Induction of nitric oxide synthase by traumatic brain injury

We investigated the dynamic induction/expression of inducible nitric oxide synthase (iNOS) using human brains made available through death by traumatic brain injury (TBI). Astrocytes, microglia, and neutrophils were identified in tissue using immunohistochemical staining with antibodies against glial fibrillary acidic protein (GFAP), MHC class II antigen, and neutrophil elastase, respectively. The localization of iNOS protein in each of these cell types was evaluated using immunohistochemistry. Within 2 days of injury, iNOS immunoreactivity was not detected. However, after 2 days, immunoreactivity was detected in the traumatized brain. The iNOS immunoreactivity was localized on neutrophils and microglia/macrophages in the areas around the tissue necrosis in the traumatized cortical hemisphere, in the deep part of the cortex and the dentate gyri of the hippocampi adjacent to the hemorrhage, and within the cytoplasm of vascular smooth muscle cell of a small artery or arteriole surrounding the injured region. This reactivity was absent after 8 days post-injury. These observations confirmed the prolonged induction of iNOS within various cells in the injured brain. These responses suggest that iNOS plays a crucial role in cerebrovascular damage and/or secondary brain damage subsequent to traumatic brain injury. Furthermore, the dense nitric oxide (NO) generated by iNOS may play a role in neuronal cell death after injury.