title: 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. Copyright 1999 Harcourt Publishers Ltd.
authors.affiliation: Laboratory for Pharmacology, Asahi Chemical Industry, Tagata, Japan
authors.initials: Si
authors.lastname: Satoh
authors.initials: Y
authors.lastname: Yamamoto
authors.initials: Y
authors.lastname: Toshima
authors.initials: I
authors.lastname: Ikegaki
authors.initials: T
authors.lastname: Asano
authors.initials: Y
authors.lastname: Suzuki
authors.initials: M
authors.lastname: Shibuya