scholarly journals Genome-Wide Transcription Analysis of Electroacupuncture Precondition-Induced Ischemic Tolerance on SD Rat With Ischemia–Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuping Fu ◽  
Meiling Yu ◽  
Houxi Xu ◽  
Qing Liu ◽  
Xiaoxiao Li ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Ischemic Tolerance ◽  
Neurological Deficits ◽  
Transcription Analysis ◽  
Ischemic Brain ◽  
Rehabilitative Treatment ◽  
Genome Wide ◽  
Infarction Volume

Acupuncture promotes the recovery of neurological function by the overall improvement of ischemic brain injury. It is not only regarded as a rehabilitative treatment but also a pretreatment method for stroke. However, its mechanism has not been fully elucidated. In this study, rats were treated with electroacupuncture (EA) at Baihui (GV20) for 30 min/day for 6 days, ahead of conducting cerebral ischemia–reperfusion (I/R) injury. Infarction volume, Evans blue leakage, and neurological deficits were evaluated at 24 h after I/R injury. Then, the ipsilateral ischemic brain was isolated for RNA sequencing (RNA-Seq) to identify molecular consequences. The results showed that EA pretreatment decreased blood–brain barrier (BBB) permeability, reduced brain infarction volume, and improved neurological outcomes. EA pretreatment could upregulate expression of antivirus and immunity activity-associated genes (such as Ifit1, Ifit3, Irf7, and Oasla) and downregulate expression of matrix disruption-associated genes (Col24a1, Col11a1, Col27a1, etc.) in healthy rats. In addition, it could partially reverse or ameliorate genome-wide transcription changes of the ipsilateral ischemic brain. For the first time, this study provides insight into genomic network modulation of a healthy rat with EA treatment and a EA-preconditioned rat under subsequent I/R injury, which is helpful in explaining acupuncture precondition-induced ischemic tolerance of stroke. It also provides new strategies and targets for the prevention of ischemic stroke.

scholarly journals FTY720 Protects Against Ischemia–Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model

2020 ◽  
Vol 11 (5) ◽  
pp. 1103-1116 ◽  
Author(s):  
Zifeng Wang ◽  
Kei Higashikawa ◽  
Hironobu Yasui ◽  
Yuji Kuge ◽  
Yusuke Ohno ◽  
...  
Keyword(s):  
Cell Death ◽  
Tight Junction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Neurological Deficits ◽  
Experimental Stroke ◽  
Vehicle Group ◽  
Tight Junction Proteins ◽  
Junction Proteins

Abstract Injury due to brain ischemia followed by reperfusion (I/R) may be an important therapeutic target in the era of thrombectomy. FTY720, a widely known sphingosine-1-phosphate receptor agonist, exerts various neuroprotective effects. The aim of this study was to examine the protective effect of FTY720 with respect to I/R injury, especially focusing on blood–brain barrier (BBB) protection and anti-inflammatory effects. Male rats were subjected to transient ischemia and administered vehicle or 0.5 or 1.5 mg/kg of FTY720 immediately before reperfusion. Positron emission tomography (PET) with [18F]DPA-714 was performed 2 and 9 days after the insult to serially monitor neuroinflammation. Bovine and rat brain microvascular endothelial cells (MVECs) were also subjected to oxygen-glucose deprivation (OGD) and reperfusion, and administered FTY720, phosphorylated-FTY720 (FTY720-P), or their inhibitor. FTY720 dose-dependently reduced cell death, the infarct size, cell death including apoptosis, and inflammation. It also ameliorated BBB disruption and neurological deficits compared to in the vehicle group. PET indicated that FTY720 significantly inhibited the worsening of inflammation in later stages. FTY720-P significantly prevented the intracellular redistribution of tight junction proteins but did not increase their mRNA expression. These results suggest that FTY720 can ameliorate I/R injury by protecting the BBB and regulating neuroinflammation.

