Low-dose candesartan enhances molecular mediators of neuroplasticity and subsequent functional recovery after ischemic stroke in rats.

ABSTRACT: We have previously reported that angiotensin type 1 receptor (AT1R) blockade with candesartan exerts neurovascular protection after experimental cerebral ischemia. Here, we tested the hypothesis that a low, subhypotensive dose of candesartan enhances neuroplasticity and subsequent functional recovery through enhanced neurotrophic factor expression in rats subjected to ischemia reperfusion injury. Male Wistar rats (290-300 g) underwent 90 min of middle cerebral artery occlusion (MCAO) and received candesartan (0.3 mg/kg) or saline at reperfusion and then once every 24 h for 7 days. Functional deficits were assessed in a blinded manner at 1, 3, 7, and 14 days after MCAO. Animals were sacrificed 14-day post-stroke and the brains perfused for infarct size by cresyl violet. Western blot and immunohistochemistry were used to assess the expression of growth factors and synaptic proteins. Candesartan-treated animals showed a significant reduction in the infarct size [t (13)?=?-5.5, P?=?0.0001] accompanied by functional recovery in Bederson [F (1, 13)?=?7.9, P?=?0.015], beam walk [F (1, 13)?=?6.7, P?=?0.023], grip strength [F (1, 13)?=?15.2, P?=?0.0031], and rotarod performance [F (1, 14)?=?29.8, P?

SUBMITTER: Ishrat T 

PROVIDER: S-EPMC4677667 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature