Mesenchymal stem cells improve ischemic stroke injury by anti-inflammatory properties in rat model of middle cerebral artery occlusion

Background: Ischemic stroke is a major cause of permanent disability and inflammation has a prominent role in stroke pathology. Stem cell therapy is a new approach for stroke treatment. Mesenchymal stem cells (MSCs) are appropriate for this approach due to neuroprotective and immunomodulatory effects. Objectives: In this experimental study, the neuroprotective effects of mesenchymal stem cells (MSCs) on brain injury after transient middle cerebral artery occlusion (tMCAO) in rats was investigated with emphasis on inflammatory factors. Methods: Mesenchymal Stem Cells were isolated from bone marrow of rats and expanded by cell culture. Thirty-six male Wistar rats were randomly selected and divided to 6 groups. The MCAO model was performed in 4 groups with 24 and 72 hours of reperfusion. A single infusion of 2 × 106 MSCs was transplanted in one of the 24-hour and 72-hour groups and others received saline. In the sham groups, surgery was done without MCAO. Behavioral tests were evaluated and infarct volume was measured by staining of brain sections. Serum levels of Interleukin (IL) 1β and Tumor necrosis factor (TNF) α were measured by the enzyme linked immunosorbent assay (ELISA). Relative expression of Interleukin (IL)1β, tumor necrotizing factor (TNF)α, and IL6 genes were assessed in penumbra of the ischemic region using real time polymerase chain reaction (PCR). Results: The study results indicated that total behavioral scores were increased 72 hours after MSC transplantation (14.5 ± 2.0, P < 0.01). Moreover, MSCs decreased the infarct volume both 24 hours (18.82 ± 1.58, P < 0.01) and 72 hours (14.4 ± 1.53, P < 0.05) after MCAO. Serum levels of IL-1β and TNFα were increased after MCAO, yet MSCs transplantation decreased IL-1β (368.3 ± 109.5, P < 0.001) and TNFα (126.9 ± 38.6, P < 0.01) compared to saline. Also, relative gene expression of IL1β, TNFα, and IL6 was decreased by MSCs transplantation (P < 0.05). Conclusions: The MSCs had a neuroprotective effect in ischemic stroke via modulation of inflammatory response, and serum levels of IL1β and TNFα could be used as markers for evaluating anti-inflammatory effects of MSCs

Mesenchymal stem cells improve ischemic stroke injury by anti-inflammatory properties in rat model of middle cerebral artery occlusion

Background: Ischemic stroke is a major cause of permanent disability and inflammation has a prominent role in stroke pathology. Stem cell therapy is a new approach for stroke treatment. Mesenchymal stem cells (MSCs) are appropriate for this approach due to neuroprotective and immunomodulatory effects. Objectives: In this experimental study, the neuroprotective effects of mesenchymal stem cells (MSCs) on brain injury after transient middle cerebral artery occlusion (tMCAO) in rats was investigated with emphasis on inflammatory factors. Methods: Mesenchymal Stem Cells were isolated from bone marrow of rats and expanded by cell culture. Thirty-six male Wistar rats were randomly selected and divided to 6 groups. The MCAO model was performed in 4 groups with 24 and 72 hours of reperfusion. A single infusion of 2�106 MSCs was transplanted in one of the 24-hour and 72-hour groups and others received saline. In the sham groups, surgery was done without MCAO. Behavioral tests were evaluated and infarct volume was measured by staining of brain sections. Serumlevels of Interleukin (IL) 1βand Tumornecrosis factor (TNF)αwere measured by the enzymelinked immunosorbent assay (ELISA). Relative expression of Interleukin (IL)1β, tumor necrotizing factor (TNF)α, and IL6 genes were assessed in penumbra of the ischemic region using real time polymerase chain reaction (PCR). Results: The study results indicated that total behavioral scores were increased 72 hours after MSC transplantation (14.5±2.0, P &lt; 0.01). Moreover, MSCs decreased the infarct volume both 24 hours (18.82 ± 1.58, P &lt; 0.01) and 72 hours (14.4 ± 1.53, P &lt; 0.05) after MCAO. Serum levels of IL-1βand TNFαwere increased afterMCAO, yet MSCs transplantation decreased IL-1β(368.3±109.5, P &lt; 0.001) and TNFα (126.9 ± 38.6, P &lt; 0.01) compared to saline. Also, relative gene expression of IL1β, TNFα, and IL6 was decreased by MSCs transplantation (P &lt; 0.05). Conclusions: The MSCs had a neuroprotective effect in ischemic stroke via modulation of inflammatory response, and serum levels of IL1β and TNFα could be used as markers for evaluating anti-inflammatory effects of MSCs. © 2018, Iranian Red Crescent Medical Journal

The protective effect of bone marrow mesenchymal stem cells in a rat model of ischemic stroke via reducing the C-Jun N-terminal kinase expression

Ischemic stroke is the main cause of disability and mortality worldwide. Apoptosis and inflammation have an important role in ischemic brain injury. Mesenchymal stem cells (MSCs) have protective effects on stroke treatment due to anti-inflammatory properties. The inhibition of the C-Jun N-terminal kinase (JNK) pathway may be one of the molecular mechanisms of the neuroprotective effect of MSCs in ischemic brain injury. Twenty-eight male Wistar rats were divided randomly into 3 groups. Except the sham group, others subjected to transient middle cerebral artery occlusion (tMCAO). Bone marrow MSCs or saline were injected 3 h after tMCAO. Sensorimotor behavioral tests were performed 24 and 72 h after ischemia and reperfusion (I/R). The rats were sacrificed 72 h after I/R and infarct volume was measured by TTC staining. The number of apoptotic neurons and astrocytes in the peri-infarct area was assessed by TUNEL assay. The morphology of cells was checked by Nissl staining, and the expression of p-JNK was detected by immunohistochemistry and Western blot. Behavioral scores were improved and infarct volume was reduced by MSCs 24 h and 72 h after tMCAO. TUNEL assay showed that neuronal apoptosis and astroglial activity in the penumbra region were reduced by MSCs. Also, Nissl staining showed lower neuronal apoptosis in BMSCs-treated rats compared to controls. JNK phosphorylation which was profoundly induced by ischemia was significantly decreased after MSCs treatment. We concluded that anti-apoptotic and anti-inflammatory effects of MSCs therapy after brain ischemia may be associated with the down-regulation of p-JNK. © 2019 Elsevier Gmb

Prenatal urban traffic noise exposure impairs spatial learning and memory and reduces glucocorticoid receptor expression in the hippocampus of male rat offspring

Introduction: Exposure to noise stress during early life may permanently affect the structure and function of the central nervous system. The aim of this study was to evaluate the effects of prenatal exposure to urban traffic noise on the spatial learning and memory of the rats' offspring and the expression of glucocorticoid receptors (GRs) in their hippocampi. Methods: Three g\roups of pregnant rats were exposed to recorded urban traffic noise for 1, 2 or 4 h/day during the last week of pregnancy. At the age of 45 days, their male offspring were introduced to the Morris water maze (MWM) for assessment of spatial learning and memory. The corticosterone levels were measured in the offspring's sera by radioimmunoassay, and the relative expression of glucocorticoid and mineralocorticoid receptors (MRs) in their hippocampi was evaluated via RT-PCR. Results: Facing urban traffic noise for 2 and 4 h/day during the third trimester of pregnancy caused the offspring to spend more time and to travel a larger distance than the controls to find the target platform. Analogously, these two groups were inferior to their control counterparts in the probe test. Also, prenatal noise stress elevated the corticosterone concentration in the sera of the rats' offspring and dose-dependently decreased the relative expression of the mRNA of both GRs and MRs in their hippocampi. Conclusions: Urban traffic noise exposure during the last trimester of pregnancy impairs spatial learning and memory of rat offspring and reduces GRs and MRs gene expression in the hippocampus

