2014 Volume 7 Issue 1 Pages 34a
Although it has been known that brain generates carbon monoxide (CO) via heme oxygenase (HO) catalyzed reactions, physiologic roles of CO in the central nervous system remain elusive. Previous study showed that HO-2 generates CO in an O2-dependent manner. By acting as an acute O2 sensor within the neurovascular unit, HO-2 contributes to the maintenance of cerebral ATP levels against acute global hypoxia (Morikawa et al., PNAS, 109, 1293-1298). In this study, we examined if the deletion of HO-2 exacerbates cerebral metabolism upon acute focal brain ischemia. We compared contents of 87 metabolites extracted from contralateral- and ipsilateral hemispheres after a left middle cerebral artery occlusion (MCAO) between wild-type- and HO-2-null mice. With hierarchical clustering analysis, we found that, in ipsilateral hemispheres, there was no obvious difference in patterns of metabolic alteration between wild-type- and HO-2-null mice. On the other hand, in the contralateral hemispheres, we found the clusters showed striking difference in patterns of metabolic alteration between two groups during MCAO. Such a cluster included high energy phosphonucleotides; e.g., ATP, UTP and CTP. These data indicate that nucleotide degradation after MCAO is more severe in the HO-2-null mice than that in wild-type mice. Furthermore, our results indicate that HO-2 contributes to the improvement of metabolic disorders during cerebral ischemia in contralateral hemisphere rather than in ipsilateral hemisphere. This is the first report showing the potency of HO-2/CO system to diminish the remote metabolic insults of acute focal cerebral ischemia.
