Hypoxic-ischemic brain injury induces an acute microglial reaction in perinatal rats.
Activated microglia may contribute to the progression of neuronal injury after a wide range of CNS insults. In this study, we used two complementary methods to evaluate acute changes in the morphology and regional distribution of microglia induced by a focal hypoxic-ischemic insult in 7-d-old (P7) rats. To elicit injury, P7 rats underwent right carotid ligation followed by 3 h of 8% O2 exposure; rats were killed 10 min to 5 d later (n > or = 3/group). A histochemical assay using Griffonia simplicifolia B4-isolectin enabled detection of both resting and activated microglia in tissue sections; vascular cells were also reactive. Activated microglia were also identified immunocytochemically using a macrophage-specific MAb, ED-1. In normal P7-12 brain, lectin, and ED-1 immunoreactive-activated microglia were concentrated in white matter; lectin-positive resting, ramified microglia were also detected throughout the gray and white matter. Subtle morphologic evidence of microglial activation was noted 10 min posthypoxia-ischemia in the lesioned right cerebral hemisphere; activated microglia began to accumulate within the next 4 h. Accumulation of lectin-positive activated microglia peaked at 2-4 d posthypoxia-ischemia. ED-1 immunoreactive-microglia were first noted 4 h after hypoxic-ischemic injury in the lesioned right hemisphere, and there was a corresponding increase in accumulation over the first 48 h posthypoxia-ischemia. In the left hemisphere, contralateral to the ligation, no increase in activated microglia were detected with either method. In brain sections where no neuronal injury was evident, activated microglia did not accumulate. These data demonstrate that perinatal hypoxic-ischemic brain injury induced rapid accumulation of activated microglia in hypoxic-ischemic forebrain.
Ivacko
J A
JA
Department of Pediatrics and Neurology, University of Michigan, Ann Arbor 48109-0640, USA.
Sun
R
R
Silverstein
F S
FS
D000818:Animals; D000911:Antibodies, Monoclonal; D002534:Hypoxia, Brain / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology*; D037102:Lectins; D017628:Microglia / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D037102:Lectins