Rat Model of Global Cerebral Ischemia: The Two-Vessel Occlusion (2VO) Model of Forebrain Ischemia

2019 ◽  
pp. 107-117
Author(s):  
Ami P. Raval ◽  
Chunli Liu ◽  
Bingren R. Hu
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Global Cerebral Ischemia ◽  
Forebrain Ischemia ◽  
Vessel Occlusion

scholarly journals Inhibition of MLKL-dependent necroptosis via downregulating interleukin-1R1 contributes to neuroprotection of hypoxic preconditioning in transient global cerebral ischemic rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lixuan Zhan ◽  
Xiaomei Lu ◽  
Wensheng Xu ◽  
Weiwen Sun ◽  
En Xu
Keyword(s):  
Plasma Membrane ◽  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Interleukin 1 ◽  
Hypoxic Preconditioning ◽  
Global Cerebral Ischemia ◽  
Free Calcium ◽  
Membrane Translocation ◽  
Vessel Occlusion ◽  
Transient Global Cerebral Ischemia

Abstract Background Our previous study indicated that hypoxic preconditioning reduced receptor interacting protein (RIP) 3-mediated necroptotic neuronal death in hippocampal CA1 of adult rats after transient global cerebral ischemia (tGCI). Although mixed lineage kinase domain-like (MLKL) has emerged as a crucial molecule for necroptosis induction downstream of RIP3, how MLKL executes necroptosis is not yet well understood. In this study, we aim to elucidate the molecular mechanism underlying hypoxic preconditioning that inactivates MLKL-dependent neuronal necroptosis after tGCI. Methods Transient global cerebral ischemia was induced by the four-vessel occlusion method. Twenty-four hours before ischemia, rats were exposed to systemic hypoxia with 8% O2 for 30 min. Western blotting was used to detect the expression of MLKL and interleukin-1 type 1 receptor (IL-1R1) in CA1. Immunoprecipitation was used to assess the interactions among IL-1R1, RIP3, and phosphorylated MLKL (p-MLKL). The concentration of intracellular free calcium ion (Ca2+) was measured using Fluo-4 AM. Silencing and overexpression studies were used to study the role of p-MLKL in tGCI-induced neuronal death. Results Hypoxic preconditioning decreased the phosphorylation of MLKL both in neurons and microglia of CA1 after tGCI. The knockdown of MLKL with siRNA decreased the expression of p-MLKL and exerted neuroprotective effects after tGCI, whereas treatment with lentiviral delivery of MLKL showed opposite results. Mechanistically, hypoxic preconditioning or MLKL siRNA attenuated the RIP3-p-MLKL interaction, reduced the plasma membrane translocation of p-MLKL, and blocked Ca2+ influx after tGCI. Furthermore, hypoxic preconditioning downregulated the expression of IL-1R1 in CA1 after tGCI. Additionally, neutralizing IL-1R1 with its antagonist disrupted the interaction between IL-1R1 and the necrosome, attenuated the expression and the plasma membrane translocation of p-MLKL, thus alleviating neuronal death after tGCI. Conclusions These data support that the inhibition of MLKL-dependent neuronal necroptosis through downregulating IL-1R1 contributes to neuroprotection of hypoxic preconditioning against tGCI.

A modified four vessel occlusion model of global cerebral ischemia in rats

2021 ◽  
Vol 352 ◽  
pp. 109090
Author(s):  
Wei Sun ◽  
Yeting Chen ◽  
Yongjie Zhang ◽  
Yue Geng ◽  
Xiaohang Tang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Vessel Occlusion ◽  
Occlusion Model

scholarly journals A Model of Global Cerebral Ischemia in C57 BL/6 Mice

2004 ◽  
Vol 24 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Ichiro Yonekura ◽  
Nobutaka Kawahara ◽  
Hirofumi Nakatomi ◽  
Kazuhide Furuya ◽  
Takaaki Kirino
Keyword(s):  
Cerebral Ischemia ◽  
Genetic Background ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Genetically Engineered ◽  
Global Cerebral Ischemia ◽  
Vessel Occlusion ◽  
Bilateral Carotid ◽  
The Mean

