To examine the therapeutic effect of 4-(o-benzylphenoxy)-N-methylhutylamine hydrochloride (bifemelane) on neuronal ischemia-reperfusion injury, we evaluated the neurological score in gerbils subjected to unilateral common carotid occlusion. Using the neurological score method, we selected animals which showed stroke symptoms without seizures, because seizure activity can modify the neurological outcome. Just after the clip removal following 30 min of ischemia, 0.2 ml of either vehicle (0.9% saline, n = 10) or bifemelane (25 mg/kg, n = 10) was administered intraperitoneally. Then, the neurological score and the maximum inclination at which the gerbil could maintain its equilibrium were recorded at 5, 10, and 30 min, and 1, 2, 3, 6, and 24 hr after the insult. Animals were then decapitated and their brains were processed for immunohistochemical investigation. Treatment with bifemelane after reperfusion significantly improved the neurological score and motor function. Immunohistochemistry using an antibody for microtubule-associated protein 2 clearly demonstrated preservation of staining especially in the caudate-putamen in the animals treated with bifemelane. The present findings suggest a beneficial effect of bifemelane on neuronal ischemia-reperfusion injury, which may be common after cerebral ischemia.
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