Publications by authors named "Mohammad Reza Bigdeli"

45 Publications

The Positive Effect of MiR1 Antagomir on Ischemic Neurological Disorders Via Changing the Expression of Bcl-w and Bad Genes.

Basic Clin Neurosci 2020 Nov-Dec;11(6):811-820. Epub 2020 Nov 1.

Department of Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

Introduction: MicroRNAs (miRNAs or miRs) are non-coding RNAs. Studies have shown that miRNAs are expressed aberrantly in stroke. The miR1 enhances ischemic damage, and a previous study has demonstrated that reduction of miR1 level has a neuroprotective effect on the Middle Cerebral Artery Occlusion (MCAO). Since apoptosis is one of the important processes in neural protection, the possible effect of miR1 on this pathway has been tested in this study. Post-ischemic administration of miR1 antagomir reduces infarct volume via bcl-w and bad expression.

Methods: Rats were divided into four experimental groups: sham, control, positive control, and antagomir treatment group. One hour after MCAO surgery, the rats were received intravenously (Tail vein) 0.1 mL Normal Saline (NS), 0.1 mL rapamycin, and 300 pmol/g miR1 antagomir (soluble in 0.1 mL normal saline) in control, positive control, and treatment group, respectively. Twenty-four hours after reperfusion infarct volume was measured. The expression of miR1, bcl-w, and bad were analyzed using real-time PCR in sham, control, and treated groups.

Results: Our results indicate that administration of miR1 antagomir reduces infarct volume significantly, it also decreases miR1 and bad expression while increases bcl-w expression.

Conclusion: Understanding the precise neuroprotective mechanism of miR1 antagomir can make it a proper treatment and an innovative approach for stroke therapy.
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http://dx.doi.org/10.32598/bcn.11.6.324.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019842PMC
November 2020

The neuroprotective effect of MicroRNA-149-5p and coenzymeQ10 by reducing levels of inflammatory cytokines and metalloproteinases following focal brain ischemia in rats.

Brain Res Bull 2021 Apr 27;169:205-213. Epub 2021 Jan 27.

Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

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.
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http://dx.doi.org/10.1016/j.brainresbull.2021.01.013DOI Listing
April 2021

Effect of Dimethyl Fumarate on the Motor Function and Spatial Arrangement of Primary Motor Cortical Neurons in the Sub-Acute Phase of Stroke in a Rat Model.

J Stroke Cerebrovasc Dis 2021 Apr 23;30(4):105630. Epub 2021 Jan 23.

Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Histomorphometry & Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105630DOI Listing
April 2021

The Effect of Allograft Transplantation of Sertoli Cell on Expression of NF-кB, Bax Proteins, and Ischemic Tolerance in Rats with Focal Cerebral Ischemia.

Iran J Pharm Res 2020 ;19(2):98-114

Department of Anatomy and Cell Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

One of the newest methods to reduce cerebral ischemia damages is cell therapy. The aim of this study is to evaluate the effect of Sertoli cell transplantation on ischemia-induced injuries in animal models of stroke. Rats were divided into four groups: transplant+ischemia, ischemia, sham, and control. Sertoli cells were separated from the other testis of rats and cultured. Unilateral Sertoli cell transplantation was performed in the right striatum by using stereotaxic surgery. For induction of brain ischemia, middle cerebral artery occlusion surgery was used 14 days after transplantation. By using western blotting method, expression of nuclear factor kappa (NF-кB) and Bax were evaluated. In this study, a remarkable decrease in neurological deficits, infection, blood-brain barrier permeability, and brain edema was observed in the cell transplant recipient group in comparison with the ischemia group. Probably, a reduction in inflammation (NF-кB factor) and apoptosis (Bax) following injection of Sertoli cells result in amelioration of ischemic damages induced by MCAO surgery.
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http://dx.doi.org/10.22037/ijpr.2020.15574.13189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667533PMC
January 2020

Evaluating the effect of transplanting umbilical cord matrix stem cells on ischemic tolerance in an animal model of stroke.

Neurol Res 2021 Mar 9;43(3):225-238. Epub 2020 Nov 9.

