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

We examined the possible prophylactic potential of fasudil, a protein kinas e inhibitor, on the development of endothelial injury and neutrophil infilt ration after subarachnoid haemorrhage (SAH). Using the two haemorrhage cani ne model, fasudil (3 mg/kg) was infused intravenously for 30 min twice dail y (days 1-7) and related histological changes were observed by light and el ectron microscopy. On day 7 characteristic features of the basilar arteries included corrugation of the elastic lamina and endothelial disruption; fas udil inhibited this endothelial damage. Marked neutrophil infiltration into the subarachnoid space was not detected until day 3. On day 7 a large numb er of neutrophils was observed in the subarachnoid space around all the bas ilar arteries examined; fasudil treatment significantly inhibited neutrophi l infiltration. Our findings suggest that: (1) endothelial injury and neutr ophils 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 ev ents. (C) 1999 Harcourt Publishers Ltd.