Inducible nitric oxide synthase: a possible key factor in the pathogenesisof chronic vasospasm after experimental subarachnoid hemorrhage

Object. The role of nitric oxide (NO) in the pathogenesis of cerebral vasos pasm after subarachnoid hemorrhage (SAH) is not well understood, Nitric oxi de is a well-established vasodilatory substance: however, in SAH, NO may be come a major source for the production of injurious free-radical species, l ending to chronic cerebral vasospasm, Reactive overproduction of NO to coun teract vascular narrowing might potentiate the detrimental effects of NO. T he focus of the present study is to determine the extent of reactive induct ion of inducible nitric oxide synthase (iNOS) after experimental SAH. Methods. Chronic vasospasm was induced in male Wistar rats by an injection of autologous blood (100 mu l) into the cisterna magna followed by a second injection 24 hours later. A control group of 10 animals was treated with i njections of 0.9% sodium chloride solution. Vasospasm was verified by press ure-controlled angiography after retrograde cannulation of the external car otid artery 7 days later. In 11 of 15 animals radiographic evidence of cere bral vasospasm was seen. The animals were perfusion fixed and their brains were removed for immunohistochemical assessment. With the aid of a microsco pe, staining for iNOS was quantified in 40-mu m floating coronal sections. Immunohistochemical staining for iNOS was markedly more intense in animals with significant angiographic evidence of vasospasm. Virtually no staining was observed in control animals. Seven days after the second experimental S AH, labeling of iNOS was found in endothelial cells, in vascular smooth-mus cle cells, and, above all, in adventitial cells. Some immunohistochemical s taining of iNOS was observed in rod cells (activated microglia), in glial n etworks, and in neurons. Conclusions. The present study demonstrates induction of iNOS after experim ental SAH.