HEME OXYGENASE-1 IS INDUCED IN GLIA THROUGHOUT BRAIN BY SUBARACHNOID HEMOGLOBIN

The heme oxygenase-1 gene, HO-1, induced by heme, ischemia, and heat s hock, metabolizes heme to biliverdin, free iron, and carbon monoxide. Though the distribution of HO-1 has been described in normal rat brain , little is known about how extracellular heme proteins in the subarac hnoid space distribute in brain. To address this issue, hemoglobin was injected into the cisterna magna of adult rats. Expression of HO-1 in these animals was compared with saline-injected, BSA-injected, and un injected controls. Western blot analysis showed that 24 hours after in jection oxyhemoglobin increased HO-1 levels approximately four-to five fold in all brain regions studied compared with saline-injected and BS A-injected controls. In the brain, HO-1 immunoreactivity was evident a t 4 hours and peaked at 24 hours after oxyhemoglobin injections, retur ning to control levels by 4 to 8 days. This HO-1 induction was detecte d mainly in cells with small, rounded somas bearing two to four trunca ted processes, a morphology consistent with that of microglia. These c ells were double-stained with the microglial marker, OX42, in every br ain region examined. II is proposed that subarachnoid hemoglobin may b e taken up into a microglia wherein heme induces HO-1.