A reproducible model of global cerebral ischemia in mice is essential for elucidating the molecular mechanism of ischemic neuronal injury. Such a model is particularly important in the mouse because many genetically engineered mutant animals are available. In C57BL/6 and SV129/EMS mice, we evaluated a three-vessel occlusion model. Occlusion of the basilar artery with a miniature clip was followed by bilateral carotid occlusion. The mean cortical cerebral blood flow was reduced to less than 10% of the preischemic value, and the mean anoxic depolarization was attained within 1 minute. In C57BL/6 mice, there was CA1 hippocampal neuronal degeneration 4 days after ischemia. Neuronal damage depended upon ischemic duration: the surviving neuronal count was 78.5 ± 8.5% after 8-minute ischemia and 8.4 ± 12.7% after 14-minute ischemia. In SV129/EMS mice, similar neuronal degeneration was not observed after 14-minute ischemia. The global ischemia model in C57BL/6 mice showed high reproducibility and consistent neuronal injury in the CA1 sector, indicating that comparison of ischemic outcome between wild-type and mutant mice could provide meaningful data using the C57BL/6 genetic background. Strain differences in this study highlight the need for consideration of genetic background when evaluating ischemia experiments in mice.

scholarly journals Cyclooxygenase-2 Mediates Hyperbaric Oxygen Preconditioning in the Rat Model of Transient Global Cerebral Ischemia

Stroke ◽  
2011 ◽  
Vol 42 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Oumei Cheng ◽  
Robert P. Ostrowski ◽  
Bihua Wu ◽  
Wenwu Liu ◽  
Chunhua Chen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Hyperbaric Oxygen ◽  
Rat Model ◽  
Cyclooxygenase 2 ◽  
Global Cerebral Ischemia ◽  
Transient Global Cerebral Ischemia ◽  
Hyperbaric Oxygen Preconditioning

Post‐ischemic salubrinal administration reduces necroptosis in a rat model of global cerebral ischemia

2019 ◽  
Vol 151 (6) ◽  
pp. 777-794 ◽  
Author(s):  
Enrique Font‐Belmonte ◽  
Irene F. Ugidos ◽  
María Santos‐Galdiano ◽  
Paloma González‐Rodríguez ◽  
Berta Anuncibay‐Soto ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Global Cerebral Ischemia

Neurovascular Coupling Varies with Level of Global Cerebral Ischemia in a Rat Model

2012 ◽  
Author(s):  
Wesley B Baker ◽  
Teruyuki Hiraki ◽  
Zhenghui Sun ◽  
Mary Putt ◽  
Martin Reivich ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Neurovascular Coupling ◽  
Global Cerebral Ischemia

scholarly journals In vivo Binding of [3H]Nimodipine in Rat Brain after Transient Forebrain Ischemia

1994 ◽  
Vol 14 (3) ◽  
pp. 397-405 ◽  
Author(s):  
Shunya Takizawa ◽  
Matthew J. Hogan ◽  
Alastair M. Buchan ◽  
Antoine M. Hakim
Keyword(s):  
Cerebral Ischemia ◽  
Brain Structures ◽  
Brain Regions ◽  
Global Cerebral Ischemia ◽  
Therapeutic Window ◽  
Forebrain Ischemia ◽  
In Vivo Binding ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region

We report the regional variation in relative in vivo binding of the l-type voltage sensitive calcium channel (VSCC) antagonist [3H]nimodipine to brain following transient forebrain ischemia in the rat. At 30-min of reperfusion after 20 min of forebrain ischemia, [3H]nimodipine binding was significantly increased in striatum, CA3 and CA4, and dentate relative to binding in sham-operated rats, suggesting that VSCCs were responding to ischemic depolarization. Two h following ischemia, binding in all brain structures returned to normal levels indicating repolarization of cell membranes. At 24 h of recirculation, increased [3H]nimodipine binding was again observed in striatum and dentate. Binding remained elevated in the striatum and dentate, and increased binding became evident in the CA1 region of the hippocampus after 48 h of reperfusion. With the exception of the dentate gyrus, the second rise in [3H]nimodipine binding anticipated or coincided with the observed regional ischemic cell changes. These observations in global cerebral ischemia support previous work indicating that in vivo binding of [3H]nimodipine to the l-type VSCC may be an early and sensitive indicator of impending ischemic injury. Such measurements may be of use in identifying vulnerable brain regions and defining a therapeutic window of opportunity in models of cerebral ischemia.

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