Anatomy Department, Shahid Beheshti University of Medical Sciences , Tehran, Iran.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1080/01616412.2020.1839698DOI Listing
March 2021

Alpha-pinene exerts neuroprotective effects via anti-inflammatory and anti-apoptotic mechanisms in a rat model of focal cerebral ischemia-reperfusion.

J Stroke Cerebrovasc Dis 2020 Aug 13;29(8):104977. Epub 2020 Jun 13.

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran; Inistitute for Cognitive and Brain Sciences, Shahid Beheshti University. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104977DOI Listing
August 2020

Effects of nicorandil on neurobehavioral function, BBB integrity, edema and stereological parameters of the brain in the sub-acute phase of stroke in a rat model.

J Biosci 2020 ;45

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

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.
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January 2021

Sustained release of silibinin-loaded chitosan nanoparticle induced apoptosis in glioma cells.

J Biomed Mater Res A 2020 03 11;108(3):458-469. Epub 2019 Nov 11.

Razi Herbal Medicines Research Center and Department of Physiology, Lorestan University, of Medical Sciences, Khorramabad, Iran.

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.
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http://dx.doi.org/10.1002/jbm.a.36827DOI Listing
March 2020

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat.

J Pharm Pharmacol 2019 Nov 16;71(11):1725-1733. Epub 2019 Sep 16.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1111/jphp.13164DOI Listing
November 2019

Pro-Apoptotic and Anti-Angiogenesis Effects of Olive Leaf Extract on Spontaneous Mouse Mammary Tumor Model by Balancing Vascular Endothelial Growth Factor and Endostatin Levels.

Nutr Cancer 2019 10;71(8):1374-1381. Epub 2019 May 10.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology , Shahid Beheshti University , Tehran , Iran.

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.
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http://dx.doi.org/10.1080/01635581.2019.1609054DOI Listing
July 2020

Optogenetic Stimulation of the Anterior Cingulate Cortex Ameliorates Autistic-Like Behaviors in Rats Induced by Neonatal Isolation, Caudate Putamen as a Site for Alteration.

Neuromolecular Med 2019 06 19;21(2):132-142. Epub 2019 Feb 19.

Institute for Cognitive and Brain Science, Shahid Beheshti University, Tehran, Iran.

Epigenetic agents, such as neonatal isolation during neurodevelopmental period of life, can change various regions of the brain. It may further induce psychological disorders such as autistic-like phenomena. This study indicated the role of chronic increased anterior cingulate cortex (ACC) output on alteration of caudate putamen (CPu) as a main behavior regulator region of the brain in adult maternal deprived (MD) rats. For making an animal model, neonates were isolated from their mothers in postnatal days (PND 1-10, 3 h/day). Subsequently, they bilaterally received pLenti-CaMKIIa-hChR2 (H134R)-mCherry-WPRE virus in ACC area via stereotaxic surgery in PND50. After 22 days, these regions were exposed to blue laser (473 nm) for six consecutive days (15 min/day). Then, behavioral deficits were tested and were compared with control group in the following day. Animals were immediately killed and their brains were prepared for tissue processing. Results showed that neonatal isolation induces autistic-like behaviors and leads to overexpression of NMDAR1 and Nox2-gp91 proteins and elevation of catalase activity in the CPu regions of the adult offspring compared with control group. Chronic optogenetic stimulation of ACC neurons containing (ChR2+) led to significant reduction in the appearance of stereotypical behavior and alien-phobia in MD rats. The amount of NMDAR1 and Nox2-gp91 expression and the catalase activity in CPu were reduced after this treatment. Therefore, autistic-like behavior seems to be related with elevation of NMDAR1 and Nox2-gp91 protein levels that enhance the effect of glutamatergic projection on CPu regions. Optogenetic treatment also could ameliorate behavioral deficits by modulating these protein densities.
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http://dx.doi.org/10.1007/s12017-019-08526-wDOI Listing
June 2019

Erythropoietin Pretreatment Effect on Blood Glucose and Its Relationship With Inflammatory Factors After Brain Ischemic-Reperfusion Injury in Rats.

Basic Clin Neurosci 2018 Sep-Oct;9(5):347-356. Epub 2018 Sep 1.

Department of Physiology and Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

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.
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http://dx.doi.org/10.32598/bcn.9.5.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360489PMC
September 2018

Effect of intravenous injection of antagomiR-1 on brain ischemia.

