Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice
Background and PurposeIn 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 mid...
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| Format: | Article |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.00453/full |
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| author | Koji Tanaka Shoji Matsumoto Takeshi Yamada Ryo Yamasaki Makoto Suzuki Mizuho A. Kido Jun-Ichi Kira |
| author_facet | Koji Tanaka Shoji Matsumoto Takeshi Yamada Ryo Yamasaki Makoto Suzuki Mizuho A. Kido Jun-Ichi Kira |
| author_sort | Koji Tanaka |
| collection | DOAJ |
| description | Background and PurposeIn 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.MethodstMCAO 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.ResultsCompared 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.ConclusionThe 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. |
| first_indexed | 2024-12-13T09:09:38Z |
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| language | English |
| last_indexed | 2024-12-13T09:09:38Z |
| publishDate | 2020-05-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-dff2c70dc5954b06b6b7e8929df4618d2022-12-21T23:52:58ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-05-011410.3389/fnins.2020.00453514260Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout MiceKoji Tanaka0Shoji Matsumoto1Takeshi Yamada2Ryo Yamasaki3Makoto Suzuki4Mizuho A. Kido5Jun-Ichi Kira6Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Comprehensive Strokology, School of Medicine, Fujita Health University, Toyoake, JapanDepartment of Neurology, Saiseikai Fukuoka General Hospital, Fukuoka, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Pharmacology, Division of Molecular Pharmacology, Jichi Medical University, Shimotsuke, JapanDepartment of Anatomy and Physiology, Faculty of Medicine, Saga University, Saga, JapanDepartment of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanBackground and PurposeIn 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.MethodstMCAO 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.ResultsCompared 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.ConclusionThe 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.https://www.frontiersin.org/article/10.3389/fnins.2020.00453/fullischemic stroketransient receptor potential vanilloid 4knockout micebrain edemablood–brain barrier |
| spellingShingle | Koji Tanaka Shoji Matsumoto Takeshi Yamada Ryo Yamasaki Makoto Suzuki Mizuho A. Kido Jun-Ichi Kira Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice Frontiers in Neuroscience ischemic stroke transient receptor potential vanilloid 4 knockout mice brain edema blood–brain barrier |
| title | Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice |
| title_full | Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice |
| title_fullStr | Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice |
| title_full_unstemmed | Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice |
| title_short | Reduced Post-ischemic Brain Injury in Transient Receptor Potential Vanilloid 4 Knockout Mice |
| title_sort | reduced post ischemic brain injury in transient receptor potential vanilloid 4 knockout mice |
| topic | ischemic stroke transient receptor potential vanilloid 4 knockout mice brain edema blood–brain barrier |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.00453/full |
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