??-Adrenoreceptor Antagonists Attenuate Brain Injury After Transient Focal Ischemia in Rats

Abstract

β-adrenoreceptor antagonists experimentally reduce cardiac and renal injury after ischemia and are also clinically useful for myocardial infarction and severe burns. In addition, β-adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. We conducted the present study to compare the neuroprotective effects of several β-adrenoreceptor antagonists in rat transient focal cerebral ischemia. Halothane-anesthetized normothermic adult male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received an IV infusion of saline 0.5 mL/h, propranolol 100 μg · kg⁻¹ · min⁻¹, carvedilol 4 μg · kg⁻¹ · min⁻¹, esmolol 200 μg · kg⁻¹ · min⁻¹, or landiolol 50 μg · kg⁻¹ · min⁻¹ (n = 6 in each group). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. Additional rats received esmolol 50 μg · kg⁻¹ · min⁻¹ or landiolol 10 μg · kg⁻¹ · min⁻¹ intrathecally (IT) via the cisterna magna (n = 5 in each group), according to the same experimental protocol. The neurological deficit score was evaluated at 22 h after reperfusion, and the brains were removed and stained with triphenyltetrazolium chloride for evaluation of infarct volume. Additional rats that received saline, esmolol, and landiolol IV (n = 6 in each group) were allowed to survive for 7 days followed by measurement of infarct size. Neurological deficit scores were smaller in rats treated with propranolol-IV, carvedilol-IV, esmolol-IV, landiolol-IV, esmolol-IT, and landiolol-IT compared with saline-treated rats (P < 0.05). Cortical and striatum infarct volumes were less in the rats receiving β-adrenoreceptor antagonists via either IV or IT than in saline-treated rats (P < 0.05). We conclude that β-adrenoreceptor antagonists improve neurological and histological outcomes after transient focal cerebral ischemia in rats independent of administration route.