title: Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms.
abstract: OBJECTIVE
  The rupture of a cerebral aneurysm is a major cause of subarachnoid hemorrhage, but the mechanism of its development remains unclear. Inducible nitric oxide synthase (iNOS) is expressed in human and rat cerebral aneurysms, and aminoguanidine, a relatively selective inhibitor of iNOS, can decrease the number of the aneurysms in rats. In this study we applied our new mouse model of cerebral aneurysms to the iNOS gene knockout mice and observed experimental cerebral aneurysms in these animals to elucidate the role of iNOS in the process of cerebral aneurysm formation.
  
  
  METHODS
  Eight C57/Bl6 mice and 16 iNOS knockout mice received a cerebral aneurysm induction procedure. Four months after the operation, the mice were killed, their cerebral arteries were dissected, and the region of the bifurcation of the anterior cerebral artery/olfactory artery was examined histologically and immunohistochemically.
  
  
  RESULTS
  No significant difference was seen in the incidence of cerebral aneurysms between iNOS+/+ and iNOS-/- mice. However, the size of advanced cerebral aneurysms and the number of apoptotic smooth muscle cells were significantly greater in iNOS+/+ mice than in iNOS-/- mice.
  
  
  CONCLUSIONS
  Inducible NOS is not necessary for the initiation of cerebral aneurysm. However, the results of this study suggest that regulation of iNOS may have therapeutic potential in the prevention of the progression of cerebral aneurysms.
authors: Department of Neurosurgery, Kyoto University, Graduate School of Medicine, Japan.
authors: Nobutake
authors: N
authors: Sadamasa
authors: Kazuhiko
authors: K
authors: Nozaki
authors: Nobuo
authors: N
authors: Hashimoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure / Q000235:genetics; D002452:Cell Count; D002536:Cerebral Arteries / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II
chemical_list: D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse