The effect of pre- and posttreatment with diazoxide on the early phase of chronic cerebral hypoperfusion in the rat

Brain Research
Eszter FarkasFerenc Bari

Abstract

Diazoxide has been identified as a mitochondrial, ATP-dependent K(+) channel opener, and a potentially neuroprotective compound under ischemic conditions. We set out to characterize the consequences of various treatment strategies with diazoxide in a rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent, bilateral occlusion of the common carotid arteries (2VO, n = 36), sham-operated rats serving as controls (SHAM, n = 29). Diazoxide or its vehicle was administered i.p. daily (5 x 0.5 mg/kg/0.25 ml) or as a bolus injection (5 mg/kg/0.25 ml) before surgery or daily after surgery (5 x 0.5 mg/kg/0.25 ml). Spatial learning performance was assessed 1 week after 2VO in the Morris maze. Hippocampal pyramidal cell loss was assessed on cresyl violet-stained sections, while glial reactivity was labeled immunocytochemically. Daily or bolus pretreatment with diazoxide significantly improved 2VO-related learning impairment, whereas posttreatment was ineffective. The number of CA1 pyramidal neurons was reduced by 2VO, which was prevented by repeated or bolus pretreatment with diazoxide. Astrocyte proliferation and microglial activation were enhanced by posttreatment with diazoxide in the hippocampus CA1 ...Continue Reading

References

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Citations

Jul 30, 2010·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Li ZhangYang Wang
Apr 14, 2010·International Journal of Molecular Sciences·Krisztina SzabadfiTamas Atlasz
Jul 17, 2012·Neurología : publicación oficial de la Sociedad Española de Neurología·Y Castaño GuerreroS Piedras Carpio
Feb 21, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Kristopher D LangdonDale Corbett
Mar 31, 2007·Journal of Neurochemistry·Tamás GáspárDavid W Busija
Dec 17, 2014·Frontiers in Aging Neuroscience·Daniele LanaMaria Grazia Giovannini
May 29, 2016·Cellular and Molecular Neurobiology·Jin-A Park, Choong-Hyun Lee
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Jun 1, 2008·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Seul-Ki KimSeong Yun Kim
Apr 3, 2007·Neurochemical Research·Veysel Haktan OzacmakAysenur Akyildiz-Igdem
Apr 5, 2020·International Journal of Molecular Sciences·Amelia Nur VidyantiChaur-Jong Hu
Apr 2, 2021·Neurologia Medico-chirurgica·Tsukasa HiranoNobuhiro Mikuni

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