Mol Biol Rep 2019 Feb 1;46(1):1149-1155. Epub 2019 Feb 1.

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s11033-018-04580-yDOI Listing
February 2019

Inhibitory Effect of Extract on Tumor Growth and Metastasis in 4T1 Breast Cancer Model.

Iran J Pharm Res 2018 ;17(1):276-291

Department of Biology, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.

as a medical herb is used in liver disorders and relieving cancer pain. In the present study, the cytotoxic, antioxidant, and anti-metastatic properties of hydro-alcoholic extract (VOE) were investigated in 4T1 breast cancer model. After treatment of 4T1 breast cancer cells with VOE, cell viability was measured by MTT assay. The implanted mice were treated with different concentration of VOE (50, 150 and 250 mg/kg) for 21 days. Levels of lactate dehydrogenase (LDH), γ -glutamyl transferase (GGT), alkaline phosphatase (ALP), carcinoembryonic antigen (CEA) and cancer antigen 15-3(CA15-3) in serum, and also catalase (CAT) and superoxide dismutase (SOD) activities in tumor tissue were measured. Metastatic rate was investigated in liver, spleen and lung tissues. VOE decreased cell viability of 4T1 cells, significantly. VOE significantly inhibited the cell proliferation, but not vasculature in the tumors that revealed by immunohistochemical analysis for Ki-67 and CD31 expression, respectively. VOE increased the Bax/Bcl-2 ratio in VOE250-treated group compared to control group. Serum analysis showed that treatment with 250 mg/kg of VOE significantly reduced LDH (not ALP and GGT) levels compared to controls. No linear correlation was found between the values of CEA and CA15-3 with tumor size. The rate of CAT activity was increased in VOE250-treated rats whereas, CAT and SOD activities were reduced in VOE50 group. VOE250 significantly decreased the metastatic rate in liver and lung compared to the other doses of VOE. Consequently has cytotoxic effects on 4T1 cells and affects antioxidant activity and metastasis in breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937098PMC
January 2018

Therapeutic Potential of Pretreatment with Allograft Sertoli Cells Transplantation in Brain Ischemia by Improving Oxidative Defenses.

J Mol Neurosci 2018 Apr 17;64(4):533-542. Epub 2018 Mar 17.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, G.C., Evin St, Shahriary Square, Tehran, IR, Iran.

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.
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http://dx.doi.org/10.1007/s12031-018-1054-xDOI Listing
April 2018

High intensity exercise preconditioning provides differential protection against brain injury following experimental stroke.

Life Sci 2018 Aug 6;207:30-35. Epub 2018 Mar 6.

Department of Exercise Physiology, School of Physical Education and Sport Sciences, Shahid Beheshti University of Sciences, Tehran, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.lfs.2018.03.007DOI Listing
August 2018

Intra-cerebral cannabidiol infusion-induced neuroprotection is partly associated with the TNF-α/TNFR1/NF-кB pathway in transient focal cerebral ischaemia.

Brain Inj 2017 5;31(13-14):1932-1943. Epub 2017 Sep 5.

a Department of Physiology, Faculty of Life Sciences and Biotechnology , Shahid Beheshti University , Tehran , Iran.

Background: 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.

Method: 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.

Results: 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.

Conclusion: 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.

Abbreviations: CBD, cannabidiol; ANOVA, analysis of variance; PVDF, polyvinylidene difluoride; SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis; SEM, standard error of mean.
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http://dx.doi.org/10.1080/02699052.2017.1358397DOI Listing
July 2018

Correlation Between Cannabidiol-Induced Reduction of Infarct Volume and Inflammatory Factors Expression in Ischemic Stroke Model.

Basic Clin Neurosci 2017 Mar-Apr;8(2):139-146

Department of Physiology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran.

Introduction: Recent studies demonstrated that cannabidiol had neuroprotective property. There is some evidence about effective role of cannabidiol in reduction of ischemic damages. It has been reported that infarct size is influenced by various factors after MCAO, including inflammatory factors. The aim of the present study was to evaluate the effect of cannabidiol on infarction volume and correlation of infarct size with tumor necrosis factor receptor 1 (TNFR1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression.

