Neuroprotective effects of troxerutin and cerebroprotein hydrolysate injection on the neurovascular unit in a rat model of middle cerebral artery occlusion- through nitric oxide synthase regulation.

Cerebral ischemic stroke, caused by obstruction of the blood flow to the brain, initiates a complex cascade of pathophysiological changes. The aim of the present study was to assess the protective role and the underlying mechanism of troxerutin and cerebroprotein hydrolysate (TCH) injections for five days in rats subjected to middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats treated with either TCH or a vehicle (0.9% saline) via intraperitoneal injection were examined one or three days after MCAO. TCH alleviated neurological deficits and reduced infarct volume, innate immune response, blood-brain barrier destruction, and suppressed cell apoptosis. The therapeutic effects of TCH were achieved by diminished neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), and increased endothelial nitric oxide synthase (eNOS). Furthermore, L-NAME showed an inhibitory effect against TCH after MCAO on eNOS expression, NO and peroxynitrite production, neurobehavioral score, and infarct volume. The results indicate that injection of TCH has multifaceted neuroprotective effects against MCAO via regulation of the various NOS isoforms.