Neuronal death and survival in two models of hypoxic-ischemic brain damage

Two unilateral hypoxic-ischemia (HI) models (moderate and severe) in immatu re rat brain have been used to investigate the role of various transcriptio n factors and related proteins in delayed neuronal death and survival. The moderate HI model results in an apoptotic-like neuronal death in selectivel y vulnerable regions of the brain while the more severe HI injury consisten tly produces widespread necrosis resulting in infarction, with some necrosi s resistant cell populations showing evidence of an apoptotic type death. I n susceptible regions undergoing an apoptotic-like death there was not only a prolonged induction of the immediate early genes, c-jun, c-fos and nur77 , but also of possible target genes amyloid precursor protein (APP(751)) an d CPP32. In contrast, increased levels of BDNF, phosphorylated CREB and PGH S-2 were found in cells resistant to the moderate HI insult suggesting that these proteins either alone or in combination may be of importance in the process of neuroprotection. An additional feature of both the moderate and severe brain insults was the rapid activation and/or proliferation of glial cells (microglia and astrocytes) in and around the site of damage. The gli al response following HI was associated with an upregulation of both the CC AAT-enhancer binding protein alpha (microglia only) and NF kappa B transcri ption factors. (C) 1999 Elsevier Science B.V. All rights reserved.