COORDINATE CHANGES IN BRAIN ENERGY METABOLISM AND PROTEIN SYNTHESIS

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Changes in brain energy metabolism and protein synthesis have been characterized following transient bilateral ischemia in the gerbil. Analysis of in vitro translation products by two dimensional gel electrophoresis has demonstrated the induction of the major mammalian stress-induced or heat shock protein, (hsp 70), during recifulation following 5 min ischemis. Expression of hsp 70 increases gradually following recirculation, reaching a maximum at approximately 8 hr recirculation, and returns to near control levels by 24 hr. In contrast, the synthesis of all other individual proteins exzamined fell dramatically following ischemia and returned to control levels in parallel with the recovery of overall incorporation activity. This transient induction of hsp 70 resembles the classical heat-shock response defined on other systems, although at no time does hsp 70 become a major translation product. A low level of hsp 70 synthesis is detected in preparations from control brain, and the protein can be found in silver stained gels of control brain proteins. Preliminary immunohistochemical localization of hsp 70 indicates its presence in essentially all neuronal cell bodies. Preliminary radioimmunoassay data have demonstrated a 30% depletion of the opiate peptide, dynorphin A, in gerbil cerebal hemispheres between 1 and 24 hr following 5 min ishchemia. Beta-endorphin and met-enkephalin levels were not affected by ischemia, although the gerbil population used in these studies appears to be quite heterogenous with regard to beta-endorphin levels in brain. These observations may be relevant to the conflicting reports of effects of opiate antagonists on stroke symptoms in this animal model.