In this study we examined the temporal response of microglia and macro
phages to mild head injury in the rat. Microglia and macrophages were
identified by their distinct morphology and by immunophenotype. With r
egard to the latter, antibodies to OX42 and ED1 were used to define mi
croglia and macrophages, respectively. Although there was no change in
the morphology of brain macrophages after mild head injury, the morph
ology of microglia was dramatically altered. Microglial cell bodies ap
peared larger with a more elaborate arborization of cellular processes
. After head injury certain populations of macrophages and microglia w
ere more intensely immunostained. By 3 days postinjury these intensely
stained cells exhibited a characteristic distribution in the brain. P
rominently stained microglia were detected in the thalamus, hippocampu
s, lateral and medial geniculate body, and the substantia nigra. Inten
sely stained macrophages were located primarily in tbe cortex and suba
rachnoid space adjacent to the site of impact. By 7 days postinjury in
tensely immunostained macrophages and microglia were widespread throug
hout the injured cortex. These results demonstrate that microglia and
macrophages are sensitive to mild head injury. Early changes in the ma
crophage population are more directly correlated with the most damaged
tissue and may reflect migration of these cells from either the subar
achnoid space or across the damaged blood-brain barrier. The early wid
espread microglial response in regions exhibiting no overt neuronal ce
ll damage suggests that these cells are responding to more subtle fact
or(s) that are expressed in the mildly traumatized brain.