results demonstrated a significant reduction in rats treated with Thymoquinone niosome compared to free Thymoquinone and control groups (SOD), (TAC), and (GPX) activities were increased in the TQN group compared to the MCAO control group. The decrease in (MDA) level was seen in the Thymoquinone niosome group compared to the MCAO control group. The inflammation factors expression rates of IL-IB, IL-6, TNFα in I/R Thymoquinone niosome group were decreased. This study indicated that Thymoquinone niosome might be utilized as a promising novel carrier to improve Thymoquinone bioavailability and therapeutic effect in treating cerebral I/R injury.

Background and Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreases rated of autophagy. According to recent studies, cell therapy has been attracted much attention for PD treatment. Due to the many advantages mesenchymal stem cells (MSCs) have proposed, they have been considered a valuable resource for PD cell therapy. The present study aimed to investigate the therapeutic effect of Conjunctival MSCs (CJ-MSCs) on the autophagy manner and the expression of Mammalian target of rapamycin (mTOR), TH, and α-Syn in the parkinsonian rat model.Materials and Methods: our investigation has been performed using the Parkinson's model of rats. Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs both encapsulated and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses have been carried out to evaluate the potency of CJ-MSCs (both encapsulated and free cells) on PD rats. The Rotation, Rotarod Open field test was recruited as the behavioral tests. Immunohistochemistry was used to determine the tyrosine hydroxylase (TH), and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) has been performed for investigating the α-Syn and mTOR gene expression.Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. Immunohistochemistry analysis revealed an increase in the number of TH+ cells compared to the control group. The gene expression evaluation showed a significant reduction in mTOR and α-Syn mRNA levels than the control group. Our results also represented a significant difference between rats receiving encapsulated CJ-MSCs compared to the group received free CJ-MSCs.Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by reducing mTOR and thus increase TH expression that led improve the motor functions of rats. Our results indicated the CJ-MSCs as a suitable source of MSCs to reduce PD complications.

In this study, a chitosan nanoparticle formulation was synthesized for loading silibinin as a sustained-release drug system to evaluate its effects on apoptosis in C6 glioma cells. This synthesized nanoparticle was analyzed by measurement methods including Fourier transform infrared (FTIR), field emission-scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The formation and amorphization of nanoparticle were confirmed by FTIR and XRD analysis, respectively. The mean diameter of silibinin-loaded chitosan nanoparticles (SCNP) was 50 ± 7 and 188.6 ± 0.17 nm by using FE-SEM and DLS, respectively. In addition, the positive zeta potential of nanoparticles was +11.5. Rhodamine-conjugated SCNP analysis showed the internalization of silibinin to C6 glioma cells. The cytotoxicity assay indicated that the nanoformulation of silibinin was toxic to C6 glioma cells. Although SCNP significantly increased the expression of the both apoptotic genes in C6 cells, Bax and caspase3, it did not have any significant effect on the level of the antiapoptotic gene, Bcl2. In contrast, SCNP did not have any toxic effect on H9C2 cells. In conclusion, the results of the current study indicated that SCNP can be considered as a sustained-release drug system for future cell-based therapeutic strategies.

Objectives Oxidative stress and inflammation have a critical role in the pathogenesis of ischaemic stroke. Alpha-pinene is a monoterpenoid molecule with anti-inflammatory and antioxidant properties. The nobility of the present study was to evaluate the neuroprotective effect of α-pinene in ischaemic stroke. Methods Ischaemic stroke was induced by transient middle cerebral artery occlusion followed by 24 h reperfusion in male Wistar rats. Alpha-pinene (25, 50 and 100 mg/kg, i.p.) was administered in the beginning of reperfusion. Then, the neurobehavioural function, infarct volume, brain oedema, antioxidant enzyme activity and the concentration of malondialdehyde (MDA), nitric oxide (NO) and interleukin-6 (IL-6) were evaluated by different methods in the brain. Key findings Alpha-pinene (50 and 100 mg/kg) elicited a significant decrease in the brain oedema and infarct size as well as an improvement in the neurobehavioural function. Besides, α-pinene (100 mg/kg) restored the function of superoxide dismutase, catalase and glutathione peroxidase and reduced the concentration of MDA, NO and IL-6 in the hippocampus, cortex and striatum. Conclusions It was ultimately attainted that α-pinene exerts neuroprotective effect in ischaemic stroke in rat through the restoration of antioxidant enzymes activity, attenuation of lipid peroxidation and reduction of inflammation in the ischaemic brains.

Stroke is one of the leading causes of death in the world, but the underlying molecular mechanism of this disease remains elusive, thus it will be great challenges to finding appropriate protection. MicroRNAs are short, single-stranded, non-coding RNAs and recent studies have shown that they are aberrantly expressed in ischemic condition. Due to the fact that miR-1 has harmful effects on neural damages during brain ischemia, limited miR-1 has been proven to be protective in middle cerebral artery occlusion (MCAO). Here, the possible positive effect of intravenous injection of antagomiR-1 as a post-ischemic treatment on neurological deficits, infarct volume, brain edema and blood-brain barrier (BBB) permeability was evaluated. The rats were divided randomly into three experimental groups, each with 21 animals. MCAO surgery was performed on all groups and one hour later, 0.1 ml normal saline, 0.1 ml rapamycin and 300 pmol/g miR-1 antagomir (soluble in 0.1 ml normal saline), were injected intravenously into control, positive control and treatment group, respectively. After 24 h, neurologic deficits score, infarct volume, brain edema and BBB permeability were measured. The results indicated that post-treatment with miR-1 antagomir significantly improved neurological deficits and reduced infarction volume, brain edema, and BBB permeability. These data proved that there is a positive effects of antagomiR-1 on ischemic neuronal injury and neurological impairment. Due to the fact that microRNAs are able to protect the brain, it would be a promising therapeutic approach to stroke treatment.

Metal matrix composite (MMC) gears are used as a major component in the industry and are responsible for providing high-quality power transfer at high speeds. High quality, including high strength and impact-resistance, low brittleness, and long lifetime, is very important and needed in the industry. Gears are made of different materials, and, nowadays, researchers and industrialists have turned to designing, manufacturing, and using composite gears more than other gears due to their low weight, high hardness and strength, and better mechanical properties. In this research, the stress and strain behaviors are predicted in the composite gears made of aluminum silicon carbide with 3 different SIC volume fractions, namely 55 vol.%, 40 vol.%, and 30 vol.%, and with specifications of (Al45/SIC55, Al60/SIC40, and Al70/SIC30) and gears made of aluminum oxide with 3 different alumina weight fractions, namely 94 wt.%, 96 wt.%, and 99.5 wt.% to evaluate and compare the stress behavior due to different forces exerted on a single gear tooth in MMC gears. The Al45/SIC55 composite experienced the largest stress compared to other composites such as Al60/SIC40 and Al70/SIC30. The strain values (unlike the stress values) reduced with increasing in the volume fraction of the SIC reinforcement. Moreover, 94% aluminum oxide composite showed larger stress compared to 96% aluminum oxide and 99.5% aluminum oxide. The spur gear is designed and analyzed using SOLID WORKS and ANSYS Workbench softwares.

