Fasudil, a protein kinase inhibitor, prevents the development of endothelial injury and neutrophil infiltration in a two-haemorrhage canine subarachnoid model

Abstract

We examined the possible prophylactic potential of fasudil, a protein kinase inhibitor, on the development of endothelial injury and neutrophil infiltration after subarachnoid haemorrhage (SAH). Using the two haemorrhage canine model, fasudil (3 mg/kg) was infused intravenously for 30 min twice daily (days 1–7) and related histological changes were observed by light and electron microscopy. On day 7 characteristic features of the basilar arteries included corrugation of the elastic lamina and endothelial disruption; fasudil inhibited this endothelial damage. Marked neutrophil infiltration into the subarachnoid space was not detected until day 3. On day 7 a large number of neutrophils was observed in the subarachnoid space around all the basilar arteries examined; fasudil treatment significantly inhibited neutrophil infiltration. Our findings suggest that: (1) endothelial injury and neutrophils play a major role in the pathogenesis of cerebral vasospasm; and (2) fasudil inhibited both endothelial damage and neutrophil infiltration, and therefore protein kinase pathways may have a role in these pathological events.