Cellular inflammatory response associated with breakdown of the blood-brain barrier after closed head injury in rats

This study reports a widespread microglial response characterized by an upr egulation of surface antigens, such as complement type 3 receptors (CR3) an d major histocompatibility complex (MHC) class II antigens on these cells f ollowing closed head injury. Increased expression of CR3 (OX-42) and MHC cl ass II antigens (OX-6) was observed in rats killed at 1, 3, and 5 days afte r injury. Intense OX-42 immunoreactivity was observed in microglial cells t hroughout the brain with a smaller number of them being OX-6 positive. In a ddition to microglial reaction, astrocytic activation reflected in cellular hypertrophy and increased immunoreactivity for glial fibrillary acidic pro tein (GFAP) was observed at 5 days after head injury. Together with the abo ve, a diffuse perivascular and intraneuronal immunostaining for immunoglobu lin G (IgG) was observed primarily in the cerebral cortex. This was accompa nied by an enhanced expression of both endothelial nitric oxide synthase (e NOS) in blood vessels and inducible nitric oxide synthase (iNOS) in brain m acrophages. In rats subjected to closed head injury followed by a single in traperitoneal (i.p.) injection of rhodamine isothiocyanate (RhIc), seepage of the fluorescent dye into the neuropil was observed. This had resulted in the labelling of the cortical neurons dearly demonstrating a breakdown of the blood-brain barrier (BBB). In the latter, it is conceivable that the en suing leakage of plasma immunoglobulins and other serum-derived materials c ould induce the expression of MHC class II antigens on microglia. The mecha nism causing the BBB dysfunction is not clear, although present results sug gest that excessive release of nitric oxide (NO) may be a contributory fact or. The widespread activation of microglia in rats after head injury sugges ts their involvement in increased endocytosis and immunological responses.