Nitric oxide synthase immunoreactivity related to cold-induced brain edema.

To determine the relationship between brain edema and the expression of nitric oxide synthase (NOS), we immunohistochemically studied the distribution and level of NOS in rat brain cold injury model. Vasogenic brain edema was produced by cortical freezing lesion. NOS immunohistochemical studies were performed 4 and 8 h, 1, 3, 5, 7, 14 and 21 days after injury. In control normotensive rats, immunoreactivity for NOS was observed in scattered neuronal cells as reported previously, but there was no reactivity in glial cells. In the present study in the cold injury model, however, fibrinogen staining showed extravasated plasma fluid extending to the white matter contralateral to the site of cold injury. NOS immunoreactivity was observed in most reactive astrocytes and a proportion of the microglial cells and macrophages in the white matter not only just beneath the area of cold injury but also in the contralateral side. The nerve cells in the edematous region scarcely showed additional immunoreactivity for NOS. The distribution of increased NOS relatively corresponded with the sites of extravasated plasma fluid demonstrated by fibrinogen staining. Electron microscopically, NOS was observed in astrocytes along the rough endoplasmic reticulum suggesting that NOS was produced in the cells and not taken up from the surroundings. Based on these findings, we postulate that brain edema and the simultaneously generated free radicals or some extravasated plasma components may induce expression of NOS in the reactive cells, and that the NO thus generated may be involved in the development of diffuse degeneration of the white matter which accompanies brain edema.