Electroacupuncture Ameliorates Cognitive Impairment and Regulates the Expression of Apoptosis-Related Genes Bcl-2 and Bax in rats with cerebral ischaemia-reperfusion injury

Background Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. Objective To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). Methods Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. Results The EA group had significantly decreased neurological deficit scores compared to the IR group (p<0.05). In the MWM test, significant differences in escape latency and route were observed between the EA and IR groups (p<0.05). Rats in the EA group performed better in the probe trial than those in the IR group (p<0.05). EA treatment markedly reduced the number of TUNEL-positive cells compared to the IR group (20.13±4.30% vs 38.40±3.38%; p<0.001). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the Bcl-2/Bax ratio was significantly increased in the EA group compared to the IR group (1.61±0.19 vs 0.50±0.05, p<0.01). Conclusions These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression.

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Electroacupuncture Ameliorates Cognitive Impairment through Inhibition of Ca2+-Mediated Neurotoxicity in a Rat Model of Cerebral Ischaemia–reperfusion Injury

Acupuncture in Medicine ◽

10.1136/acupmed-2016-011353 ◽

2018 ◽

Vol 36 (6) ◽

pp. 401-407 ◽

Cited By ~ 4

Author(s):

Yun Zhang ◽

Xiang Mao ◽

Ruhui Lin ◽

Zuanfang Li ◽

Jing Lin

Keyword(s):

Cognitive Impairment ◽

Rat Model ◽

Cerebral Ischaemia ◽

Infarct Volume ◽

Artery Occlusion ◽

Sprague Dawley ◽

Ischaemia Reperfusion Injury ◽

Tetrazolium Chloride ◽

Ischaemia Reperfusion ◽

Intracellular Ca

Background The hippocampus is vulnerable to severe damage after cerebral ischaemia–reperfusion (I/R) injury. This study aimed to explore the effect of electroacupuncture (EA) on cognitive impairment and its relationship with Ca2+neurotoxicity in a rat model of I/R injury induced by middle cerebral artery occlusion (MCAO). Methods 60 adult male Sprague-Dawley rats were randomly divided into three groups: control (sham surgery) group, untreated MCAO group and EA-treated MCAO+EA group. Rats in the MCAO and MCAO+EA groups underwent modelling of poststroke cognitive impairment by MCAO surgery. EA was performed for 30 min daily at GV20 and GV24 (1–20 Hz) for 1 week. The Morris water maze experiment was used to assess cognitive function. 2,3,5-triphenyl tetrazolium chloride staining was used to measure infarct volume. The intracellular Ca2+content in the Cornu Ammonis (CA)1 area of the hippocampus was assessed by laser confocal scanning microscopy. ELISA was performed to evaluate the concentration of glutamate (Glu) in the hippocampus, and the protein expression of two Glu receptors (N-methyl-D-aspartic acid receptor (NMDAR) 2A and NMDAR2B) were analysed by Western blotting. Results Compared with the untreated MCAO group, EA effectively ameliorated cognitive impairment (P=0.01) and shrunk the infarct volume (P=0.032). The content of intracellular Ca2+, Glu and NMDAR2B in the hippocampus was significantly raised by MCAO (P=0.031-0.043), while EA abrogated these effects. NMDAR2A was decreased by MCAO (P=0.015) but increased by EA (P=0.033). Conclusions EA had a beneficial effect on cognitive repair after cerebral I/R, and its mechanism of action likely involves a reduction of Ca2+influx via inhibition of Glu neurotoxicity and downregulation of NMDAR2B expression.

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Protective effect of dl-3n-butylphthalide preconditioning on focal cerebral ischaemia-reperfusion injury in rats

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2012.00649.x ◽

2013 ◽

Vol 25 (1) ◽

pp. 12-17 ◽

Cited By ~ 1

Author(s):

Pei-Lei Zhang ◽

Hai-Tao Lu ◽

Jun-Gong Zhao ◽

Ming-Hua Li

Keyword(s):

