Remote Ischemic Postconditioning vs. Physical Exercise After Stroke: an Alternative Rehabilitation Strategy?

AbstractThere remain debates on neuroprotection and rehabilitation techniques for acute ischemic stroke patients. Therapeutic physical exercise following stroke has shown promise but is challenging to apply clinically. Ischemic conditioning, which has several clinical advantages, is a potential neuroprotective method for stroke rehabilitation that is less understood. In the present study, the rehabilitative properties and mechanisms of physical exercise and remote ischemic postconditioning (RIPostC) after stroke were compared and determined. A total of 248 adult male Sprague-Dawley rats were divided into five groups: (1) sham, (2) stroke, (3) stroke with intense treadmill exercise, (4) stroke with mild treadmill exercise, and (5) stroke with RIPostC. Focal ischemia was evaluated by infarct volume and neurological deficit. Long-term functional outcomes were represented through neurobehavioral function tests: adhesive removal, beam balance, forelimb placing, grid walk, rota-rod, and Morris water maze. To further understand the mechanisms underlying neurorehabilitation and verify the presence thereof, we measured mRNA and protein levels of neuroplasticity factors, synaptic proteins, angiogenesis factors, and regulation molecules, including HIF-1α, BDNF, TrkB, and CREB. The key role of HIF-1α was elucidated by using the inhibitor, YC-1. Both exercise intensities and RIPostC significantly decreased infarct volumes and neurological deficits and outperformed the stroke group in the neurobehavioral function tests. All treatment groups showed significant increases in mRNA and protein expression levels of the target molecules for neurogenesis, synaptogenesis, and angiogenesis, with intermittent further increases in the RIPostC group. HIF-1α inhibition nullified most beneficial effects and indicative molecule expressions, including HIF-1α, BDNF, TrkB, and CREB, in both procedures. RIPostC is equally, or superiorly, effective in inducing neuroprotection and rehabilitation compared to exercise in ischemic rats. HIF-1α likely plays an important role in the efficacy of neuroplasticity conditioning, possibly through HIF-1α/BDNF/TrkB/CREB regulation.

Download Full-text

Abstract WP272: A Powerful Combination Therapy for Stroke: Post-Ischemia Ethanol Administration and Normobaric Oxygenation on Ischemic Rats

Stroke ◽

10.1161/str.44.suppl_1.awp272 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Christopher Sy ◽

Xiaokun Geng ◽

Paul Fu ◽

Changya Peng ◽

Vance Fredrickson ◽

...

Keyword(s):

Combination Therapy ◽

Protein Expression ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Artery Occlusion ◽

Neurological Deficits ◽

Ethanol Administration ◽

Acute Administration ◽

Sprague Dawley ◽

Acute Cerebral Ischemia

Objectives: Normobaric oxygenation (NBO) has been reported to be neuroprotective against acute cerebral ischemia. Recently, a clinical trial was terminated because beneficial outcomes were not definitive. Our recent study ( Stroke. 2012 43(1):205-10 ) demonstrated a strong neuroprotective effect induced by acute administration of ethanol (EtOH) at 1.5g/kg. In this study, we assessed the therapeutic influence of EtOH in combination with NBO. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 2h. Ischemic animals received either an intraperitoneal injection of EtOH (1.0g/kg), a course of NBO (100% for 2h), or a combination of both immediately prior to reperfusion onset. Brain injury was determined by infarct volume and behavioral outcomes at 48h post-reperfusion. Metabolic dysfunction was investigated by assessing ADP/ATP ratios, reactive oxygen species (ROS) levels, NADPH oxidase (NOX) activity, and protein expression of NOX subunits (p47 phox , gp91 phox , and p67 phox ), as well as the protein expression and enzyme activity of pyruvate dehydrogenase (PDH), at both 3h and 24h after reperfusion. Results: Combination therapy led to a significant decrease in infarct volumes (Saline: 48±4%, EtOH: 38±3%, NBO: 37±4%, Combination: 19±3% ) and in neurological deficits (Belayev Scale 0-12, Saline: 8.4±0.7; EtOH: 6.5±0.7; NBO: 6.4±0.6; Combination: 4.4±0.3 ). At 3h and 24h post-reperfusion the decrease in ADP/ATP ratio was significantly enhanced, reflecting a preservation of cellular energy. A greater decrease in NOX activity and protein expression was observed, in association with decreased ROS levels, suggesting that improved glycolysis may contribute to neuroprotection. PDH activity and protein expression was dramatically increased, making the facilitation of aerobic metabolism a probable mechanism for preserving cellular ATP. Conclusions: Our findings demonstrate that a synergistic relationship exists between EtOH and NBO. Both are promising neuroprotective agents when used together, even at low doses. Moreover, both are inexpensive, widely available, easy to administer, and have little side effects. Thus, combination therapy could be an effective and efficient approach to future stroke treatments.

