scholarly journals Mitochondrial Fusion and Fission in Neuronal Death Induced by Cerebral Ischemia-Reperfusion and Its Clinical Application: A Mini-Review

2020 ◽  
Vol 26 ◽  
Author(s):  
Yike Chen ◽  
Songxue Guo ◽  
Yajuan Tang ◽  
Chaohui Mou ◽  
Xinben Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Clinical Application ◽  
Neuronal Death ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fusion ◽  
Cerebral Ischemia Reperfusion

Abstract T P84: Neuroprotective Effect of Probenecid in a Rat Model of Transient Global Cerebral Ischemia-Reperfusion

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rui-li Wei ◽  
Yan Xu ◽  
Jing-ye Wang ◽  
Ben-yan Luo
Keyword(s):  
Cerebral Ischemia ◽  
Protective Effect ◽  
Neuronal Death ◽  
Ischemia Reperfusion ◽  
Cerebral Injury ◽  
Therapeutic Drug ◽  
Ca1 Region ◽  
Cerebral Ischemia Reperfusion ◽  
Hippocampal Ca1

Background and Purpose: Probenecid (PROB) has been used for decades to treat gouty arthritis with few side effects and recent studies revealed that it is also a specific inhibitor of pannexin-1 channel. Panx1 channel was activated by ischemic injury and inhibition of the panx1 channel maybe efficacious in stroke treatment. However, the role of PROB in cerebral ischemia /reperfusion (I/R) injury remains unclear. The aim of this study was to investigate the role of PROB in the transient global cerebral I/R injury in rats and its protective mechanisms. Methods: Twenty minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO) method in rats. PROB was given in the different dose, time and administration routes to verify its neuroprotective effects. Neuronal death in the hippocampal CA1 region was observed using H & E staining 7 days after ischemia. Molecular mechanisms of activation of calpain-cathepsin pathway and inflammatory cells by I/R injury were also investigated. Results: Treatment with PROB (0.1, 1 and 10 mg/kg ) 10 min before ischemia protected against I/R-induced hippocampal CA1 neuronal death significantly, and 1 mg/kg has best protective effect. Post-insult treatment 2h after reperfusion also protected against neuronal death and prolonged use for continuous 7 days could improve its protective effects compared to the single use 6h after reperfusion.Furthermore,oral administration also had protective effect. Cathepsin B expression was inceased significantly in CA-1 region after ischemia and PROB treatment could inhibit its expression. Expression of both calpain-1 and hsp70 at 1d ,2d and 3d after reperfusion were upregulated, whereas the expression of calpain-1 was inhibited and hsp70 was strengthened by pre-treatment with PROB. Prolonged PROB treatment suppressed the activation of microglia and astrocytes, reduced the number of microglia in CA1 region. Conclusions: Our study indicates that PROB protects against transient global cerebral I/R injury administrated before ischemia and even 6h after reperfusion by reducing calpain-1 expression , inhibiting lysosomal rupture and the activation of the glia, which suggests RPOB may be a promising therapeutic drug for clinical treatment of ischemic cerebral injury.

scholarly journals Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke

2021 ◽  
Vol 8 ◽  
Author(s):  
Jaepyo Jeon ◽  
Fan Bu ◽  
Guanghua Sun ◽  
Jin-Bin Tian ◽  
Shun-Ming Ting ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Neurodegenerative Diseases ◽  
Glutamate Receptors ◽  
Neuronal Death ◽  
Metabotropic Glutamate Receptors ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion ◽  
Trpc Channels ◽  
Cerebral Ischemia Reperfusion

The seven canonical members of transient receptor potential (TRPC) proteins form cation channels that evoke membrane depolarization and intracellular calcium concentration ([Ca2+]i) rise, which are not only important for regulating cell function but their deregulation can also lead to cell damage. Recent studies have implicated complex roles of TRPC channels in neurodegenerative diseases including ischemic stroke. Brain ischemia reduces oxygen and glucose supply to neurons, i.e., Oxygen and Glucose Deprivation (OGD), resulting in [Ca2+]i elevation, ion dyshomeostasis, and excitotoxicity, which are also common in many forms of neurodegenerative diseases. Although ionotropic glutamate receptors, e.g., N-methyl-D-aspartate receptors, are well established to play roles in excitotoxicity, the contribution of metabotropic glutamate receptors and their downstream effectors, i.e., TRPC channels, should not be neglected. Here, we summarize the current findings about contributions of TRPC channels in neurodegenerative diseases, with a focus on OGD-induced neuronal death and rodent models of cerebral ischemia/reperfusion. TRPC channels play both detrimental and protective roles to neurodegeneration depending on the TRPC subtype and specific pathological conditions involved. When illustrated the mechanisms by which TRPC channels are involved in neuronal survival or death seem differ greatly, implicating diverse and complex regulation. We provide our own data showing that TRPC1/C4/C5, especially TRPC4, may be generally detrimental in OGD and cerebral ischemia/reperfusion. We propose that although TRPC channels significantly contribute to ischemic neuronal death, detailed mechanisms and specific roles of TRPC subtypes in brain injury at different stages of ischemia/reperfusion and in different brain regions need to be carefully and systematically investigated.

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