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Effect of pregabalin administration upon reperfusion in a rat model of hyperglycemic stroke: mechanistic insights associated with High-mobility group box 1

Other Titles
 고혈당 뇌졸중 유도 백서에서 재관류 시 프레가발린 투여가 미치는 영향과 High-mobility group box 1 관련 기전 
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Hyperglycemia, which reduces the efficacy of treatments and worsens clinical outcomes, is common in stroke. Ability of pregabalin to reduce neuroexcitotoxicity may provide protection against stroke, even under hyperglycemia. We investigated its protective effect against hyperglycemic stroke and its possible molecular mechanisms. Male Wistar rats administered dextrose to cause hyperglycemia, underwent middle cerebral artery occlusion for 1 h and subsequent reperfusion. Rats were treated with an intraperitoneal injection of 30 mg/kg pregabalin or an equal amount of normal saline at the onset of reperfusion (n = 16 per group). At 24 h after reperfusion, neurological deficit, infarct volume, and apoptotic cell count were assessed. Western blot analysis was performed to determine protein expression of high-mobility group box 1 (HMGB1), toll-like receptor-4 (TLR-4), phosphorylated nuclear factor-kappa B (p-NF-κB), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), phosphorylated inducible and endothelial nitric oxide synthase (p-iNOS, p-eNOS), Bcl-2, Bax, Cytochrome C, and caspase-3 in the brain. Pregabalin-treated rats showed significantly improved neurological function (31% decrease in score), reduced infarct size (by 33%), fewer apoptotic cells (by 63%), and lower expression levels of HMGB1, TLR4, p-NF-κB, IL-1β, and TNF- α, compared with control rats. Decreased p-iNOS and increased p-eNOS expressions were also observed. Expression of Bax, Cytochrome C, and cleaved caspase-3/caspase3 was significantly downregulated, while Bcl-2 expression was increased by pregabalin treatment. Pregabalin administration upon reperfusion decreased neuronal death and improved neurological function in hyperglycemic stroke rats. Cogent mechanisms would include attenuation of HMGB1/TLR-4-mediated inflammation and favorable modulation of the NOS.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 5. Others
Yonsei Authors
Song, Young(송영) ORCID logo https://orcid.org/0000-0003-4597-387X
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