Download Full-text

Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

Journal of Applied Physiology ◽

10.1152/japplphysiol.01084.2017 ◽

2018 ◽

Vol 125 (1) ◽

pp. 49-57 ◽

Cited By ~ 3

Author(s):

Chun Li ◽

Hong Sun ◽

Guodong Xu ◽

Kimberly D. McCarter ◽

Jiyu Li ◽

...

Keyword(s):

Cerebral Ischemia ◽

Brain Damage ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neutrophil Infiltration ◽

Neurological Deficits ◽

Sprague Dawley ◽

Ischemic Brain Damage ◽

Mitochondrial Oxidative Stress ◽

Ischemic Brain

Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg−1·day−1) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg−1·day−1ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloproteinase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation.NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

Download Full-text

Neuroprotective Effects of Early Hypothermia Induced by Phenothiazines and DHC in Ischemic Stroke

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/1207092 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yun Han ◽

Xiao-kun Geng ◽

Hangil Lee ◽

Fengwu Li ◽

Yuchuan Ding

Keyword(s):

Ischemic Stroke ◽

Brain Damage ◽

Glucose Transporter ◽

Infarct Volume ◽

Neurological Deficits ◽

Ros Production ◽

Sprague Dawley ◽

Drug Induced ◽

Neuroprotective Effects ◽

Sprague Dawley Rats

Background and Purpose. Studies have shown that interischemia hypothermia is able to reduce the size of myocardial infarctions and improve their clinical outcomes. The present study determined whether interischemia hypothermia induced by the pharmacological approach induced stronger neuroprotection in ischemic brains. Methods. Adult male Sprague Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (interischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin (DHC) was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the interischemia and inter-reperfusion groups, brain damage was evaluated using infarct volume and neurological deficits at 24 h reperfusion. In addition, mRNA expressions of NADPH oxidase (NOX) subunits (gp91phox, p67phox, p47phox, and p22phox) and glucose transporter subtypes (GLUT1 and GLUT3) were determined by real-time PCR at 6 and 24 h reperfusion. ROS production was measured by flow cytometry assay at the same time points. Results. In both hypothermia groups, the cerebral infarct volumes and neurological deficits were reduced in the ischemic rats. At 6 and 24 h reperfusion, ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by interischemia hypothermia at 24 h. Conclusion. Both interischemia and inter-reperfusion pharmacological hypothermia treatments play a role in neuroprotection after stroke. Interischemia hypothermia treatment may be better able to induce stronger neuroprotection after ischemic stroke. This study provides a new avenue and reference for stronger neuroprotective hypothermia before vascular recanalization in stroke patients.

Download Full-text

Outcome in Acute Stroke with Different Intra-Arterial Infusion Rate of Urokinase on Thrombolysis

Interventional Neuroradiology ◽

10.1177/159101991001600311 ◽

2010 ◽

Vol 16 (3) ◽

pp. 290-296 ◽

Cited By ~ 8

Author(s):

X. Gan ◽

Y. Luo ◽

F. Ling ◽

X. Ji ◽

J. Chen ◽

...

Keyword(s):

Infusion Rate ◽

Infarct Volume ◽

Acute Stage ◽

Male Rats ◽

Neurological Deficits ◽

Sham Operation ◽

Sprague Dawley ◽

Arterial Infusion ◽

Doppler Flowmetry ◽

Sham Operation Group

Intra-arterial infusion of urokinase (UK) has been widely used. However, the optimal infusion rate of the reagent has never been determined. This was investigated in the acute stage of middle cerebral artery (MCA) embolism in the present study. Sprague Dawley male rats (n=43) were randomly divided into sham-operation and five ischemic groups with urokinase administration at different infusion rates or without urokinase administration. Ischemia was induced with MCA embolism. Two hours after embolism, total urokinase (urokinase, 170,000U/kg) was given in groups A,B,C and D (n=8 each) at different rates: 1,000 U (0.03 ml/min) per minute, 4,000U (0.12 ml/min), 10,000U (0.30 ml/min), and 16,000U (0.48 ml/min), respectively. Group E received normal saline at a rate of 0.48 ml/min. The sham-operation group (no embolism) received urokinase at (170,000U/kg, 1.5 ml, 16,000 U/min). During ischemia and thrombolysis, regional cerebral blood flow (CBF) was monitored by laser Doppler flowmetry. The neurological deficits, infarct volumes and mortalities in each group were determined. The CBF in ischemic hemisphere were significantly (p<0.05) decreased after embolism in groups A!E at similar levels (27.32±8.20% to 34.71±6.84%). After different treatments, in group B 4,000U/min infusion of UK induced the best reperfusion, the least neurological deficits and infarct volume, as well as the least mortality and lowest incidence of hemorrhage. The effect of intra-artery thrombolysis of urokinase was related to the infusion rate. Our study demonstrated an optimal infusion rate at 4,000U/min, suggesting relatively low levels of infusion are better able to improve brain reperfusion and reduce brain injury after stroke.

