Neuroprotective effect of Buyang Huanwu Decoction against focal cerebral ischemia/reperfusion injury in rats – Time window and mechanism

Buyang Huanwu Decoction, a traditional Chinese medicine, consists of different herbal medicines, and has been traditionally used for centuries to treat paralysis and stroke. However, its optimal therapeutic time window and the mechanism are still unclear. This study was designed to explore the therapeutic time window and mechanism of Buyang Huanwu Decoction on transient focal cerebral ischemia/reperfusion injury. Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats, and 40 g/kg of Buyang Huanwu Decoction was intragastrically infused at different time points, and the same dose was infused every 24 h for 3 days. The level of glutamate in cerebrospinal fluid and the expression of metabotropic glutamate receptor-1 RNA in striatum were detected before, during, and after ischemia/reperfusion. Neurological deficit scores and brain infarction volumes were measured at 72 h after reperfusion. Cerebral ischemia/reperfusion resulted in significant neurological deficit and extensive cerebral infarct volume, associated with a large amount of glutamate in cerebrospinal fluid and elevation of metabotropic glutamate receptor-1 RNA expression. Buyang Huanwu Decoction significantly suppressed the release of glutamate, and reduced the expression of metabotropic glutamate receptor-1 RNA. The neurological defect score and infarction volume were significantly improved by administration of Buyang Huanwu Decoction, when compared with the Ischemia group. Administration of Buyang Huanwu Decoction, within 4 h of post-transient focal stroke, reduced significant cerebral ischemia/reperfusion damage. The neuroprotective mechanism of Buyang Huanwu Decoction is, in part, associated with the down-regulation of metabotropic glutamate receptor-1 RNA and inhibition of glutamate release resulting from cerebral ischemia.