Neuroprotection by Diazoxide in Animal Models for Cerebrovascular Disorders

Author(s): Eszter Farkas, Ferenc Domoki, Adam Institoris, Anita Annahazi, David W. Busija, Ferenc Bari.

Journal Name: Vascular Disease Prevention

Volume 3 , Issue 3 , 2006

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Abstract:

Diazoxide, a mitochondrial ATP-dependent K+ channel opener has been investigated as a potential antiischemic agent in the brain. The neuroprotective effect of diazoxide has emerged from in vitro experiments employing brain slices and neuronal cell cultures. The intracellular mechanisms that are responsible for the neuroprotective properties of diazoxide have also been identified in cell cultures and isolated mitochondria. Thus, diazoxide has been shown to depolarize mitochondria, preserve mitochondrial matrix volume, block cytochrome C release and Bax translocation, activate protein kinase C and facilitate the production of reactive oxygen species, which lead to enhanced cell viability and preserve electrophysiological properties of neurons after oxygen and glucose deprivation. Recently, diazoxide has been administered to experimental animals to examine the drugs effect on the ischemic brain. Various animal models of ischemic cerebrovascular disorders such as ischemia/reperfusion injury, stroke and chronic cerebral hypoperfusion were used to evaluate the neuroprotective properties of diazoxide in vivo. The results of numerous studies demonstrate that diazoxide limits infarct size after middle cerebral artery or unilateral carotid artery occlusion in rodents, preserves cerebrovascular function in newborn piglets, and reduces the activation of microglia after permanent, bilateral common carotid artery occlusion in rats. This review provides a comprehensive summary of the experimental data on the neuroprotective effects of diazoxide in animal models. This overview may facilitate drug development in this field.

Keywords: Brain, cerebral hypoperfusion, diazoxide, ischemia, K+-channel, mitochondria, stroke

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2006
Page: [253 - 263]
Pages: 11
DOI: 10.2174/1567270010603030253
Price: $58