Methods: Using stereotaxic surgery, guide cannula was implanted in the right lateral ventricle. Cannabidiol (50, 100, and 200 ng/rat) was injected through ntracerebroventricular (i.c.v.) route for 5 consecutive days . Then, the rats underwent 60 minutes of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion, the infarct volume in total, cortex, piriform cortex-amygdala (Pir-Amy), and striatum areas of hemisphere were assessed. The expression of inflammatory factors such as TNFR1 and NF-κB in these regions were also studied.

Results: The present results indicate that in the MCAO-induced cerebral ischemia, administration of cannabidiol (100 and 200 ng/rat) causes a significant reduction in infarction volume in comparison with the vehicle group. Also, there were significant correlations between decrease of regional infarct volume and TNFR1/NF-κB expression.

Conclusion: The results of this study indicate that cannabidiol reduced cerebral infarction possibly through diminishing TNFR1/NF-κB-induced neurotoxicity in transient focal cerebral ischemia.
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http://dx.doi.org/10.18869/nirp.bcn.8.2.139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440923PMC
May 2017

The Neuroprotective Effect of Rosemary ( L.) Hydro-alcoholic Extract on Cerebral Ischemic Tolerance in Experimental Stroke.

Iran J Pharm Res 2016 ;15(4):875-883

Department of Chemical Engineering, Medicinal Plants & Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.

The prevention of BBB breakdown and the subsequent vasogenic edema are important parts of the medical management of ischemic stroke. The purpose of this study was to investigate the ischemic tolerance effect of leaf hydro-alcoholic extract (RHE). Five groups of animals were designed: sham (underwent surgery without MCAO) and MCAO groups, the MCAO groups were pretreated orally by gavages with RHE (50, 75, and 100 mg/Kg/day), daily for 30 days. Two hours after the last dose, serum lipid levels were determined and then the rats were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Subsequently, brain infarct size, brain edema and Evans Blue dye extravasations were measured and neurological deficits were scored. Dietary RHE could significantly reduce cortical and sub-cortical infarct volumes (211.55 ± 24.88 mm. 40.59 ± 10.04 mm. 29.96 ± 12.19 mm. 6.58 ± 3.2 mm), neurologic deficit scores, cerebral edema (82.34 ± 0.42% . 79.92 ± 0.49% . 79.45 ± 0.26% vs. 79.30 ± 0.19%), blood-brain barrier (BBB) permeability (7.73 ± 0.4 μg/g tissue . 4.1 ± 0.23 μg/g tissue . 3.58 ± 0.3 μg/g tissue . 3.38 ± 0.25 μg/g tissue) in doses of 50, 75 and 100 mg/Kg/day as compared with the control group in the transient model of focal cerebral ischemia. Although pretreatment with RHE plays an important role in the generation of tolerance against cerebral I/R injury, further studies are needed to clarify the mechanism of the ischemic tolerance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316267PMC
January 2016

Time course of neuroprotection induced by normobaric hyperoxia preconditioning and angiogenesis factors.

Iran J Basic Med Sci 2017 Jan;20(1):67-74

Department of Physiology, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran; Institute for Cognitive and Brain Sciences, Shahid Beheshti University, G.C., Tehran, Iran.

Objectives: 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.
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http://dx.doi.org/10.22038/ijbms.2017.8097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5243977PMC
January 2017

Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia.

Eur J Pharmacol 2017 Jan 14;794:270-279. Epub 2016 Nov 14.

Department of Physiology, Biological Science Faculty, Shahid Beheshti University, Tehran, Iran. Electronic address:

