This study reports a widespread microglial response characterized by an upregulation of
surface antigens, such as
complement type 3 receptors (CR3) and major histocompatibility complex (MHC)
class II antigens on these cells following
closed head injury. Increased expression of CR3 (OX-42) and MHC
class II antigens (OX-6) was observed in rats killed at 1, 3, and 5 days after injury. Intense OX-42 immunoreactivity was observed in microglial cells throughout the brain with a smaller number of them being OX-6 positive. In addition to microglial reaction, astrocytic activation reflected in cellular
hypertrophy and increased immunoreactivity for
glial fibrillary acidic protein (GFAP) was observed at 5 days after
head injury. Together with the above, a diffuse perivascular and intraneuronal immunostaining for
immunoglobulin G (
IgG) was observed primarily in the cerebral cortex. This was accompanied by an enhanced expression of both
endothelial nitric oxide synthase (eNOS) in blood vessels and
inducible nitric oxide synthase (iNOS) in brain macrophages. In rats subjected to
closed head injury followed by a single intraperitoneal (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 clearly demonstrating a breakdown of the blood-brain barrier (BBB). In the latter, it is conceivable that the ensuing leakage of plasma
immunoglobulins and other serum-derived materials could induce the expression of MHC
class II antigens on microglia. The mechanism causing the BBB dysfunction is not clear, although present results suggest that excessive release of
nitric oxide (NO) may be a contributory factor. The widespread activation of microglia in rats after
head injury suggests their involvement in increased endocytosis and immunological responses.