The increase in some factors following cerebral ischemia, especially Matrix metalloproteinase (MMPs) and inflammatory factors lead to blood-brain barrier (BBB) damages, edema and neuronal death. Previous studies have shown that these molecules are miRNA-149−5p (miR-149) and Coenzyme (Co) Q10 targets. Therefore, in this study, the effect of mimic of miRNA-149−5p (mimic miR) and CoQ10 on the expression of metalloproteinase 1 and 2 and inflammatory cytokines following injury caused by cerebral ischemia is investigated. Cerebral ischemia was modeled by Middle Cerebral Artery Occlusion (MCAO). Male Wistar rats were randomly divided into 6 groups: sham (without surgery and treatment), control (MCAO), negative control (NC): MCAO + scrambled miR, vehicle: MCAO + Ethanole, first treatment: MCAO + mimic miR, second treatment: MCAO + Q10. Each group was divided into 6 subgroups to evaluate neurological defects, the volume of tissue damage using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, blood-brain barrier permeability using cerebral Evans Blue (EB) staining, edema by measuring the percentage of brain water, MMP-2,9 mRNA and miR-149−5p levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the levels of IL-6 and TNF-α proteins using ELISA. The data obtained from this study showed that the use of mimic miR and Q10 increased the level of miR-149, decreased the extent of neurological defects and tissue damage, increased BBB integrity, decreased brain water percentage and also decreased the level of inflammatory cytokines and MMPs. It seems that the use mimic of miRNA-149−5p and Q10 can have a protective effect on the brain by reducing MMPs and inflammatory factors following cerebral ischemia and this could lead to a new treatment strategy to reduce the complications of cerebral ischemia.

Excitotoxicity and oxidative stress are central to the pathology of the nervous system, and inhibition of excitotoxicity induced by glutamate is one of the therapeutic goals determined for stroke. The present study aimed to investigate the effects of Astaxanthin, a potent natural antioxidant, on complications caused by acute cerebral stroke. In this research, 60 male Wistar rats were used which were divided into 5 groups as follow: (1) the sham group (vehicle), (2) the ischemic control group (vehicle), and the ischemic groups treated by Astaxanthin with doses of 25, 45, and 65 mg/kg. In the ischemic groups, ischemic model was performed by middle cerebral artery occlusion (MCAO) method, and the Astaxanthin administration was carried out after the artery occlusion and before opening the artery. The obtained results indicated that Astaxanthin could significantly reduce stroke volume, neurological deficits, and lipid peroxidation. Moreover, it was able to restore total oxidant status (TOS) and caspase 3 level to the normal level. The activity of antioxidant enzyme glutathione peroxidase (GPX), and the expression of catalase, GPx and nuclear factor kappa B (NFκb) genes, which were reduced after ischemia, were increased. This phenomenon was particularly pronounced for glutamate transporter 1 (GLT-1). Furthermore, Astaxanthin decreased the augmented pro-apoptotic gene Bax and restored the reduced Bcl2 expression to the normal level. Significant effects on the P53 and PUMA expression were not observed. Overall, the medium dosage of Astaxanthin appears to be more effective in reducing the complications of ischemia, particularly on our major study endpoints (stroke volume and neurological defects). Longer studies with a more frequent administration of Astaxanthin are required to better understand the precise mechanism of Astaxanthin.

Background: Spreading depolarization is associated with the extension of lesion size and complications in some important neurological diseases such as stroke, epilepsy, migraine, and traumatic brain injury. Objectives: This study aimed to reveal some molecular aspects of spreading depolarization and suggesting new therapeutic targets for its control by changing the function of different astrocytic and neuronal ion channels. Methods: The effects of nortriptyline on spreading depolarization in cortical and hippocampal tissues and on the electrophysiological properties of CA1 hippocampal pyramidal neurons were assessed by extra- and intracellular recording, following washing rat brain slices by the drug. Results: Nortriptyline made a significant increase in the amplitude of spreading depolarization in cortical and hippocampal tissues relative to control but did not change the duration significantly in each of the tissues. No significant difference was found in the effects of spreading depolarization on the electrophysiological properties of the CA1 pyramidal neurons between nortriptyline and control groups. Conclusions: The stimulating effect of nortriptyline on spreading depolarization is probably related to the augmentation of extracellular potassium collection in the cortex and hippocampus due to inhibition of astrocytic potassium scavenging function. This change can make more neurons prone to depolarization and increase the overall amplitude of spreading depolarization waves. Further studies should assess the effect of enhancing the clearance function of astrocyte-specific inwardly rectifying potassium channels, Kir4.1, or preventing other factors contributing to spreading depolarization on control of the process.