Excitotoxicity and imbalance of sodium and calcium homeostasis trigger pathophysiologic processes in cerebral ischemia which can accelerate neuronal death. Neuroprotective role of cannabidiol (CBD), one of the main non-psychoactive phytocannabinoids of the cannabis plant, has attracted attention of many researchers in the neurodegenerative diseases studies. The present investigation was designed to determine whether cannabidiol can alleviate the severity of ischemic damages and if it is able to exert its anti-excitotoxic effects through sodium and calcium regulation. By using stereotaxic surgery, a guide cannula was implanted into the lateral ventricle. Cannabidiol (50, 100, and 200ng/rat; i.c.v.) was administrated for 5 consecutive days. After pretreatment, the rats were subjected to 60min of right middle cerebral artery occlusion (MCAO). After 24h, neurological deficits score, infarct volume, brain edema, and blood-brain barrier (BBB) permeability in total of hemisphere, cortex, piriform cortex-amygdala, and striatum were assessed. The expression of Na/Ca exchangers (NCXs) protein as an endogenous target in these regions was also studied. The present results indicate that administration of cannabidiol (100 and 200ng/rat) in the MCAO-induced cerebral ischemia caused a remarkable reduction in neurological deficit, infarction, brain edema, and BBB permeability in comparison with the vehicle group. Up-regulation of NCX2 and NCX3 in cannabidiol-received groups was also observed. These findings support the view that the reduction of ischemic injuries elicited by cannabidiol can be at least partly due to the enhancement of NCX protein expression and its cerebro-protective role in those cerebral territories supplied by MCA.
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http://dx.doi.org/10.1016/j.ejphar.2016.11.011DOI Listing
January 2017

Effects of Crocin Supplementation during In Vitro Maturation of Mouse Oocytes on Glutathione Synthesis and Cytoplasmic Maturation.

Int J Fertil Steril 2016 Apr-Jun;10(1):53-61. Epub 2016 Apr 5.

Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Embryology, Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran.

Background: Crocin is an active ingredient of saffron (Crocus sativus L.) and its antioxidant properties have been previously investigated. This carotenoid scavenges free radicals and stimulates glutathione (GSH) synthesis; consequently, it may protect cells against oxidative stress. The aim of this research is to protect oocytes from oxidative stress by the addition of a natural source antioxidant.

Materials And Methods: In the present in vitro experimental study, we collected cumulus oocyte complexes (COCs) from mouse ovaries of euthanized, 6-8 week-old female Naval Medical Research Institute (NMRI) mice. Oocytes were subjected to in vitro maturation (IVM) in the presence of either crocin (5 or 10 μg/ml), 5 mM buthionine-[S-R]- sulfoximine (BSO), or the combination of crocin plus BSO. Oocytes that matured in vitro in a medium without crocin or BSO supplements were considered as controls. Following 16-18 hours of IVM, matured oocytes (n=631) were fertilized by capacitated sperm from NMRI male mice, and cultured in vitro for up to 96 hours to assess preimplantation embryonic development. The levels of GSH in metaphase II (MII) oocytes after IVM (n=240) were also assessed by the 5, 5-dithio-bis (2-nitrobenzoic acid) (DTNB)-GSH reductase recycling assay.

Results: Supplementation of IVM media with 10 µg/ml crocin significantly (P<0.05) increased nuclear maturation, preimplantation development and GSH concentrations compared with the control group. Maturation of oocytes in IVM medium supplemented with BSO alone or the combination of 5 µg/ml crocin and BSO drastically decreased GSH concentrations and subsequently resulted in low rates of maturation, fertilization and blastocyst development. However, the combination of 10 µg/ml crocin with 5 mM BSO increased the level of nuclear maturation which was comparable to the control group.

Conclusion: Supplementation of IVM media with crocin can improve nuclear maturation rates and subsequent developmental potential of mouse oocytes. This may occur by its beneficial effect in increasing GSH concentrations in MII oocytes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845530PMC
http://dx.doi.org/10.22074/ijfs.2016.4769DOI Listing
April 2016

Normobaric Hyperoxia Preconditioning Induces Changes in the Brain Lipidome.

Curr Neurovasc Res 2015 ;12(4):353-62

Faculty of Biological Science, Shahid Beheshti University, G.C. Tehran, Iran.