Download Full-text

Mature Adult Mice With Exercise-Preconditioning Show Better Recovery After Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.120.032201 ◽

2021 ◽

Vol 52 (5) ◽

pp. 1861-1865

Author(s):

Keita Kinoshita ◽

Gen Hamanaka ◽

Ryo Ohtomo ◽

Hajime Takase ◽

Kelly K. Chung ◽

...

Keyword(s):

Physical Exercise ◽

Intracerebral Hemorrhage ◽

Treadmill Exercise ◽

Neurological Deficits ◽

Multiple Time ◽

Lesion Volume ◽

Soluble Factors ◽

Mature Adult ◽

Adult Mice ◽

Exercise Preconditioning

Background and Purpose: Physical exercise offers therapeutic potentials for several central nervous system disorders, including stroke and cardiovascular diseases. However, it is still mostly unknown whether and how exercise preconditioning affects the prognosis of intracerebral hemorrhage (ICH). In this study, we examined the effects of preconditioning on ICH pathology in mature adult mice using treadmill exercise. Methods: Male C57BL/6J (25-week old) mice were subjected to 6 weeks of treadmill exercise followed by ICH induction. Outcome measurements included various neurological function tests at multiple time points and the assessment of lesion volume at 8 days after ICH induction. In addition, plasma soluble factors and phagocytotic microglial numbers in the peri-lesion area were also measured to determine the mechanisms underlying the effects of exercise preconditioning. Results: The 6-week treadmill exercise preconditioning promoted recovery from ICH-induced neurological deficits in mice. In addition, mice with exercise preconditioning showed smaller lesion volumes and increased numbers of phagocytotic microglia. Furthermore, the levels of several soluble factors, including endostatin, IGFBP (insulin-like growth factor-binding protein)-2 and -3, MMP (matrix metallopeptidase)-9, osteopontin, and pentraxin-3, were increased in the plasma samples from ICH mice with exercise preconditioning compared with ICH mice without exercise. Conclusions: These results suggest that mice with exercise preconditioning may suffer less severe injury from hemorrhagic stroke, and therefore, a habit of physical exercise may improve brain health even in middle adulthood.

Download Full-text

The Effects of Exercise Intensity on p-NR2B Expression in Cerebral Ischemic Rats

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100015341 ◽

2012 ◽

Vol 39 (5) ◽

pp. 613-618 ◽

Cited By ~ 11

Author(s):

Anjing Zhang ◽

Yulong Bai ◽

Yongshan Hu ◽

Feng Zhang ◽

Yi Wu ◽

...

Keyword(s):

Body Weight ◽

Physical Exercise ◽

Functional Recovery ◽

Exercise Intensity ◽

Treadmill Exercise ◽

Infarct Volume ◽

Brain Infarct ◽

Post Stroke ◽

Cerebral Ischemic ◽

Intensity Training

Background:The current study explored the effects of treadmill exercise intensity on functional recovery and hippocampal phospho-NR2B (p-NR2B) expression in cerebral ischemic rats, induced by permanent middle cerebral artery occlusion (MCAO) surgery.Method:Adult male Sprague-Dawley rats were randomly divided into four groups, including sham, no exercise (NE), low intensity training (LIT, v = 15 m/min), and moderate intensity training groups (MIT, v = 20 m/min). At different time points, the hippocampal expressions of p-NR2B and total NR2B were examined. In addition, neurological deficit score (NDS), body weight, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate brain infarct volume as assessments of post-stroke functional recovery. In order to investigate the effect of exercise on survival, the mortality rate was also recorded.Results:The results showed that treadmill exercise significantly decreased hippocampal expression of p-NR2B but didn't change the total NR2B, compared to the NE group on the 3rd, 7th, and 14th days following MCAO surgery. The effect on changes in p-NR2B levels, body weight, and brain infarct volume were more significant in the LIT compared to the MIT group.Discussion and Conclusion:The current findings demonstrate that physical exercise can produce neuroprotective effects, in part by down-regulating p-NR2B expression. Furthermore, the appropriate intensity of physical exercise is critical for post-stroke rehabilitation.