Prenatal urban traffic noise exposure impairs spatial learning and memory and reduces glucocorticoid receptor expression in the hippocampus of male rat offspring

Introduction: Exposure to noise stress during early life may permanently affect the structure and function of the central nervous system. The aim of this study was to evaluate the effects of prenatal exposure to urban traffic noise on the spatial learning and memory of the rats' offspring and the expression of glucocorticoid receptors (GRs) in their hippocampi. Methods: Three g\roups of pregnant rats were exposed to recorded urban traffic noise for 1, 2 or 4 h/day during the last week of pregnancy. At the age of 45 days, their male offspring were introduced to the Morris water maze (MWM) for assessment of spatial learning and memory. The corticosterone levels were measured in the offspring's sera by radioimmunoassay, and the relative expression of glucocorticoid and mineralocorticoid receptors (MRs) in their hippocampi was evaluated via RT-PCR. Results: Facing urban traffic noise for 2 and 4 h/day during the third trimester of pregnancy caused the offspring to spend more time and to travel a larger distance than the controls to find the target platform. Analogously, these two groups were inferior to their control counterparts in the probe test. Also, prenatal noise stress elevated the corticosterone concentration in the sera of the rats' offspring and dose-dependently decreased the relative expression of the mRNA of both GRs and MRs in their hippocampi. Conclusions: Urban traffic noise exposure during the last trimester of pregnancy impairs spatial learning and memory of rat offspring and reduces GRs and MRs gene expression in the hippocampus

Neuroprotective Effects of Oxytocin Hormone after an Experimental Stroke Model and the Possible Role of Calpain-1

Background Different mechanisms will be activated during ischemic stroke. Calpain proteases play a pivotal role in neuronal death after ischemia damage through apoptosis. Anti-apoptotic activities of the oxytocin (OT) in different ischemic tissues were reported in previous studies. Recently, a limited number of studies have noted the protective effects of OT in the brain. In the present study, the neuroprotective potential of OT in an animal model of transient middle cerebral artery occlusion (tMCAO) and the possible role of calpain-1 in the penumbra region were assessed. Methods Adult male Wistar rats underwent 1 hour of tMCAO and were treated with nasal administration of OT. After 24 hours of reperfusion, infarct size was evaluated by triphenyltetrazolium chloride. Immunohistochemical staining and Western blotting were used to examine the expression of calpain-1. Nissl staining was performed for brain tissue morphology evaluation. Results OT reduced the infarct volume of the cerebral cortex and striatum compared with the ischemia control group significantly (P < .05). Calpain-1 overexpression, which was caused by ischemia, decreased after OT administration (P < .05). The number of pyknotic nuclei in neurons increased dramatically in the ischemic area and OT attenuated the apoptosis of neurons in the penumbra region (P < .01). Conclusion We provided evidence for the neuroprotective role of OT after tMCAO through calpain-1 attenuation. Key Words Stroke tMCAO calpain-1 oxytoci

Neurosteroids and their receptors in ischemic stroke: From molecular mechanisms to therapeutic opportunities

Extensive progress has been made to understand the pathophysiology of stroke but it is still a major cause of mortality and disability worldwide. There are few strategies for the treatment of this disease and the use of thrombolytic tissue plasminogen activator is limited due to the narrow time window. However, the administration of neuroactive steroids could be considered as a potential treatment approach to decrease ischemia-induced lesions. Neurosteroids receptors play important roles in neuroprotection mediated by these hormones. Membrane and intracellular receptors are both involved in the protective effects of estrogen and progesterone on ischemic brain injury. The intracellular receptors often regulate the gene transcription while the membrane receptors act through modulation of signal transduction pathways. Besides, allopregnanolone acts as a potent positive modulator of the GABA receptor. Moreover, the neuroprotective effects of vitamin D and dehydroepiandrosterone (DHEA) are mediated through the binding to vitamin D receptor (VDR) and several intracellular and membrane receptors, respectively. Activation of VDR could affect various processes including apoptosis, calcium metabolism, oxidative stress, immune modulation, inflammation and detoxification, and DHEA can modulate neurogenesis, neuronal function, and mitochondrial oxidative capacity. The present study aimed to describe the neuroprotective roles of the aforementioned neurosteroids with a focus on their receptors against ischemic stroke. © 2020 Elsevier Lt

Stratigraghy and Identifying Boundaries of Mozduran Formation with Magnetite Method in East Kopet-Dagh Basin

Kopet-Dagh Mountain Range is located in the north and northeast of Iran. Mozduran Formation in the east of Kopet-Dagh is mainly composed of limestone, dolomite, with shale and sandstone interbedded. Mozduran Formation is reservoir rock of the Khangiran gas field. The location of the study was east Kopet-Dagh basin (Northeast Iran) where the deliberate thickness of formation is 418 meters. In the present study, a total of 57 samples were gathered. Moreover, 100 thin sections were made out of 52 samples. According to the findings of the thin section study, 18 genera and nine species of foraminifera and algae were identified. Based on the index fossils, the age of the Mozduran Formation was identified as Upper Jurassic (Kimmerdgian-Tithonian) in the east of Kopet-Dagh basin. According to the magnetite data (total intensity and RTP map), there is a disconformity (low intensity) between the Kashaf-Rood Formation and Mozduran Formation. At the top, where among Mozduran Formation and Shurijeh Formation, is high intensity and a widespread disconformity (high intensity)

Assessment of Lead and cadmium contamination and influencing factors in raw milk from regions of Hamadan province

Regarding the significance of harmful effects of heavy metals in human diet, this study aimed to investigate the concentrations of lead and cadmium in raw milk samples. To achieve this goal, a total number of 48 samples was collected from various regions of Hamadan province during April 2011. The samples were analyzed by atomic absorption spectroscopy. According to the results, the mean concentrations of lead and cadmium estimated at 4.48 and 3.21µg/kg, respectively which were below the approved level determined by WHO as well as FAO. Although, concentrations of Pb and Cd among the various sampling regions revealed a significant (

Gonadal steroids block the calpain-1-dependent intrinsic pathway of apoptosis in an experimental rat stroke model

Objectives: Apoptosis plays an important role in the progression of the ischemic penumbra after reperfusion. Estrogen and progesterone have neuroprotective effects against ischemic brain damage, however the exact mechanisms of neuroprotection and signaling pathways is not completely understood. In this study, we investigated the possible regulatory effects of a combined steroid treatment on extrinsic and intrinsic apoptotic signaling pathways after cerebral ischemia. Methods: Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (tMCAO) using an intraluminal filament technique for 1 h followed by 23 h reperfusion. Estrogen and progesterone were immediately injected after tMCAO subcutaneously. Sensorimotor functional tests and the infarct volume were evaluated 24 h after ischemia. Protein expression of calpain-1 and Fas receptor (FasR), key members of intrinsic and extrinsic apoptosis, were determined in the penumbra region of the ischemic brain using western blot analysis, immunohistochemistry, and TUNEL staining. Results: Neurological deficits and infarct volume were significantly reduced following hormone therapy. Calpain-1 up-regulation and caspase-3 activation were apparent 24 h after ischemia in the peri-infarct area of the cerebral cortex. Steroid hormone treatment reduced infarct pathology and attenuated the induction of both proteases. FasR protein levels were not affected by ischemia and hormone application. Conclusion: We conclude that a combined steroid treatment inhibits ischemia-induced neuronal apoptosis through the regulation of intrinsic pathways. © 2016 Informa UK Limited, trading as Taylor & Francis Group