Recent investigations have demonstrated that normobaric hyperoxia induces neuroprotection against ischemic injury. The aim of study was to determine the survey of HO (hyperoxia) preconditioning on brain lipidome.The animals were assigned into three groups, the first experimental group was exposed to 95% inspired HO for 4 h /day for six consecutive days. The second experimental group considered as the control group and was exposed to 21% oxygen as room air (RA) in the same chamber. The third group acted as sham, which was under the stress of surgery condition without ischemia. The first two groups were divided into 2 subgroups, intact (without any surgery) and middle cerebral artery occlusion- operated (MCAO). Twenty-four hours after exposure to hyperoxia, MCAO subgroups were subjected to 60 min of right middle cerebral artery occlussion. After 24 h reperfusion, infarct volume (IV) and neurological deficit score (NDS) were assessed in MCAO subgroup. Brain lipidomics were measured in the intact subgroup. Preconditioning with HO significantly reduced NDS and IV and elevated the level of phosphatidylethanolamine (PE), sphingomyelin (SM), cholesterol ester (CE), cholesterol (Chol), phosphatidylcholine (PC), triglyceride (TG) and cerebroside (CB) in the brain as compared with the control (sham and RA). HO preconditioning, significantly decreased the brain ceramide (Cer) and lyso- phosphatidylcholine (Lyso-PC or LPC) levels. Preconditioning with HO decreases brain ischemia injury via changes in brain lipidomics and significantly decreases the brain ceramides (CER).Although more studies are required to explain the mechanisms of time course of neuroprotection, HO preconditioning partly decreases brain ischemia injury via changes in brain lipidome.
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http://dx.doi.org/10.2174/1567202612666150819100746DOI Listing
June 2016

A comparative study of saffron aqueous extract and its active ingredient, crocin on the in vitro maturation, in vitro fertilization, and in vitro culture of mouse oocytes.

Taiwan J Obstet Gynecol 2014 Mar;53(1):21-5

Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Embryology, Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran.

Objective: Reactive oxygen species have effects on gamete quality and gamete interaction; they influence spermatozoa, oocytes, embryos, and their environment. In this study, we evaluated the antioxidant effect of different concentrations of saffron (Crocus sativus L.) aqueous extract (SAE) and its ingredient, crocin, on the improvement of in vitro maturation (IVM) and subsequent in vitro fertilization (IVF) and embryo development of mouse oocytes.

Materials And Methods: Cumulus oocyte complexes were collected from ovaries, and germinal vesicle oocytes were cultured in the presence of SAE and crocin. SAE was added at dosages of 5 μg/mL, 10 μg/mL, and 40 μg/mL; dosages of crocin were 50 μg/mL, 100 μg/mL, and 400 μg/mL. All dosages were added to maturation medium and a group without SAE or crocin was considered as the control group. Following IVM, metaphase II oocytes were fertilized and cultured in vitro in order to observe embryo development.

Results: Both SAE and crocin improved the rate of IVM, IVF, and in vitro culture. Addition of 40 μg/mL SAE to maturation medium significantly increased the rate of IVM, IVF, and in vitro culture (p < 0.05). Furthermore 100 μg/mL crocin significantly increased the IVM rate compared to the control group (p < 0.05).

Conclusion: Use of SAE during IVM can affect on IVM, IVF, and early embryo development in a dose-dependent manner. SAE appears to have a stronger effect than pure crocin.
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http://dx.doi.org/10.1016/j.tjog.2012.11.004DOI Listing
March 2014

Time course of neuroprotection induced by normobaric hyperoxia and NCX1 expression.

Brain Inj 2014 11;28(8):1127-34. Epub 2014 Apr 11.

Department of Physiology, Faculty of Biological Sciences, Shaheid Beheshti University , G.C., Tehran , Iran.

Background: The purpose of this study was to determine if normobaric hyperoxia (HO) pre-conditioning offers durable neuroprotection against cerebral ischaemia and its effects on NCX1 expression.

Methods: Rats were divided into two experimental groups. The first group was exposed to 95% inspired HO for 4 hours/day for 6 consecutive days (HO). The second group acted as control and was exposed to 21% oxygen in the same chamber. Each main group was sub-divided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) sub-groups. After 2, 5, 10 and 15 days from pre-treatment, MCAO-operated sub-groups were subjected to 60 minutes of right MCAO. After 24 hours reperfusion, neurologic deficit score and infarct volume were measured in MCAO-operated sub-groups. The NCX1 expression levels of core, penumbra and sub-cortex regions were assessed in sham-operated and intact sub-groups.

Results: Pre-conditioning with HO decreased neurologic deficit score and infarct volume, and increased expression of NCX1 in penumbra and sub-cortex. These effects of hyperoxia disappeared gradually during 15 days after pre-treatment.

