Hypoxic-ischemic brain injury stimulates glial fibrillary acidic protein mRNA and protein expression in neonatal rats.

Accumulation of glial fibrillary acidic protein xk(G-FAP) in reactive astrocytes is a characteristic neuropathologic feature of ischemic brain injury. We examined injury-induced changes in GFAP mRNA and protein in a well-characterized model of focal hypoxic-ischemic injury in perinatal rodent brain. Postnatal Day (PND) 7 rats underwent right carotid artery ligation followed by 2.5 h exposure to 8% oxygen, which results in injury to ipsilateral cortex, hippocampus, and striatum in the majority of animals. Using Northern analysis, we assayed GFAP mRNA in samples from the lesioned and contralateral hemispheres of animals killed 1 h to 14 days later, and from animals treated with the neuroprotective glutamate antagonist MK-801. GFAP immunoreactivity in tissue homogenates from the lesioned and contralateral hemispheres was also compared with an immunoblot assay. One and 4 h posthypoxia GFAP mRNA expression was barely detectable. In the lesioned cortex, increased GFAP mRNA was detected at 24 h postinjury; over the next 2 weeks GFAP mRNA was consistently higher (at least 2-fold) in lesioned than in contralateral cortex. In contrast, in lesioned hippocampus and striatum, consistent increases in GFAP mRNA were first detected on PND 12. Immunoassays of GFAP demonstrated early (PND 8) and sustained (to PND 21) up to 10-fold increases in lesioned cortex, hippocampus, and striatum. In this perinatal stroke model regionally specific increases in GFAP mRNA expression and GFAP immunoreactivity are detected in the first 2 weeks after hypoxic-ischemic injury; intrinsic properties of glia and/or neurons in different brain regions may influence the timing and magnitude of stimulation of this response.