Download Full-text

A20-Binding Inhibitor of NF-κB 1 Ameliorates Neuroinflammation and Mediates Antineuroinflammatory Effect of Electroacupuncture in Cerebral Ischemia/Reperfusion Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6980398 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Xueling Zhou ◽

Wenhao Lu ◽

You Wang ◽

Jiani Li ◽

Yong Luo

Keyword(s):

Cerebral Ischemia ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Ischemia Reperfusion ◽

Artery Occlusion ◽

Neurological Deficits ◽

Sprague Dawley ◽

Cerebral Ischemia Reperfusion ◽

Neuroprotective Strategy

A20-binding inhibitor of NF-κB 1 (ABIN1) is an inhibitor of NF-κB and exerts anti-inflammatory effect. Electroacupuncture (EA) is considered as a neuroprotective strategy by inhibiting neuroinflammatory damage after cerebral ischemia. This study was performed to explore the role of ABIN1 and investigate whether the ABIN1 is involved in the mechanism of EA in cerebral ischemia/reperfusion (I/R) rats. Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and received EA after reperfusion once a day. Lentivirus-mediated ABIN1 gene knockdown was used to detect the role of ABIN1 in neuroinflammation after I/R. ABIN1 expression, proinflammatory cytokine levels, microglial activation, neurological function, infarct volumes, and NF-κB activation were assessed. ABIN1 expression was elevated in the peri-infarct cortex and was further upregulated by EA. ABIN1 knockdown increased the levels of proinflammatory cytokines and activation of microglia, worsened neurological deficits, and enlarged the infarct volume. Moreover, ABIN1 was blocked to partially reverse the neuroprotective effect of EA, and this treatment weakened the ability of EA to suppress NF-κB activity. Based on these findings, ABIN1 is a potential suppressor of neuroinflammation and ABIN1 mediates the antineuroinflammatory effect of EA in cerebral I/R rats.

Download Full-text

Intracisternal Basic Fibroblast Growth Factor (bFGF) Enhances Behavioral Recovery following Focal Cerebral Infarction in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199607000-00003 ◽

1996 ◽

Vol 16 (4) ◽

pp. 542-547 ◽

Cited By ~ 124

Author(s):

Takakazu Kawamata ◽

Nancy E. Alexis ◽

W. Dalton Dietrich ◽

Seth P. Finklestein

Keyword(s):

Growth Factor ◽

Infarct Size ◽

Fibroblast Growth Factor ◽

Basic Fibroblast Growth Factor ◽

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Neurological Deficits ◽

Fibroblast Growth ◽

Sprague Dawley ◽

Behavioral Recovery

Basic fibroblast growth factor (bFGF) is a potent neurotrophic agent that promotes neuronal survival and outgrowth. Previous studies have shown that bFGF, administered intraventricularly or intravenously before or within hours after ischemia, reduces infarct size and neurological deficits in models of focal cerebral ischemia in rats. In the current study, we tested the hypothesis that bFGF, administered at later time points after ischemia, might improve behavioral recovery without affecting infarct size. Mature Sprague–Dawley rats received bFGF (1 μg/injection) or vehicle by biweekly intracisternal injection for 4 weeks, starting at 1 day following permanent proximal middle cerebral artery (MCA) occlusion. Animals were examined every other day using four different behavioral tests to assess sensorimotor and reflex function. At 4 weeks after ischemia, there was no difference in infarct volume between bFGF- and vehicle-treated animals. There was, however, an enhancement in the rate and degree of behavioral recovery among bFGF-treated animals, as measured by all four tests. There were no apparent side effects of bFGF treatment, except that bFGF-treated animals tended to recover body weight more slowly than did vehicle-treated animals following stroke. The mechanisms of enhancement of behavioral recovery by bFGF require further study, but may include protection against retrograde neuronal death and/or stimulation of neuronal sprouting.

Download Full-text

Inhibition of glycogen synthase kinase-3β is involved in cardioprotection by α7nAChR agonist and limb remote ischemic postconditionings

Bioscience Reports ◽

10.1042/bsr20181315 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 4

Author(s):

Hui-Xian Li ◽

Xin-Long Cui ◽

Fu-Shan Xue ◽

Gui-Zhen Yang ◽

Ya-Yang Liu ◽

...

Keyword(s):

Glycogen Synthase ◽

Ischemic Postconditioning ◽

Glycogen Synthase Kinase ◽

Glycogen Synthase Kinase 3Β ◽

Sprague Dawley ◽

High Mobility Group Protein ◽

Remote Ischemic Postconditioning ◽

Tnf Α ◽

Creatine Kinase Mb ◽

Gsk 3Β

The present study was designed to determine whether glycogen synthase kinase-3β (GSK-3β) was involved in the cardioprotection by α7 nicotinic acetylcholine receptor (α7nAChR) agonist and limb remote ischemic postconditionings. Forty male Sprague-Dawley rats were randomly divided equally into control (C), α7nAChR agonist postconditioning (P), limb remote ischemic postconditioning (L), combined α7nAChR agonist and limb remote ischemic postconditioning (P+L) groups. At the end of experiment, serum cTnI, creatine kinase-MB (CK-MB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high mobility group protein (HMGB1) and interleukin-10 (IL-10) levels were measured; infarct size (IS), myocardial expressions of GSK-3β, p-GSK-3β (Ser9), nuclear factor-κB (NF-κB) and p-NF-κB (Ser536) in the ischemic area were assessed. The results showed that compared with group C, IS, serum cTnI and CK-MB levels obviously decreased in groups P, L and P+L. Compared with groups P and L, IS, serum cTnI and CK-MB levels significantly decreased in group P+L. Compared with group C, serum TNF-α, IL-6 and HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) evidently decreased, and myocardial expression of p-GSK-3β (Ser9) obviously increased in groups P, L and P+L. Compared with group P, serum TNF-α, IL-6 and HMGB1 levels and myocardial expression of p-NF-κBp65 (Ser536) significantly increased, and myocardial expression of p-GSK-3β (Ser9) evidently decreased in group L. Compared with group L, serum TNF-α, IL-6, HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) significantly decreased, and myocardial expression of p-GSK-3β (Ser9) obviously increased in group P+L. In conclusion, our findings indicate that inhibition of GSK-3β to decrease NF-κB transcription is one of cardioprotective mechanisms of α7nAChR agonist and limb remote ischemic postconditionings by anti-inflammation, but improved cardioprotection by combined two interventions is not completely attributable to an enhanced anti-inflammatory mechanism.

Download Full-text

Remote Limb Ischemic Postconditioning Ameliorated Microglia-Mediated Inflammation Against Cerebral Ischemia/Reperfusion through Modulating Microglial Activation and Polarization via TLR4 Pathway

10.21203/rs.3.rs-1057666/v1 ◽

2021 ◽

Author(s):

Dan Huang ◽

Leyuan Zhang ◽

Jiaju Zhong ◽

Youli Zou ◽

Guanghong Yuan ◽

...

Keyword(s):

Cerebral Ischemia ◽

Inflammatory Response ◽

Infarct Size ◽

Microglial Activation ◽

Ischemia Reperfusion ◽

Ischemic Postconditioning ◽

Neurological Deficits ◽

Sprague Dawley ◽

Nissl Staining ◽

Cerebral Ischemia Reperfusion

Abstract Accumulating researches have indicated that remote limb ischemic postconditioning (RIPC) mediates neuroprotection by inhibition inflammatory response against cerebral ischemia/reperfusion (I/R), which is proved to correlated with microglial activation and polarization. However, the underlying mechanism remains unclear. In this study, middle cerebral artery occlusion /reperfusion model in Sprague-Dawley rats were conducted and treated with vehicle or RIPC immediately after reperfusion. Infarct size, and neurological scores were performed to asses stroke outcomes for 7 days. Brain damage and neuronal survival were detected using HE and Nissl staining. ELISA, western blotting and immunohistochemistry staining were utilized to evaluate inflammatory response, neuronal apoptosis, and microglial activation and polarization to M1- or M2-subtypes respectively. Results showed that RIPC significantly attenuated infarct size at 3d and alleviated the neurological deficits of rats at 3d and 7d post-ischemia. Furthermore, RIPC decreased expression of inflammatory cytokines IL-β, TNF-α and neuronal loss, and increased expression of cytokines IL-10 and Bcl-2. In addition, RIPC suppressed microglial activation and promoted microglial polarization to M2 type along with downregulation of TLR4 expression. These results suggested that RIPC was neuroprotective against ischemic stroke by modulating the activation of microglia/macrophages and encouraging polarization to M2 phenotype possibly through TLR4 signaling pathway.

Download Full-text