Blood-brain barrier (BBB) disruption, inflammation, and cell death are the pathogenic mechanisms of cerebral ischemia/reperfusion (I/R) injury. Nicorandil protects ischemic injury via some of these mechanisms. The aim of this study was to investigate the therapeutic effects of this drug on the brain ischemia after transient middle cerebral artery occlusion (MCAO) and clarify the NF-jB and Nrf2-dependent mechanisms modulated by this drug. Sixty-six rats were randomized into sham, MCAO and MCAO + nicorandil groups with oral gavage for 3 days. Cerebral I/R injury were induced by a transient MCAO for 1 h and neurobehavioral scores were performed for 3 days. In addition to measurement of BBB disruption and brain water content, the total and infarct volume, density, and total number of neurons, non-neurons and dead neurons in the right cortex were estimated by unbiased stereological methods. RT-PCR was performed to analyze the expression levels of NFjB and Nrf2. Although nicorandil treatment in the sub-acute brain ischemia did not have a prominent effect on neurobehavioral function and number of neurons, non-neurons and dead neurons probably through up-regulation of NF-jB, it, however, improved ischemia-induced BBB disruption and brain edema and showed a significant reduction in the infarction volume probably through up-regulation of Nrf2.

Background and Objective: Maternal separation as an epigenetic agent provokes a severe change in the brain, such as inflammation response, which is a key risk factor for the progression of autism spectrum disorders (ASD). This study evaluated the preventive effect of hypericin on maternal separation-induced cognitive deficits and hippocampal inflammation. Methods: Here, we reported that pups are subjected to maternal separations for 1 h per day from postnatal days (PND) 1-9 displayed apparent memory impairment in young rats (postnatal day 34) compared to controls group. Furthermore, maternal separation significantly increased inflammation factors in the hippocampus area. Anti-inflammation constituent shed light on treating ASD. Results: In this study, we found that treatment with hypericin (10 and 50 mg/kg) significantly suppresses expression of hippocampal interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the maternal separation rat model. Also, we found that hypericin prevented the decrease of hippocampal dopamine levels in the offspring of maternal separation rats. Conclusion: The data indicated that hypericin may play a neuroprotective role in hippocampal cell and ameliorates dysfunctions in memory and level of inflammation factor in this autism model. Thus, hypericin could be used as an intervention for treating ASD.

Background Ischemic stroke is a severe neurological disorder that affected millions of people worldwide. Neuro-inflammation and apoptosis play an essential role in the pathogenesis of neuronal death during ischemic stroke. Alpha-pinene is a bicyclic terpenoid with anti-inflammatory and anti-apoptotic activities. Accordingly, the main purpose of this study was to assess the protective effect of α-pinene in ischemic stroke. Materials and Methods To induce ischemic stroke in male Wistar rats, the middle cerebral artery was occluded for 60 min followed by 24 h reperfusion. Alpha-pinene was injected intraperitoneally at the beginning of reperfusion. A day after reperfusion, the neurological deficits, volume of infarct area, and blood-brain barrier (BBB) permeability were evaluated. The mRNA expression of inflammatory cytokines as well as pro- and anti-apoptotic genes was assessed by using reverse transcription-polymerase chain reaction. The protein levels of inflammatory cytokines were also measured by ELISA method. Results The results showed that α-pinene (50 and 100 mg/kg) significantly improved sensorimotor function and decreased the volume of infarct area in the brain. The high permeability of BBB was also alleviated by α-pinene (50 and 100 mg/kg) in ischemic areas. Besides, α-pinene (100 mg/kg) attenuated neuro-inflammation through decreasing both the gene and protein expression of TNF-α and IL-1β in the hippocampus, cortex, and striatum. Besides, α-pinene (100 mg/kg) suppressed apoptosis via downregulation of the pro-apoptotic Bax mRNA expression with a concomitant upregulation of anti-apoptotic Bcl-2 gene expression. Conclusions Overall, it was concluded that α-pinene exerts neuroprotective effect during ischemic stroke through attenuating neuroinflammation and inhibition of apoptosis.

