Protective Effect of Buflomedil in a Rat Model of Moderate Cerebral Ischemia

Abstract

Buflomedil hydrochloride (CAS 55837-25-7) is a vasoactive drug with a variety of pharmacodynamic properties. Although a number of studies have been carried out to verify the beneficial effect of buflomedil in ischemic peripheral conditions, few data are reported to justify the efficacious employment of buflomedil in the treatment of cerebrovascular diseases. The aim of the present study was to better investigate the neuroprotective effect of buflomedil in normal pentobarbital-anaesthetized rats subjected to transient bilateral common artery occlusion (BCO) for 20 min. Buflomedil hydrochloride (10 mg/kg) was administered by slow intravenous infusion (90 min), starting 1 h after the onset of ischemia. The rats were sacrificed 48 h after carotid clamping. BCO caused dramatic death of hippocampal CA1 pyramidal neurons, and a significant increase in circulating levels of neuron-specific enolase (NSE) and lactate. Treatment with buflomedil attenuated ischemia-induced histological loss and damage of CA1 pyramidal cells. Furthermore, in ischemic rats, the drug restored blood lactate concentrations and serum NSE concentrations to near normal levels. These data clearly demonstrate that buflomedil is able to protect brain neurons against damage following moderate global cerebral ischemia. One could speculate that this protective effect could be related to the capability of buflomedil to improve cerebral blood flow and energy metabolism, or to a smooth muscle relaxant effect on cerebral blood vessels.