Nomilin protects against cerebral ischemia–reperfusion induced neurological deficits and blood–brain barrier disruption via the Nrf2 pathway

2019 ◽  
Vol 10 (9) ◽  
pp. 5323-5332 ◽  
Author(s):  
Yu-Sheng Shi ◽  
Yan Zhang ◽  
Bin Liu ◽  
Chun-Bin Li ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Nrf2 Pathway ◽  
Blood Brain Barrier Disruption ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Brain Barrier Disruption

Oxidative stress is considered to play an important role in the cerebral ischemia–reperfusion injury.

scholarly journals HMBG1 Mediates Ischemia—Reperfusion Injury by TRIF-Adaptor Independent Toll-Like Receptor 4 Signaling

2010 ◽  
Vol 31 (2) ◽  
pp. 593-605 ◽  
Author(s):  
Qing-Wu Yang ◽  
Feng-Lin Lu ◽  
Yu Zhou ◽  
Lin Wang ◽  
Qi Zhong ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Brain Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Hmgb1 Level ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

High-mobility group protein box-1 (HMGB1) has recently been recognized as a novel candidate in a specific upstream pathway promoting inflammation after brain ischemia. However, its downstream pathway and underlying mechanism have yet to be elucidated. The HMGB1 level in the acute cerebral infarct (ACI) group was significantly increased compared with that of control group, and correlated with the severity of neurologic impairment of ACI patients. Further, recombinant human HMGB1 (rhHMGB1) had no effect on microglia derived from mice lacking the Toll-like receptor 4 (TLR4−/–). Intracerebroventricular injection of rhHMGB1 in TLR4+/+ mice cause significantly more injury after cerebral ischemia–reperfusion than control group. But, TLR4−/– mice administered with rhHMGB1 showed moderate impairment after ischemia–reperfusion than TLR4+/+ mice. To determine the potential downstream signaling of HMGB1/TLR4 in cerebral ischemic injury, we used the ischemic–reperfusion model with Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β knockout mice (TRIF−/–) and evaluated the activity and expression of TRIF pathway-related kinases. The results suggest that the TRIF pathway is not likely to be involved in TLR4-mediated ischemia brain injury. Finally, we found that TLR4 expressed by immigrant macrophages was involved in the development of ischemic brain damage. These results suggest that HMBG1 mediates ischemia–reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling. The TLR4 expressed by immigrant macrophages may be involved in the development of ischemic brain damage.

Neuroprotective Effects of Bone Marrow Mononuclear Cells Therapy in a Rat Model of Ischemia Stroke

2020 ◽  
Vol 10 (3) ◽  
pp. 346-351
Author(s):  
Jianfeng Liu ◽  
Yamei Hu ◽  
Gang Li ◽  
Qianlin Zhang ◽  
Jiewen Zhang
Keyword(s):  
Bone Marrow ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Bone Marrow Mononuclear Cells ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Rat Models

Objective: Bone marrow mononuclear cells (BMMCs) are considered a potential approach to promote the recovery of stroke-induced neurological deficit. However, the exact mechanism of BMMCs in nerve function recovery is still unclear. Methods: Adult Sprague-Dawley (SD) rat models of cerebral ischemia-reperfusion injury was established by using thread method. BMMCs were transplanted into rat models. Neurological deficits were evaluated by Longa score scale. Immunohistochemistry assay were employed to examine the expression of GFAP and Nogo-A around the ischemic foci in the right frontal lobe. Caspase-3 activity was examined by Western Blot. Results: Rats in BMMCs group had lessened neurological deficits and cleaved Caspase-3 expression on day 21 after reper-fusion, as well as higher expression of GFAP [(37.62±2.45) vs. (27.62±1.69) and (38.00±1.85) vs. (27.25±1.83), P < 0.05] and lower expression of Nogo-A [(28.88±2.64) vs. (32.50±1.60) and (23.87±2.36) vs. (32.00±1.85), P < 0.05] on day 14 and 21 after reperfusion. Meanwhile, the expression of Nogo-A on day 21 was lower than that on day 14 after reperfusion [(23.87±2.36) vs. (28.88±2.64), P < 0.05] in BMMCs group. Conclusion: These findings suggested that BMMCs treatment could improve the functional recovery of neurological deficits in rats with MCAO, which was probably related to enhanced expression of GFAP and reduced Nogo-A expression and Caspase-3 activity in the ischemic brain tissues.

scholarly journals Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury

2019 ◽  
Author(s):  
Mengya Jiao ◽  
Xiangyong Li ◽  
Xiaodi Wang ◽  
Liying Chen ◽  
Baohong Yuan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Brain Injury ◽  
Neurotrophic Factor ◽  
Inflammatory Responses ◽  
Neuroprotective Effect ◽  
Brain Infarction ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
Ischemic Brain

Abstract Background: Interleukin-33 (IL-33) is a well-recognized pleiotropic cytokine which plays crucial roles in immune regulation and inflammatory responses. Recent studies suggest that IL-33 and its receptor ST2 are involved in the pathogenesis of neurological diseases. Here, we explore the effect of IL-33/ST2 signaling in neonatal hypoxic-ischemic (HI) brain injury and elucidate the underlying mechanisms of action. Methods: The brain HI model was established in neonatal C57BL/6 mice by left common carotid artery occlusion with 90 min hypoxia, and treated with IL-33 at a dose of 0.2 μg/day i.p. for three days. TTC staining and neurobehavioral observation were used to evaluate the HI brain injury. Immunofluorescence and flow cytometry were applied to determine the expression of IL-33 and its receptor ST2 on brain CNS cells, cell proliferation and apoptosis. OGD experiment was used to assay the viability of astrocytes and neurons. RT-qPCR was used to measure the expression of neurotrophic factor-associated genes. Results: The expression level of IL-33 was markedly enhanced in astrocytes 24 h after cerebral HI in neonatal mice. Exogenous delivery of IL-33 significantly alleviated brain injury 7 d after HI, whereas ST2 deficiency exacerbated brain infarction and neurological deficits post HI. Flow cytometry analyses demonstrated high levels of ST2 expression on astrocytes, and the expression of ST2 was further elevated after HI. Intriguingly, IL-33 treatment apparently improved astrocyte response and attenuated HI-induced astrocyte apoptosis through ST2 signaling pathways. Further in vitro studies revealed that IL-33-activated astrocytes released a series of neurotrophic factors, which are critical for raising neuronal survival against oxygen glucose deprivation. Conclusions: The activation of IL-33/ST2 signaling in the ischemic brain improves astrocyte response, which in turn affords protection to ischemic neurons in a glial-derived neurotrophic factor-dependent manner.

P6299Dietary nitrate restores cardiac ischemic tolerance in type 2 diabetic mice and protects against ischemia-reperfusion injury via soluble guanylate cyclase in red blood cells

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J N Yang ◽  
T Jiao ◽  
Y Tratsiakovich ◽  
A Mahdi ◽  
Z Zhou ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Blood Cells ◽  
Soluble Guanylate Cyclase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Tolerance ◽  
Dietary Nitrate ◽  
Nitrate Supplementation ◽  
Type 2 Diabetic

Abstract Background Inorganic nitrate has been shown to exert beneficial cardiovascular effects, which are thought to be mediated via sequential reduction of nitrate to nitrite and nitric oxide (NO). We have previously reported that hearts from type 2 diabetic db/db mice have impaired cardiac ischemic tolerance and that this effect involves reduced export of NO-like bioactivity from red blood cells (RBCs). It remains unknown whether nitrate supplementation may affect cardiac ischemic tolerance in diabetes through interference with RBC function. Purpose To test the hypothesis that dietary nitrate supplementation improves cardiac ischemic tolerance of hearts via an effect mediated through RBCs in type 2 diabetes. Methods Type 2 diabetic (db/db) and wild type (WT) mice on nitrate-free chow were treated with vehicle or nitrate (1 mM) in the drinking water for 4 weeks. Hearts were isolated and perfused using the Langendorff technique. After 30 min stabilization, the hearts were subjected to 40 min global ischemia followed by 60 min reperfusion. In protocol 1, isolated hearts from db/db and WT mice given vehicle or nitrate were perfused with buffer. In protocol 2, only hearts from untreated WT mice were used. Washed RBCs from WT or db/db mice treated with vehicle or nitrate were administered to WT hearts at the onset of ischemia with and without the soluble guanylyl cyclase (sGC) inhibitor (1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ). In both protocols post-ischemic recovery of cardiac function was evaluated by determination of left ventricular developed pressure (LVDP). Results In Protocol 1, post-ischemic recovery of LVDP was impaired in hearts from db/db mice in comparison with hearts from WT mice (Fig. A). Dietary nitrate restored the ischemic tolerance of hearts from db/db mice but did not affect post-ischemic recovery of hearts from WT mice (Fig. A). In Protocol 2, administration of RBCs collected from vehicle-treated db/db mice significantly impaired post-ischemic recovery of hearts from WT mice (Fig. B). Notably, administration of RBCs from nitrate-treated db/db mice completely reversed the impairment of post-ischemic cardiac function induced by diabetic RBCs (Fig. B). Interestingly, post-ischemic cardiac function did not differ between hearts given RBCs from nitrate-treated db/db and WT mice (Fig. B). The protective effect of RBCs from nitrate-treated mice was abolished by pre-incubation of the RBCs with ODQ, an inhibitor of soluble guanylate cyclase (sGC) (Fig. C). By contrast, pretreatment of isolated WT hearts with ODQ failed to block the protective effect of RBCs from nitrate-treated mice (Fig C) indicating that sGC in the RBC but not in the heart is critical for nitrate-induced cardiac protection. Conclusion Dietary nitrate restores cardiac ischemic tolerance in db/db mice and protects the heart against ischemia–reperfusion injury via an RBC NO-sGC pathway.

ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1650-1653 ◽  
Author(s):  
Masayuki Fujioka ◽  
Kazuhide Hayakawa ◽  
Kenichi Mishima ◽  
Ai Kunizawa ◽  
Keiichi Irie ◽  
...  
Keyword(s):  
Brain Damage ◽  
Gene Deletion ◽  
Ischemia Reperfusion Injury ◽  
Thrombus Formation ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Platelet Glycoprotein ◽  
Wild Type ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

Abstract Reperfusion after brain ischemia causes thrombus formation and microcirculatory disturbances, which are dependent on the platelet glycoprotein Ib–von Willebrand factor (VWF) axis. Because ADAMTS13 cleaves VWF and limits platelet-dependent thrombus growth, ADAMTS13 may ameliorate ischemic brain damage in acute stroke. We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion model in Adamts13−/− and wild-type mice. After reperfusion for 0.5 hours, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13−/− mice compared with wild-type mice (P < .05), which also resulted in a larger infarct volume after 24 hours for Adamts13−/− compared with wild-type mice (P < .01). Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion. These results indicate that ADAMTS13 may be a useful therapeutic agent for stroke.

Abstract 137: The Effect Of Mitophagy During Transient Ischemic Brain In Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Qiang Li ◽  
Ting Zhang ◽  
Jixian Wang ◽  
Yongting Wang ◽  
Guo-Yuan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Atp Synthesis ◽  
Beclin 1 ◽  
Neurological Deficits ◽  
Ischemic Brain ◽  
Pre Treatment ◽  
The Impact

Background and Purpose: Mitochondria provides energy to maintain normal cell functioning. Mitophagy is one of mitochondria functions, which can clear out injured mitochondria, ensure stability of mitochondria and promote cell survival in hostile environment. However, if mitophagy occurs during cerebral ischemia is unknown. The present study explored dynamic mitophagy, the effect of promoting mitophagy, and the molecular mechanisms of mitophagy during cerebral ischemia/reperfusion. Methods: Adult male SD rats underwent 2h middle cerebral artery occlusion (MCAO) followed by 6 to 72h reperfusion. Dynamic changes of mitophagy were determined by LC3 immunostaining, Western blot analysis, and transmission electron microscope. To study the impact of mitophagy, we injected rapamycin, a mitophagy stimulator, into the left ventricle in rats underwent transient MCAO. To evaluate the effect of mitophagy, neuronal death and neurological deficits were determined. To explore the effect of mitophagy on mitochondria function, the number of mitochondria, the levels of MDA, ATP, and JC-1 were examined. To study the mechanism of mitophagy, mitochondrial Beclin-1 and p62 expression were also determined. Results: We demonstrated that autophagy was mainly detected in mitochondria in the peri-focal area of ischemic cortex after ischemia/reperfusion. Mitophagy was increased at 6h (p<0.05), peaked at 24h (p<0.05), gradually reduced at 48h (p<0.05), and returned to normal at 72h of transient MCAO. Pre-treatment with rapamycin greatly enhanced mitophagy, reduced infarct volume, and improved neurological outcomes compared to the control (p<0.05). We found that the number of mitochondria and mtDNA copy, mitochondria ATP synthesis level, and JC-1 were increased (p<0.05), and MDA was reduced in rapamycin treated rats (p<0.05). We further demonstrated that rapamycin pre-treatment enhanced mitochondrial Beclin-1and p62 in mitochondria. Conclusion: We demonstrated ischemia could induce mitophagy in brain cells. Rapamycin attenuated ischemic brain injury, which was via stimulating mitophagy that can reduce oxidative stress and improve mitochondria function. The mechanism of rapamycin promoting mitophagy was through increasing Beclin-1 and p62 expression.

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