Introduction: Introducing neurotrophic factors is among several new approaches to enhance neural resistance to ischemic condition. Cancer cells such as 4T1 (an invasive breast carcinoma cell line) are the most potent cells with high viability in transplanted area. The 4T1 cells are derived from spontaneous tumors in BALB/c mouse with their pathogenicity which is limited to this animal. Sertoli cells (SCs) can be a proper candidate for increasing the survival of transplanted cells. The SCs not only suppress the immune system, but also secret many growth factors which increase neural survival. The aim of this study was to evaluate the possible neuroprotective effect of 4T1 transplantation on middle cerebral artery occlusion (MCAO) rat model alone and in combination with SCs co-transplantation. Methods: Rats were categorized into 5 experimental groups as follows: control, sham, SCs, 4T1, and 4T1+SCs treated groups. For transplanting cells into right striatum, stereotaxic surgery was performed. In addition, ischemic surgery was induced after three days. Twenty-four hours after the reperfusion, neurological severity score (NSS), infarct volume, brain edema, and bloodbrain barrier (BBB) permeability were assessed in different areas of the brain including cortex, striatum, and piriform cortex-amygdala (Pir-Amy). Results: The SCs, 4T1, and SCs+4T1 cells co-transplantation ameliorated neurological deficits and reduced infarct volume, brain edema, and BBB permeability compared to the control group. Conclusion: Transplanting 4T1 cancer cell along with SCs as a source of neurotrophic factors enhanced neural survival providing a potential new approach in cell therapy.

Introduction: Brain Ichemic-Reperfusion Injury (IRI) activates different pathophysiological processes. It also changes physiological parameters such as Blood Glucose (BG) level. An increase in BG after stroke is associated with poor clinical outcomes. Erythropoietin has been shown to be effective on both reducing inflammation and BG level. Therefore, in this study the erythropoietin pretreatment effect on BG and its relationship with inflammatory markers after brain IRI was investigated. Methods: Thirty adult male Wistar rats were randomly divided into 5 groups: sham, control and 3 pretreatment groups: single dose, double dose, and triple dose that received 1000 U/kg of erythropoietin before stroke induction in different times intraperitoneally. A rat model of IRI was established by Middle Cerebral Artery Occlusion (MCAO) for 60 minutes. Infarct volume, neurological defects, Interleukin-1α (IL-1α) and IL-6 serum levels were evaluated 24 hours after reperfusion. Also BG was measured after 1, 6, and 24 hours. Results: Single dose of erythropoietin significantly decreased infarct volume and improved neurological defects which was associated with decreased serum level of IL-1α and IL-6 but higher doses of erythropoietin administration had adverse effects on histological, neurological, and inflammatory results. In addition, erythropoietin significantly increased BG in a dose- dependent manner. Conclusion: Erythropoietin could reduce brain IRI by reducing inflammation and BG stabilization. The results of the present study demonstrated a relationship between inflammatory factors and hyperglycemia after IRI and suggested that erythropoietin may be useful for preventing brain IRI, but its higher doses should be used with caution due to possible side effects.

Aims Different modes of physical activity provide cerebrovascular protection against thromboembolic events. Based on recent reports high intensity exercise protocols appear to raise cerebral VEGF levels leading to efficient cerebral angiogenesis. The present study aims to address if moderate continuous training (MCT) and high intensity interval training (HIT) differ in preconditioning against ischemic stroke. Methods Wistar rats were subjected to HIT or MCT for 8 weeks before transient middle cerebral artery occlusion (tMCAO) surgery. As indexes for improved angiogenic signals, VEGF-A and its pivotal receptor VEGF-R2 were immunoblotted just before occlusive stroke. Key findings Both training protocols induced a remarkable protection against neurological deficit and tissue injury following stroke. Cerebral infarctions were better improved in HIT animals which explained the slightly but not significantly higher neurological function. HIT brains developed higher levels of cortical VEGF-A and striatal VEGF-R2. Significance These data conclude preconditioning with high intensity protocols might excel continued moderate exercise to induce VEGF signaling and alleviate stroke outcomes. Further investigations may provide complementary mechanistic views.

