Shigeki Ono    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Neurosurgery 2,    Position   Professor
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Antivasospastic and antiinflammatory effects of caspase inhibitor in experimental subarachnoid hemorrhage
Journal	Formal name：Journal of neurosurgery Abbreviation：J Neurosurg ISSN code：00223085/19330693
Volume, Issue, Page	107(1),pp.128-35
Author and coauthor	Iseda K, Ono S, Onoda K, Satoh M, Manabe H, Nishiguchi M, Takahashi K, Tokunaga K, Sugiu K, Date I.
Publication date	2007/07
Summary	OBJECT: Inflammation in the subarachnoid space and apoptosis of arterial endothelial cells have been implicated in the development of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). The authors investigated mechanisms of possible antivasospastic effects of N-benzyl-oxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), a caspase inhibitor that can inhibit both inflammatory and apoptotic systems, in animal models of SAH. METHODS: Rabbits were assigned to three groups of eight animals each and were subjected to SAH by injection of blood into the cisterna magna. The experiments were performed in the following groups: SA only, SAH + vehicle, and SAH + Z-VAD-FMK. The Z-VAD-FMK (1 mg) or vehicle (5% dimethyl sulfoxide) was intrathecally administered before SAH induction. Diameters of the basilar artery (BA) were measured on angiograms obtained before and 2 days after SAH. The BA diameter on Day 2 was expressed as a percentage of that before SAH. Interleukin (IL)-1 in the cerebrospinal fluid (CSF) was examined using Western blotting, and brains were immunohistochemically examined for caspase-1 and IL-1beta. In a separate experiment, 20 rats were subjected to SAH and their brains were immunohistochemically assessed for caspase-1, IL-1beta, and macrophages. RESULTS. In rabbits, Z-VAD-FMK significantly attenuated cerebral vasospasm (the BA diameter on Day 2 in SAH-only, SAH + vehicle, and SAH + Z-VAD-FMK groups was 66.6 +/- 3.2%, 66.3 +/- 3.7%, and 82.6 +/- 4.9% of baseline, respectively), and suppressed IL-1beta release into the CSF and also suppressed immunoreactivities of caspase-1 and IL-1P in macrophages infiltrating into the subarachnoid space. Immunoreactivities for caspase-1 and IL-1P were observed in immunohistochemically proven infiltrating macrophages in rats. CONCLUSIONS: These results indicate that caspase activation may be involved in the development of SAH-induced vasospasm through inflammatory reaction.
Document No.	17639882