β-Adrenoreceptor antagonists attenuate brain injury following transient focal ischemia in rats

Introduction

β-adrenoreceptor antagonists experimentally reduce cardiac and renal injury following ischemia, and also are clinically useful for myocardial infarction ¹ and severe burn ² . In addition, β-adrenoreceptor antagonists have neuroprotective effects in focal cerebral ischemia in experimental settings ³ . The present study was conducted to compare the neuroprotective effects of several β-adrenoreceptor antagonists in the rat transient focal cerebral ischemia.

Methods

Halothane anesthetized normothermic adult male Sprague-Dawley rats (280 – 320 g) were subjected to 2 hr of middle cerebral artery occlusion (MCAO) using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received intravenous (iv) infusion of saline 1 ml/hr, propranolol 100 μg/kg/min, carvedilol 4 g/kg/min, esmolol 200 g/kg/min, or landiolol 50 g/kg/min (n=6 in each group). Infusion was initiated 30 min prior to MCAO and continued for 24 hr. Additional rats received esmolol 50 g/kg/min, or landiolol 10 g/kg/min intrathecally (it) via cisterna magna (n=6 in each group), according to the same experimental protocol. The neurological deficit score was evaluated at 24 hr after reperfusion, and the brains were removed and stained with TTC. Data (mean±SD) were analyzed by ANOVA, with P<0.05 being significant.

Results

Neurological deficit scores were smaller in the rats treated with propranolol-iv (15. 3 ± 3.7), carvedilol-iv (13.6 ± 3.3), esmolol-iv (11.3 ± 6.1), landiolol-iv (9.1 ± 4.0), esmolol-it (3.6 ± 4.3), and landiolol-it (10.6 ± 1.3), compared to saline-treated rats (27.5 ± 9.8)(P<0.05). The infarct volumes of cortical and striatum were less in the rats receiving -adrenoreceptor antagonists irrespective of administration route, than in saline-treated rats (P<0.05, figure 1).

Figure 1

Conclusion

We conclude that administration of -adrenoreceptor antagonists improves neurological and histological outcome following transient focal cerebral ischemia in rats. In particular, short acting -adrenoreceptor antagonists provide neuroprotection independent of administration route.