Regional alterations of ATP and heat-shock protein-72 mRNA following hypoxia-ischemia in neonatal rat brain.

Neonatal rats, 7 days of age, underwent unilateral carotid artery ligation followed by exposure to hypoxia (8% O2) for 80 min. At the end of the period of hypoxia, and after recovery for 2 or 24 h, regional levels of ATP and heat-shock protein-72 (hsp72) mRNA were measured in adjacent brain sections using ATP-luminescence histochemistry and in situ hybridization, respectively. At the end of hypoxia, ATP levels were decreased in a patchy pattern within the hemisphere ipsilateral to the carotid ligation. In the parietal cortex, the reduction of ATP often occurred in columns oriented perpendicular to the cortical surface. Expression of hsp72 mRNA was not detected prior to recovery, except in the ventricular lining of the ipsilateral hemisphere. However, by 2 h of recovery, hsp72 mRNA was expressed in a diffuse pattern in the ipsilateral hemisphere, even in regions in which the distribution of ATP remained patchy. Although the regional extent of expression varied in different animals, hsp72 mRNA was expressed consistently in the subcortical white matter, which, in some animals, was the only region showing expression. In contrast to the diffuse pattern of expression at 2 h of recovery, expression of hsp72 mRNA at 24 h was highly localized in the superficial layers of cerebral cortex and the pyramidal cell layer of hippocampus. The present results demonstrate that hypoxia-ischemia causes regionally distinct alterations in ATP and hsp72 mRNA that may be related to cell injury in this model.