[Forensic pathological significance of iNOS with regard to brain and myocardial damage]

Inducible nitric oxide synthase (iNOS) does not express within cells under normal conditions. But, it is induced by inflammatory cytokines and the activity of iNOS is independent of elevated Ca2+. It is implied that nitric oxide (NO) produced by iNOS has a close relation with pathological conditions as a mediator of cell damages. We aimed at the crucial property of iNOS, therefore we have searched the expression of iNOS for the purpose to establish forensic pathological significance in the cases with damages of neuronal cells or cardiomyocytes. At first, we examined induction and expression of iNOS in the human brains whose causes of death was traumatic brain injury (TBI). These findings demonstrated prolonged induction of iNOS in neutrophils, microglia/macrophages, and vascular smooth muscle cells in traumatized brain. Such a response may indicate that iNOS could play a crucial role on cerebrovascular disturbances and secondary brain injury subsequent to TBI. Secondly, we evaluated the induction and expression of iNOS in the human hearts with myocardial cell damage. The expressions of iNOS were localized to the following areas, the cardiomyocytes in the zone adjacent to the infarcted area, the preserved cytoplasm of infarcted cardiomyocytes, the endothelial cells in arteriolar walls and macrophages in viable myocardium. These findings have led to the speculation that the NO might play a significant role during myocardial ischemia and reperfusion. Furthermore, representative expression of iNOS was identified in coronary artery, that is the portion of shoulder and broken part of coronary atherosclerotic plaque. These findings may indicate that the iNOS might have a close relation to the coronary atherosclerotic lesion. The physiopathological mechanism of iNOS might involve in the close relation with inflammatory cytokines. The precise elucidation of this participation may make it possible to explicate the presumed time of injury in an earlier stage, and to clarify the forensic pathological significance of these inflammatory factors.