Conclusions: Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO partly is associated with expression of NCX1 consistent with an active role in the genesis of ischaemic neuroprotection.
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http://dx.doi.org/10.3109/02699052.2014.896472DOI Listing
February 2015

Neuroprotection of dietary virgin olive oil on brain lipidomics during stroke.

Curr Neurovasc Res 2013 Aug;10(3):231-7

Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Recent studies suggest that dietary virgin olive oil reduces hypoxia-reoxygenation injury in rat brain. This study investigated the effect of pretreatment with different doses of dietary virgin olive oil on brain lipidomics during stroke. In this experimental trial, 60 male Wistar rats were studied in 5 groups of 12 each. The control group received distilled water while three treatment groups received oral virgin olive oil for 30 days (0.25, 0.5 and 0.75 ml/kg/day respectively). Also the sham group received distilled water. Two hours after the last dose, the animals divided two groups. The middle cerebral artery occlusion (MCAO) group subjected to 60 min of middle cerebral artery occlusion (MCAO) and intact groups for brain lipids analysis. The brain phosphatidylcholine, cholesterol ester and cholesterol levels increased significantly in doses of 0.5 and 0.75 ml/kg/day compare with control group. VOO in all three doses increased the brain triglyceride levels. VOO with dose 0.75 ml/kg increased the brain cerebroside levels when compared with control group. VOO pretreatment for 30 days decreased the brain ceramide levels in doses of 0.5 and 0.75 ml/kg/day (p<0.05). Although further studies are needed, the results indicate that the VOO pretreatment improved the injury of ischemia and reperfusion and might be beneficial in patients with these disorders and seems to partly exert their effects via change in brain lipid levels in rat.
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http://dx.doi.org/10.2174/15672026113109990007DOI Listing
August 2013

Ischemic tolerance induced by normobaric hyperoxia and evaluation of group I and II metabotropic glutamate receptors.

Curr Neurovasc Res 2013 Feb;10(1):21-8

Department of Physiology, Faculty of Biological Sciences, Shahid Beheshti University, GC, Tehran, Iran.

Preconditioning-induced ischemic tolerance is one of the most important mechanisms, responsible for the increased brain resistance after stroke. Recent studies over the past years have provided interesting insights into the molecular mechanisms of this neuroprotective phenomenon. In this research, we attempted to see changes in the expression of group I and II metabotropic glutamate receptors (mGluR I and II) following intermittent hyperoxia preconditioning. Rats were divided into five groups (hyperoxia-intact, hyperoxia-MCAO, room air-intact, room air- MCAO, room air-sham). Hyperoxia groups were exposed to 95% inspired O2 for 4 h/day and 6 consecutive days. Oxygen level in room air groups was %21. 48 hours after pretreatment, MCAO-operated groups were subjected to focal cerebral ischemia for 60 min. 24 hours after reperfusion, neurologic deficit score (NDS) and brain infarct volume (IV) were evaluated in MCAO-operated subgroups. Sham-operated and intact groups were used to assess expression of group I and II mGluR and glutathione (GSH) levels of core, penumbra and subcortex regions. The results of this study showed that preconditioning with intermittent HO decreased NDS and IV, increased GSH levels in subcortex, and upregulated mGluRs I and II significantly. Although additional studies will be required to further elucidate precise mechanism(s) of ischemic tolerance, it seems that intermittent HO may exert its protective effects in part through upregulation of mGluR I and II.
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http://dx.doi.org/10.2174/156720213804805981DOI Listing
February 2013

The neuroprotection effect of pretreatment with olive leaf extract on brain lipidomics in rat stroke model.

Phytomedicine 2012 Jul 15;19(10):940-6. Epub 2012 Jul 15.

Department of Physiology, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Tehran, Iran.

Background: Recent studies suggest that olive extracts suppress inflammation and reduce stress oxidative injury. We have attempted to determine the effect of dietary olive leaf extract (OLE) on brain lipidomics in rat stroke model.

