| First Author | Wu LJ | Year | 2012 |
| Journal | Nat Neurosci | Volume | 15 |
| Issue | 4 | Pages | 565-73 |
| PubMed ID | 22388960 | Mgi Jnum | J:191259 |
| Mgi Id | MGI:5461304 | Doi | 10.1038/nn.3059 |
| Citation | Wu LJ, et al. (2012) The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. Nat Neurosci 15(4):565-73 |
| abstractText | Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke. |