Brain ischemia is one of the most common causes of death and disability worldwide, which usually happens through diminished blood supply to the tissue. Cell therapy and treatments using trophic factors are some of the new methods to protect brain cells against damage. Specific properties of Sertoli cells (SCs) make them suitable for improving neurological disorders. This study is to evaluate possible neuroprotective effects of SCs transplantation on ischemic damage. Rats were divided into three experimental groups including sham, control, and SCs-treated group. In this study, SCs were isolated from testis of rats and were transplanted into the right striatum by using stereotaxic surgery. After a week, ischemic surgery was performed. Twenty-four hours later, rats were scarified and different regions of the brain including the cortex, the piriform cortex-amygdala (Pir-Amy), and the striatum were collected and preserved in - 80 °C for further investigations. This study demonstrates that SCs transplantation can reduce brain ischemia deficits and increase superoxide dismutase (SOD) and catalase (CAT) activities. It also decreases malondialdehyde production, which is the main product of lipid peroxidation. SCs improve ischemic behavioral disorder and reduce brain edema, blood-brain barrier permeability, and infarct volume. It seems that transplantation of SCs can protect neural cells against ischemia by decreasing oxidative stress.

The aptamer based signal-on nanobiosensor for measuring salivary cortisol in the nanomolar level is presented for the first time in this study. Cortisol, as a stress biomarker, plays a critical role in physiological mechanisms. Measurement without contamination by needle stress is the main advantage of cortisol measurement in saliva. Salivary cortisol quantity is much lower than serum cortisol, so overcoming the measurement challenge requires new ultrasensitive detection methods. In the presented Target-Induced Structural Switching mode Aptamer (TISS) nanobiosensor, the ssDNA aptamer plays the role of transducer moiety and biorecognition module simultaneously. The aptamer structure has sequence against cortisol in the middle and two cytosine reach compartments in 3' and 5' ends which are designed for Ag-NC supramolecule configuration. The molecule-like properties of the Ag nanocluster create a strong AIE fluorescence signal. Binding aptamer to cortisol causes proximity of Ag-NCs supraparticles and leads to aggregation base fluorescence enhancement. 1 nmol/l as LOD and 1 nmol/L to 900 nmol/L for linearity achieved by presented salivary cortisol nanobiosensor. This assay was performed in one single tube without further stages as a mix and measure method.

Physical exercise contributes to improving stability against nerve injury caused by ischaemic stroke. Here we aimed to preliminarily investigate the effects of continuous endurance training (CET) and high-intensity interval training (HIT) on stroke-associated anxiety, locomotion, neurological assessments and P70S6 Kinase (P70S6K) activation as well. To do this, rats were trained according to HIT and CET protocols for 2 months prior to being subject to middle cerebral artery occlusion surgery.Twenty-four hours later behavioural examination was performed by elevated plus maze (EPM) testing, open field and neurological scoring followed by cortical and hippocampal P70S6Ks immunoblotting.According to the obtained data pre-ischaemic HIT and CET similarly improved neurological performance, anxiety levels and locomotion in EPM and open field tests following ischaemic stroke while there was a remarkable rise in hippocampal and cortical P70S6K activation in the HIT group compared to the CET counterparts.Behavioral and molecular data suggest that interval training is more beneficial rather than CET, but the distinct mechanisms of CET and HIT on memory are still topics to be discovered.