Methods: Five groups, each consisting of 12 male Wistar rats, were studied. First and second groups (control, and sham) received distilled water, while three treatment groups received oral olive leaf extract (OLE) for 30 days (50, 75 and 100 mg/kg/day, respectively). Two hours after the last dose, each main group was subdivided to Middle cerebral artery occlusion-operated and intact subgroup for assessment of neuropathology (neurologic deficit scores and infarct volume), brain lipid analysis and brain glutathione levels, respectively.

Results: OLE increased the brain cholesterol ester, cholesterol, cerebroside and phosphatidylcholine levels in doses of 50, 75 and 100 mg/kg/day. OLE increased the brain triglyceride levels in doses of 75 and 100 mg/kg/day and OLE reduced the brain ceramide levels in doses of 50, 75 and 100 mg/kg/day in comparison to the control group (p<0.05).

Conclusion: Although further studies are needed, it seems that the mechanism of OLE-induced ischemic tolerance in rats is partly associated with changes in brain lipids level.
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http://dx.doi.org/10.1016/j.phymed.2012.06.003DOI Listing
July 2012

Time course of neuroprotection induced by normobaric hyperoxia in focal cerebral ischemia.

Neurol Res 2012 Jun 20;34(5):439-46. Epub 2012 Mar 20.

Shahid Beheshti University, GC, Tehran, Iran.

Background: The purpose of this study was to determine if normobaric hyperoxia (HO) preconditioning offers durable neuroprotection against cerebral ischemia and the role of reactive oxygen species in the ischemic tolerance mechanism.

Materials And Methods: Rats were divided into four experimental main groups. First main group which was comprised four subgroups, were exposed to 90% HO for 6 days, 4 hours per day and subjected to 60 minutes of right middle cerebral artery occlusion (MCAO) after 2, 5, 10, and 15 days. Second group acted as control, was exposed to 21% oxygen (RA; room air) in the same chamber, and subjected to 60 minutes of right MCAO. Third main group comprised two subgroups, were exposed to 90% HO for 6 days, 4 hours per day, received normal saline (NS; 2HO+NS) and dimethylthiourea (DT) just before inhaling 90% HO (2HO+DT). Forth main group was exposed to 21% oxygen (2RA) in the same chamber and received normal saline (2RA+NS) and DT just before inhaling 21% oxygen (2RA+DT). Last two main groups were subjected to 60 minutes of right MCAO after 2 days. After 24-hour reperfusion, neurological deficit score (NDS), infarct volume, brain water content, and Evans blue extravasations were assessed in all animals.

Results: First main group compared with the RA group, NDS, infarct volume, Brain water content, and Evans blue extravasations were reduced in 2, 5, and 10 days significantly, whereas there was no difference among groups 2HO+DT, 2RA+DT, and 2RA+NS.

Conclusions: In the model of transient focal cerebral ischemia, hyperoxia preconditioning induced effective but transient neuroprotective effects.
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http://dx.doi.org/10.1179/1743132812Y.0000000013DOI Listing
June 2012

The role of protein kinase C in ischemic tolerance induced by hyperoxia in rats with stroke.

EXCLI J 2012 30;11:188-97. Epub 2012 Apr 30.

Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Recent studies suggest that normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion (IR) injury. Protein kinase C (PKC) is a key signaling molecule involved in protection against IR injury but its role in protective effect of HO in brain injury in unknown. In this study we attempted to see if PKC is involved in the effect of HO. Rats were divided into four main experimental groups. The first two were exposed to 95 % oxygen (HO) in a chamber 4 h/day for 6 consecutive days. Each of these groups had a control group exposed to 21 % oxygen. To investigate the role of PKC during HO, chelerythrin chloride (CHEL, 1 mg/kg/day), a PKC inhibitor, or its vehicle was given to animals for 6 days. After 24 h, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion neurological deficit scores, infarct volume, brain edema and blood-brain Barrier (BBB) permeability were assessed. HO decreased the infarct volume and brain edema in comparison with controls. PKC inhibition was associated with a significant increase in infarct size in both HO and control animals. PKC inhibition was unable to change brain edema in the experimental groups. Both HO and PKC inhibition reduced the BBB permeability within 24 h post occlusion of middle cerebral artery. Although both HO and PKC inhibition were associated with inhibition of BBB permeability during ischemic brain injury in rats, the neuroprotective effect of HO was independent of PKC in the MCAO model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932887PMC
July 2016