Excitotoxic injury stimulates glial fibrillary acidic protein mRNA expression in perinatal rat brain.
To study the molecular mechanisms contributing to glial fibrillary acidic protein (GFAP) accumulation after neuronal injury in the developing brain, we used a reproducible and pharmacologically modifiable model of excitotoxic injury, intracerebral injection of N-methyl-D-aspartate (NMDA) in Postnatal Day 7 rats. Injection of NMDA into the posterior striatum elicits dose-dependent ipsilateral injury to striatum, hippocampus, and overlying cortex; treatment with the non-competitive NMDA antagonist MK-801 is neuroprotective. To examine regionally specific changes in GFAP mRNA expression after lesioning, GFAP mRNA content was assayed, by Northern analysis, in pooled tissue samples of striatum, hippocampus, and cortex, derived from the injected and contralateral hemispheres of animals killed 1-16 days after lesioning with NMDA (12.5 nmol), and in samples derived from lesioned animals and littermates treated with MK-801. In addition, in situ hybridization assays were done to visualize the anatomic distribution of GFAP mRNA expression in NMDA-lesioned (n = 5) and lesioned/MK-801-treated animals (n = 3) 5 days postinjection. There was a marked rise in GFAP mRNA in lesioned cortex within 24 h, and increases were sustained over the next 2 weeks. In contrast, in striatum and hippocampus, in which severe histologic damage evolves, at 24 h postlesioning there was little stimulation of GFAP mRNA expression. Subsequently, 5-16 days postinjury increases in GFAP mRNA were detected in both brain regions. In animals examined 5 days postlesioning, MK-801 treatment markedly attenuated stimulation of GFAP mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of Michigan, Ann Arbor 48109-0570.
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Burtrum
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Silverstein
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D017403:In Situ Hybridization; D016202:N-Methylaspartate; D051381:Rats
D005904:Glial Fibrillary Acidic Protein; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate