Post-treatment with selective beta1 adrenoceptor antagonists provides neuroprotection against transient focal ischemia in rats

Abstract

We have reported the neuroprotective effects of pre-treatment with β-adrenoceptor antagonists on the cerebral infarction at 1 and 7 days after focal ischemia in rats. However, the protective effect of post-treatment with β-adrenoceptor antagonists has not been investigated yet. This study was conducted to evaluate the post-treatment effects of selective β 1-adrenoceptor antagonists in the rat focal cerebral ischemia. Halothane anesthetized, normothermic adult male Sprague–Dawley rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received intravenous infusion of saline 0.5 mL/h, esmolol 200 μg/kg/min, or landiolol 50 μg/kg/min ( n = 8 in each group). Infusion was initiated 30 min after MCAO and continued for 24 h. Rats were allowed to survive for 7 days, and the neurological deficit score was evaluated at 1, 4 and 7 days after reperfusion. The brains were removed and stained with triphenyltetrazolium chloride at 7 days after reperfusion. Neurological deficit scores were lower in the rats treated with esmolol or landiolol, compared with saline-treated rats at 1 day as well as 4 and 7 days. The infarct volumes of cortical and striatum were less in the rats receiving β-adrenoceptor antagonists than in saline-treated rats ( P < 0.05). The current study indicates that administration of selective β1-adrenoceptor antagonists after the onset of ischemia also improved neurological and histological outcomes following transient focal cerebral ischemia in rats.