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- Title
Deficiency in the voltage-gated proton channel Hv1 increases M2 polarization of microglia and attenuates brain damage from photothrombotic ischemic stroke.
- Authors
Tian, Dai‐Shi; Li, Chun‐Yu; Qin, Chuan; Murugan, Madhuvika; Wu, Long‐Jun; Liu, Jun‐Li
- Abstract
Microglia become activated during cerebral ischemia and exert pro-inflammatory or anti-inflammatory role dependent of microglial polarization. NADPH oxidase ( NOX)-dependent reactive oxygen species ( ROS) production in microglia plays an important role in neuronal damage after ischemic stroke. Recently, NOX and ROS are consistently reported to participate in the microglial activation and polarization; NOX2 inhibition or suppression of ROS production are shown to shift the microglial polarization from M1 toward M2 state after stroke. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent ROS generation in the brain. However, the effect of Hv1 proton channel on microglial M1/M2 polarization state after cerebral ischemia remains unknown. In this study, we investigated the role of microglial Hv1 proton channel in modulating microglial M1/M2 polarization during the pathogenesis of ischemic cerebral injury using a mouse model of photothrombosis. Following photothrombotic ischemic stroke, wild-type mice presented obvious brain infarct, neuronal damage, and impaired motor coordination. However, mice lacking Hv1 (Hv1−/−) were partially protected from brain damage and motor deficits compared to wild-type mice. These rescued phenotypes in Hv1−/− mice in ischemic stroke is accompanied by reduced ROS production, shifted the microglial polarization from M1 to M2 state. Hv1 deficiency was also found to shift the M1/M2 polarization in primary cultured microglia. Our study suggests that the microglial Hv1 proton channel is a unique target for modulation of microglial M1/M2 polarization in the pathogenesis of ischemic stroke.
- Subjects
MICROGLIA; ACTIVE oxygen in the body; BRAIN damage; STROKE; MOVEMENT disorders
- Publication
Journal of Neurochemistry, 2016, Vol 139, Issue 1, p96
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.13751