| First Author | Tanaka K | Year | 2020 |
| Journal | Front Neurosci | Volume | 14 |
| Pages | 453 | PubMed ID | 32477057 |
| Mgi Jnum | J:288935 | Mgi Id | MGI:6433518 |
| Doi | 10.3389/fnins.2020.00453 | Citation | Tanaka K, et al. (2020) Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice. Front Neurosci 14:453 |
| abstractText | Background and Purpose: In the acute phase of ischemia-reperfusion, hypoperfusion associated with ischemia and reperfusion in microvascular regions and disruption of the blood-brain barrier (BBB) contribute to post-ischemic brain injury. We aimed to clarify whether brain injury following transient middle cerebral artery occlusion (tMCAO) is ameliorated in Transient receptor potential vanilloid 4 knockout (Trpv4(-/-) ) mice. Methods: tMCAO was induced in wild-type (WT) and Trpv4(-/-) mice aged 8-10 weeks. Ischemia-induced lesion volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining at 24 h post-tMCAO. Tissue water content and Evans blue leakage in the ipsilateral hemisphere and a neurological score were evaluated at 48 h post-tMCAO. Transmission electron microscopy (TEM) was performed to assess the morphological changes in microvasculature in the ischemic lesions at 6 h post-tMCAO. Results: Compared with WT mice, Trpv4(-/-) mice showed reduced ischemia-induced lesion volume and reduced water content and Evans blue leakage in the ipsilateral hemisphere alongside milder neurological symptoms. The loss of zonula occludens-1 and occludin proteins in the ipsilateral hemisphere was attenuated in Trpv4(-/-) mice. TEM revealed that parenchymal microvessels in the ischemic lesion were compressed and narrowed by the swollen endfeet of astrocytes in WT mice, but these effects were markedly ameliorated in Trpv4(-/-) mice. Conclusion: The present results demonstrate that TRPV4 contributes to post-ischemic brain injury. The preserved microcirculation and BBB function shortly after reperfusion are the key neuroprotective roles of TRPV4 inhibition, which represents a promising target for the treatment of acute ischemic stroke. |