Stroke is a neurological disease, which, in addition to high mortality, imposes many financial and mental burdens on families and the society. The main objective of this study was to investigate the effect of cannabidiol (CBD) on one of the major inflammatory pathways in cerebral ischaemia.Using stereotaxic surgery, the cannula was implanted into the right lateral ventricle of rats. CBD (50, 100, and 200 ng/rat; i.c.v.) was administrated for five consecutive days. After pretreatment, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h, neurological deficits score, infarct volume, brain oedema, and blood-brain barrier (BBB) permeability in total, core, and penumbra areas were assessed. The expression of tumour necrosis factor alfa (TNF-α), tumour necrosis factor receptor 1 (TNFR1), and nuclear factor-kappa B (NF-кB) in the mentioned regions was also studied.Administration of CBD (100 and 200 ng/rat) caused a significant reduction in infarction, brain oedema, and BBB permeability compared with the vehicle-received group. Down-regulation of TNF-α, TNFR1, and NF-кB expression was also observed by CBD.The results achieved in this study support the idea that CBD has a cerebroprotective effect (partly through suppression of TNF-α, TNFR1, and NF-кB) on ischaemic injury.CBD, cannabidiol; ANOVA, analysis of variance; PVDF, polyvinylidene difluoride; SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis; SEM, standard error of mean.

Objective(s):Every year, a large number of people lose their lives due to stroke. Stroke is the second leading cause of death worldwide. Surprisingly, recent studies have shown that preconditioning with hyperoxia (HO) increases tissue tolerance to ischemia, ultimately reducing damages caused by stroke. Addressed in this study are beneficial contributions from HO preconditioning into reduced harm to be incurred by the attack, as well as its effect on the expression levels of vascular endothelial growth factor (VEGF) and endostatin. Materials and Methods: A set of experiments was conducted where a number of rats were divided into three groups. The animals in the first group received 90% oxygen for 4 hr a day, for 6 days. The second group was housed in room air and the third group was a sham (surgical stress). After 60 min of ischemia, 24 hr blood flow, neurological deficit score (NDS) and infarct volume (IV) in the group MCAO (Middle Cerebral Artery Occlusion) were investigated. Immediately following a 48 hr HO pre-treatment, sampling was performed to measure the expression levels of VEGF and endostatin. Results: Preconditioning with alternating HO led to reduced infarct volume and NDS. Moreover, pre-treatment with HO resulted in increased VEGF expression while decreasing endostatin. Conclusion: Although further studies are deemed necessary to clarify the mechanisms of ischemic tolerance, apparently, somewhat intermittent hyperoxia can be associated with positive impacts by increasing VEGF and decreasing expression of endostatin.

Objective: Choroid plexus epithelial cells (CPECs) have the epithelial characteristic, produce cerebrospinal fluid, contribute to the detoxification process in the central nervous system (CNS), and are responsible for the synthesis and release of many nerve growth factors. On the other hand, studies suggest that normobaric hyperoxia (HO) by induction of ischemic tolerance (IT) can protect against brain damage and neurological diseases. We examined the effect of combination therapy of encapsulated CPECs and HO to protect against ischemic brain injury. Materials and Methods: In this experimental study, six groups of adult male Wistar rats were randomly organized: sham, room air (RA)+middle cerebral artery occlusion (MCAO), HO+MCAO, RA+MCAO+encapsulated CPECs, HO+MCAO+encapsulated CPECs, RA+MCAO+empty capsules. RA/HO were pretreatment. The CPECs were isolated from the brain of neonatal Wistar rats, cultured, and encapsulated. Then microencapsulated CPECs were transplanted in the neck of the animal immediately after the onset of reperfusion in adult rats that had been exposed to 60 minutes MCAO. After 23 hours of reperfusion, the neurologic deficit score (NDS) was assessed. Next, rats were killed, and brains were isolated for measuring brain infarction volume, blood-brain barrier (BBB) permeability, edema, the activity of superoxide dismutase (SOD), and catalase (CAT) and also, the level of malondialdehyde (MDA). Results: Our results showed that NDS decreased equally in HO+MCAO, RA+MCAO+encapsulated CPECs, and HO+MCAO+encapsulated CPECs groups. Brain infarction volume decreased up 79%, BBB stability increased, edema decreased, SOD and CAT activities increased, and MDA decreased in the combination group of HO and transplantation of encapsulated CPECs in the ischemic brain as compared with when HO or transplantation of encapsulated CPECs was applied alone. Conclusion: The combination of HO and transplantation of encapsulated CPECs for stroke in rats was more effective than the other treatments, and it can be taken into account as a promising treatment for ischemic stroke.

It has been proven that olive associated products such as olive leaf extract (OLE) causes significant reduction in cancer cells viability and proliferation. Female BALB/c adult mice were divided into four groups. Three days prior to oral treatments, tumors were transplanted. First group were treated with distilled water and other three groups were received, respectively, 75, 150, and 225 mg/kg/day of OLE for three weeks. For assessment of anti-angiogenesis and pro-apoptotic effect of OLE on tumor tissue, tumor volume, cell mitosis and apoptosis, and also vascular endothelial growth factor (VEGF) and endostatin levels were assessed. OLE treatment with 150 and 225 mg/kg/day lead to significant reduction in tumor volume and cell mitosis compared with the control group, while the same doses significantly increase tumor cell apoptosis. OLE treatment with 150 mg/kg/day increase endostatin levels, while the same dose did not significantly decrease VEGF levels. The VEGF level is significantly reduced by the treatment with OLE 225 mg/kg/day for three weeks. Although, further studies are needed to clarify anti-angiogenesis and anti-apoptotic mechanism of OLE, consumption of OLE polyphenols after tumor transplantation reduced spontaneous mouse mammary tumor growth.

Background The therapeutic effects of dimethyl fumarate (DMF) in patients with multiple sclerosis and animal models of neurologic disease were reported. The density and the distribution pattern of motor neurons are important in transmitting the signal and controlling the movement-related functions. The present study evaluated the effects of DMF treatment on the neurological functions, infarct volume, and spatial distribution of the neurons in the primary motor cortex after cerebral ischemia. Methods Thirty-three Sprague-Dawley rats were randomly divided into three groups: The sham group underwent surgery without middle cerebral artery occlusion (MCAO) and drug. The vehicle and treatment groups after MCAO received a vehicle or DMF for three consecutive days. Post-stroke neurological and motor functions were assessed. At the end of the third day, the brains were removed, and the cerebral infarct volume was evaluated. We used cresyl violet staining to analyze the density and the spatial arrangement of motor cortical neurons using Voronoi tessellation. Results Treatment of the brain ischemia for three days with DMF could not significantly reduce the neurological and motor function deficits and infarct volume. However, it reduced the neuronal area and death and preserved their spatial distribution in the normal regular pattern. Conclusion Cerebral ischemia decreased the neuronal density of the primary motor cortex and changed their distributions to a random pattern. DMF treatment during sub-acute ischemic stroke did not significantly improve the neurological deficit scores. However, it could prevent neuronal swelling and death and preserved the spatial distribution of the cortical neurons in their normal pattern.

Stroke is the second leading cause of death worldwide. It is also the second rationale of disability, after Dementia. Interestingly, pre-conditioning can have a beneficial effect on stroke that increases ischemic tolerance in tissues. In this paper, we have shown that normobaric hyperoxia (HO) protects the rat brain from ischemia injury by changing in VEGF and endostatin levels. Animals were divided into three groups: the first group was exposed to 95% oxygen for 4 hours for 6 days, the second group was in room air, and the third group was sham. MCAO-operated were subjected to 60 minutes of MCAO. After 2 days from pre-treatment and 24 hours reperfusions, neurologic deficit score (NDS) and infarct volume (IV) were evaluated. We have measured VEGF and Endostatin levels of core, penumbra and sub-cortex regions. Pre-conditioning with HO decreased NDS (p