The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia

1981 ◽  
Vol 55 (3) ◽  
pp. 205-220 ◽  
Author(s):  
L. W. Jenkins ◽  
J. T. Povlishock ◽  
W. Lewelt ◽  
J. D. Miller ◽  
D. P. Becker
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Injury ◽  
Postischemic Recirculation ◽  
Complete Cerebral Ischemia ◽  
Ischemic Neuronal Injury

scholarly journals The Role of Parl and HtrA2 in Striatal Neuronal Injury After Transient Global Cerebral Ischemia

2013 ◽  
Vol 33 (11) ◽  
pp. 1658-1665 ◽  
Author(s):  
Hideyuki Yoshioka ◽  
Masataka Katsu ◽  
Hiroyuki Sakata ◽  
Nobuya Okami ◽  
Takuma Wakai ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Small Interfering Rna ◽  
Neuronal Injury ◽  
Global Cerebral Ischemia ◽  
Inhibitor Of Apoptosis ◽  
Transient Global Cerebral Ischemia ◽  
Apoptosis Protein ◽  
Interfering Rna ◽  
Ischemic Neuronal Injury

The presenilin-associated rhomboid-like (PARL) protein and high temperature requirement factor A2 (HtrA2) are key regulators of mitochondrial integrity and play pivotal roles in apoptosis. However, their roles after cerebral ischemia have not been thoroughly elucidated. To clarify these roles, mice were subjected to transient global cerebral ischemia, and striatal neuronal injury was assessed. Western blot and coimmunoprecipitation analyses revealed that PARL and processed HtrA2 localized to mitochondria, and that PARL was bound to HtrA2 in sham animals. Expression of PARL and processed HtrA2 in mitochondria significantly decreased 6 to 72 hours after ischemia, and the binding of PARL to HtrA2 disappeared after ischemia. In contrast, expression of processed HtrA2 increased 24 hours after ischemia in the cytosol, where HtrA2 was bound to X chromosome-linked inhibitor-of-apoptosis protein (XIAP). Administration of PARL small interfering RNA inhibited HtrA2 processing and worsened ischemic neuronal injury. Our results show that downregulation of PARL after ischemia is a key step in ischemic neuronal injury, and that it decreases HtrA2 processing and increases neuronal vulnerability. In addition, processed HtrA2 released into the cytosol after ischemia contributes to neuronal injury via inhibition of XIAP.

scholarly journals The Role of SUMO-Conjugating Enzyme Ubc9 in the Neuroprotection of Isoflurane Preconditioning Against Ischemic Neuronal Injury

2014 ◽  
Vol 51 (3) ◽  
pp. 1221-1231 ◽  
Author(s):  
Li Tong ◽  
Zhixin Wu ◽  
Mingzi Ran ◽  
Yu Chen ◽  
Lujia Yang ◽  
...  
Keyword(s):  
Neuronal Injury ◽  
Ischemic Neuronal Injury ◽  
Conjugating Enzyme

scholarly journals Critical Role of Calpain I in Mitochondrial Release of Apoptosis-Inducing Factor in Ischemic Neuronal Injury

2007 ◽  
Vol 27 (35) ◽  
pp. 9278-9293 ◽  
Author(s):  
G. Cao ◽  
J. Xing ◽  
X. Xiao ◽  
A. K. F. Liou ◽  
Y. Gao ◽  
...  
Keyword(s):  
Critical Role ◽  
Neuronal Injury ◽  
Apoptosis Inducing Factor ◽  
Ischemic Neuronal Injury

scholarly journals 2-Methoxyestradiol Attenuates Autophagy Activation After Global Ischemia

2011 ◽  
Vol 38 (4) ◽  
pp. 631-638 ◽  
Author(s):  
Xiao-Yu Xin ◽  
Jing Pan ◽  
Xiao-Qiang Wang ◽  
Jian-Fang Ma ◽  
Jian-Qing Ding ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Injury ◽  
Global Ischemia ◽  
Beclin 1 ◽  
Cresyl Violet ◽  
Tunel Staining ◽  
Protective Effects ◽  
Vessel Occlusion ◽  
Western Blot Assay ◽  
Ischemic Neuronal Injury

Background:Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy.Methods:Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections.Results:The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury.Conclusions:This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.

scholarly journals Upregulation of Extracellular Vesicles-Encapsulated miR-132 Released From Mesenchymal Stem Cells Attenuates Ischemic Neuronal Injury by Inhibiting Smad2/c-jun Pathway via Acvr2b Suppression

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Feng ◽  
Lei Meng ◽  
Liming Luan ◽  
Zhihao Fang ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Neuronal Cell ◽  
Neuronal Injury ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Ischemic Neuronal Injury

Ischemic cerebrovascular disease is a significant and common public health issue worldwide. The emerging roles of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) in ischemic neuronal injury continue to be investigated. The current study aimed to investigate the role of EV-derived miR-132 from MSCs in ischemic neuronal injury. EVs were initially isolated from bone MSCs (BMSCs) and subsequently evaluated. A middle cerebral artery occlusion (MCAO) mouse model was constructed with the neurological function evaluated through a series of neurological scores, a pole test, and a foot fault test. Histopathological changes, neuron viability, and apoptosis, as well as cerebral infarction, were detected by hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The targeting relationship between microRNA (miR)-132 and Activin receptor type IIB (Acvr2b) was further confirmed based on dual-luciferase reporter gene assay results. Loss- and gain-of-function assays were conducted to elucidate the role of miR-132, EV-derived miR-132, Acvr2b, and Smad2 in oxygen-glucose deprivation (OGD)-treated neurons, and in mice models. Neuronal cell viability and apoptosis were evaluated via Cell Counting kit-8 (CCK-8) and flow cytometry. Our results indicated that Acvr2b was highly expressed, while miR-132 was poorly expressed in the MCAO mice and OGD-treated neurons. Acvr2b silencing or upregulation of miR-132 led to an elevation in neuronal activity, decreased neuronal apoptosis, reduced expression of Bax, and cleaved-caspase 3, as well as increased Bcl-2 expression. Acvr2b expression was targeted and inhibited by miR-132. EV-derived Acvr2b promoted activation of phosphorylated-Smad2 (p-Smad2)/c-jun signaling pathway, ultimately inducing neuronal injury. Our study provides evidence demonstrating that the overexpression of c-jun inhibits the protective role of MSCs-derived EV-miR-132 in neuronal injury. Upregulation of EV-derived miR-132 released from MSCs attenuates ischemic neuronal injury by inhibiting Smad2/c-jun pathways via the suppression of Acvr2b.

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