Neurovascular protection in voltage ‐gated proton channel Hv1 knock‐out rats after ischemic stroke: interaction with Na+/H+ exchanger‐1 antagonism

The goal of the current study was to determine whether neurovascular injury and functional outcomes after experimental stroke differed in wild ‐type and Hv1 mutant Dahl salt‐sensitive rats treated with an NHE‐1 inhibitor. Our data indicate that Hv1 deletion confers both neuronal and vascular protection after ischemia in rats. These data are important as they build on previous reports in mice identifying Hv1 as a potential novel targe t for the treatment of stroke. AbstractExperimental studies have demonstrated protective effects of NHE ‐1 inhibition on cardiac function; however, clinical trials utilizing NHE‐1 antagonists found an increase in overall mortality attributed to thromboembolic strokes. NADPH oxidase‐derived reactive oxygen species (ROS) from microglial cells have been shown to contribute to injury following strok e. We have recently demonstrated that NHE‐1 inhibition enhances ROS in macrophages in a Hv1‐dependent manner. As Hv1 protein is highly expressed in microglia, we hypothesized that “NHE‐1 inhibition may augment neurovascular injury by activating Hv1,” providing a potential mechanism for the deleterious effects of NHE‐1. The goal of this study was to determine whether neurovascular injury and functional outcomes after experimental stroke differed in wild‐type and Hv1 mutant Dahl salt‐sensitive rats treated with an NHE‐1 inhibitor. Stroke was induced using both transient and per manent of middle cerebral artery occlusion (MCAO)....
Source: Physiological Reports - Category: Physiology Authors: Tags: Original Research Source Type: research