Neuroprotection by diazoxide in animal models for cerebrovascular disorders

E. Farkas, F. Domoki, Ádám Institóris, Anita Annaházi, David W. Busija, F. Bari

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Diazoxide, a mitochondrial ATP-dependent K+ channel opener has been investigated as a potential anti-ischemic 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 drug's 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.

Original languageEnglish
Pages (from-to)253-263
Number of pages11
JournalVascular Disease Prevention
Volume3
Issue number3
DOIs
Publication statusPublished - 2006

Fingerprint

Diazoxide
Cerebrovascular Disorders
Animal Models
Neuroprotective Agents
Mitochondria
Brain
Cell Culture Techniques
Mitochondrial Size
Neuroprotection
Common Carotid Artery
Middle Cerebral Artery
Microglia
Cytochromes
Reperfusion Injury
Carotid Arteries
Pharmaceutical Preparations
Protein Kinase C
Rodentia
Reactive Oxygen Species
Cell Survival

Keywords

  • Brain
  • Cerebral hypoperfusion
  • Diazoxide
  • Ischemia
  • K-channel
  • Mitochondria
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Epidemiology

Cite this

Neuroprotection by diazoxide in animal models for cerebrovascular disorders. / Farkas, E.; Domoki, F.; Institóris, Ádám; Annaházi, Anita; Busija, David W.; Bari, F.

In: Vascular Disease Prevention, Vol. 3, No. 3, 2006, p. 253-263.

Research output: Contribution to journalArticle

Farkas, E. ; Domoki, F. ; Institóris, Ádám ; Annaházi, Anita ; Busija, David W. ; Bari, F. / Neuroprotection by diazoxide in animal models for cerebrovascular disorders. In: Vascular Disease Prevention. 2006 ; Vol. 3, No. 3. pp. 253-263.
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