Hemeoxygenase expression after reversible ischemia of rat brain.

Heme oxygenase (HO-1) gene expression was studied in the brains of rats subjected to 30 min global cerebral ischemia followed by recirculation of up to 24 h. Total RNA was isolated from the cerebral cortex, striatum and hippocampus and reverse-transcribed into cDNA. cDNA was taken as template for PCR using HO-1-specific primers. We found that, when PCR reactions were run for 22 cycles, the amount of PCR products correlated closely with the amount of cDNA. HO-1 gene expression was sharply increased after cerebral ischemia in all three brain structures studied. In the cortex and striatum, the HO-1 mRNA content increased constantly after cerebral ischemia up to 24 h of recovery, being 8- and 9-fold over control after 24 h of recirculation in the cortex and striatum, respectively. In the hippocampus, HO-1 mRNA levels peaked at 4 h after ischemia (9-fold over control) and declined thereafter to 4.5-fold over control 24 h after ischemia. Assuming that the observed increase in mRNA levels is paralled by increased HO-1 protein synthesis, formation of the products of HO reaction, biliverdin and carbon monoxide, is activated after ischemia. These products may produce different and divergent effects on the recovery from the metabolic stress produced by cerebral ischemia.