Protective Effect ◽

Reperfusion Injury ◽

Neurological Deficit ◽

Cerebral Ischaemia ◽

Sham Operation ◽

Focal Cerebral Ischaemia ◽

Vegf Expression ◽

Ischaemia Reperfusion Injury ◽

Ischaemia Reperfusion ◽

Infarction Volume

ObjectiveTo investigate the effect of dl-3n-butylphthalide (NBP) on the protection of cerebral tissue and possible mechanism on ischaemia-reperfusion injury, and to find out whether NBP therapy can extend the reperfusion window in an experimental stroke model in rats.MethodsSeventy-two Sprague-Dawley rats were randomly divided into sham operation, ischaemia-reperfusion and ischaemia-reperfusion with NBP groups. Focal cerebral ischaemia was induced using the modified intraluminal thread method and maintained for 2, 3 or 4 h. The ischaemia-reperfusion group received reperfusion immediately after ischaemia-reperfusion. The NBP group received intraperitoneal injection of NBP immediately after ischaemia, followed by reperfusion. The sham operation group received only injection of physiological saline. The cerebral infarction volume and neurological deficit were analysed, and vascular endothelial growth factor (VEGF) expression in brain tissues was visualised by immunohistochemistry.ResultsNBP treatment caused a significant decrease in both infarction volume and neurological deficit compared with the ischaemia-reperfusion group at corresponding time points in each (p < 0.05). In the NBP group, the infarction volume and neurological deficit did not change with different ischaemia times. The expression of VEGF was significantly decreased in the ischaemia-reperfusion group compared with the sham group (p < 0.01), while this change was partly prevented in the NBP group (p < 0.01). The expression of VEGF in brain tissue in both the NBP and ischaemia-reperfusion groups gradually decreased when the ischaemic period was prolonged.ConclusionNBP treatment has a protective effect against cerebral ischaemia; this possible mechanism maybe related to the VEGF expression and may extend the reperfusion window for subsequent salvage of cerebral ischaemia by reperfusion.

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Peripheral Circulation and Astrocytes Contribute to the MSC-Mediated Increase in IGF-1 Levels in the Infarct Cortex in a dMCAO Rat Model

Stem Cells International ◽

10.1155/2020/8853444 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Xiaobo Li ◽

Wenxiu Yu ◽

Yunqian Guan ◽

Haiqiang Zou ◽

Zhaohui Liang ◽

...

Keyword(s):

Corpus Callosum ◽

Blood Plasma ◽

Early Stage ◽

Peripheral Circulation ◽

Artery Occlusion ◽

Control Group ◽

Sprague Dawley ◽

Double Positive ◽

Peripheral Blood Plasma ◽

Cerebral Artery Occlusion

Background and Purpose. Previously, we found that insulin-like growth factor-1 (IGF-1) levels in the infarct cortex in the acute phase of distal middle cerebral artery occlusion (dMCAO) rats are increased by intravenous infusion of allogeneic mesenchymal stem/stromal cells (MSCs). CD68+ microglia and NeuN+ neurons are part, but not all, of the sources of IGF-1. The present study is aimed at exploring the respective contributions of brain endogenous Iba-1+ microglia, GFAP+ astrocytes, infiltrated neutrophils, lymphocytes and monocytes/macrophages, and peripheral circulation, to the increased IGF-1 level in the infarct cortex after MSC infusion. Materials and Methods. Ischemic brain injury was induced by dMCAO in Sprague-Dawley rats. The transplantation group received MSC infusion 1 h after dMCAO. Expression of IGF-1 in GFAP+ astrocytes, Iba-1+ microglia/macrophages, CD3+ lymphocytes, Ly6C+ monocytes/macrophages, and neutrophil elastase (NE)+ neutrophils was examined to determine the contribution of these cells to the increase of IGF-1. ELISA was performed to examine IGF-1 levels in blood plasma at days 2, 4, and 7 after ischemia onset. Results. In total, only 5-6% of Iba-1+ microglia were colabeled with IGF-1 in the infarct cortex, corpus callosum, and striatum at day 2 post-dMCAO. MSC transplantation did not lead to a higher proportion of Iba-1+ cells that coexpressed IGF-1. In the infarct cortex, all Iba-1+/IGF-1+ double-positive cells were also positive for CD68. In the infarct, corpus callosum, and striatum, the majority (50-80%) of GFAP+ cells were colabeled with ramified IGF-1 signals. The number of GFAP+/IGF-1+ cells was further increased following MSC treatment. In the infarct cortex, approximately 15% of IGF-1+ cells were double-positive for CD3. MSC treatment reduced the number of infiltrated CD3+/IGF-1+ cells by 70%. In the infarct, few Ly6C+ monocytes/macrophages or NE+ neutrophils expressed IGF-1, and MSC treatment did not induce a higher percentage of these cells that coexpressed IGF-1. The IGF-1 level in peripheral blood plasma was significantly higher in the MSC group than in the ischemia control group. Conclusion. The MSC-mediated increase in IGF-1 levels in the infarct cortex mainly derives from two sources, astrocytes in brain and blood plasma in periphery. Manipulating the IGF-1 level in the peripheral circulation may lead to a higher level of IGF-1 in brain, which could be conducive to recovery at the early stage of dMCAO.

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Pyrrolidine dithiocarbamate protects the small bowel from warm ischaemia/reperfusion injury of the intestine: the role of haem oxygenase

Clinical Science ◽

10.1042/cs20060119 ◽

2006 ◽

Vol 111 (6) ◽

pp. 373-380 ◽

Cited By ~ 12

Author(s):

Ismail H. Mallick ◽

Marc C. Winslet ◽

Alexander M. Seifalian

Keyword(s):

Reperfusion Injury ◽

Redox Status ◽

Artery Occlusion ◽

Zinc Protoporphyrin ◽

Pyrrolidine Dithiocarbamate ◽

Sprague Dawley ◽

Ischaemia Reperfusion Injury ◽

Ischaemia Reperfusion ◽

Group I ◽

Haem Oxygenase

IR (ischaemia/reperfusion) injury of the intestine occurs commonly during abdominal surgery. We have previously shown that PDTC (pyrrolidine dithiocarbamate), an HO-1 (haem oxygenase-1) donor, improves intestinal microvascular perfusion. In the present study, we have investigated the effects of PDTC on the intestinal microcirculation following IR (ischaemia/reperfusion) injury of the intestine. Male Sprague–Dawley rats (n=72) were randomly assigned to four groups (n=18/group): (i) sham-operated group, who underwent laparotomy without induction of IR of the intestine; (ii) IR group, who were subjected to 30 min of superior mesenteric artery occlusion and 2 h of reperfusion; (iii) PDTC+IR group, who received PDTC prior to IR; and (iv) ZnPP group, who received the HO-1 inhibitor ZnPP (zinc protoporphyrin) followed by procedures as in group (iii). The ileum was evaluated for changes in tissue cytochrome c oxidase redox status, RBC (red blood cell) dynamics and leucocyte–endothelial interactions. The expression of HO-1 in the ileal tissue was examined at the end of the reperfusion. PDTC significantly improved the intestinal tissue oxygenation, mucosal perfusion index and RBC velocity compared with the IR and ZnPP groups. PDTC also decreased the leucocyte–endothelial interactions (P<0.05 compared with the IR and ZnPP groups). PDTC induced the expression of HO-1, whereas ZnPP abolished this effect.

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Dental pulp stem cell‐derived exosomes alleviate cerebral ischaemia‐reperfusion injury through suppressing inflammatory response

Cell Proliferation ◽

10.1111/cpr.13093 ◽

2021 ◽

Author(s):

Song Li ◽

Lihua Luo ◽

Yan He ◽

Ruohan Li ◽

Yangfan Xiang ◽

...

Keyword(s):

Stem Cell ◽

Inflammatory Response ◽

Reperfusion Injury ◽

Cerebral Ischaemia ◽

Dental Pulp ◽

Ischaemia Reperfusion Injury ◽

Ischaemia Reperfusion ◽

Dental Pulp Stem Cell

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Abstract TP93: Topically Applied Adipose-derived Mesenchymal Stem Cell Treatment In Experimental Focal Cerebral Ischemia

Stroke ◽

10.1161/str.48.suppl_1.tp93 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

George Wong ◽

Keyword(s):

Stem Cell ◽

Cerebral Ischemia ◽

Mesenchymal Stem Cell ◽

Parietal Cortex ◽

Cerebral Artery ◽

Topical Application ◽

Artery Occlusion ◽

Morris Water Maze Test ◽

Control Group ◽

Cerebral Artery Occlusion

Background and purpose: Disability is common after severe stroke resulting from major cerebral artery occlusion despite adoption of prophylactic decompressive craniectomy. Experimental mesenchymal stem cell treatments are commonly administrated through systemic infusion, with limitations in dosage. In this study, the neuro-modulation effect of topical mesenchymal stem cells (MSCs) was tested in a rodent middle carotid artery occlusion (MCAO) model. Methods: Twenty-four hours after MCAO, craniotomy was made and 0.8 x 10 6 GFP-MSCs were topically applied to the ipsilateral parietal cortex (N=30). In the control group, saline were topically applied to the ipsilateral parietal cortex (N=30). Results: After topical MSC treatment, neurological assessments with Rotarod test (at days 3, 7, and 10) and Morris Water Maze test (at days 3, 7, and 14) were significantly better, as compared to the control group; the infarct volume was also smaller. MSCs were found in the penumbra of the infarct 3 days after topical application. In the PCR array analysis of the RNA extracted from penumbra cortex, topical application of MSCs changed 10 gene expressions in the penumbra at day 3 (fold change >1.25, p<0.05 after Bonferroni corrections for multiple comparisons). The seven up-regulated genes (Apoe, Ascl1, Efnb1, Mef2c,Nog,S100a6, B2m) involve neuronal migration, neuronal differentiation, neuronal cell fate determination, regulation of synaptic plasticity, axonogensis;, growth factors, and cell adhesion. Pax2, Pax3 and Th were downregulated. Pax2 and Pax3 are related to apoptosis. Both Apoe and Thl involve synaptic transmission. Conclusions: Topically applied MSCs reduced cerebral infarction volume and improved the neurological function from cerebral ischemia resulting from a major cerebral artery occlusion in a rodent experimental model.

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A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent StrokeModels

Translational Stroke Research ◽

10.1007/s12975-020-00848-3 ◽

2020 ◽

Author(s):

Yi Wang ◽

Jae H. Choi ◽

Mohammed A. Almekhlafi ◽

Ulf Ziemann ◽

Sven Poli

Keyword(s):

Ischemic Stroke ◽

Artery Occlusion ◽

Brain Cooling ◽

Sprague Dawley ◽

Total Blood ◽

Pilot Studies ◽

Stroke Treatment ◽

Stroke Models ◽

Cold Infusion ◽

Cerebral Artery Occlusion

Abstract Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat’s total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.

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