RAKERS et al
| Autor: | Cordula Rakers, Matthias Schmid, Gabor C. Petzold |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine metabolism [Stroke] Brain Edema Calcium in biology Brain Ischemia 0302 clinical medicine pathology [Brain] pathology [Neurons] genetics [Aquaporin 4] metabolism [Calcium] Trpv4 protein mouse pathology [Astrocytes] Neurons Mice Knockout metabolism [Astrocytes] metabolism [Brain Edema] genetics [TRPV Cation Channels] Penumbra pathology [Brain Edema] Brain Stroke Neurology metabolism [Neurons] Cerebrovascular Circulation Female TRPV4 P-type calcium channel metabolism [Brain Ischemia] TRPV Cation Channels Glutamic Acid chemistry.chemical_element Biology Calcium pathology [Brain Ischemia] physiology [Cerebrovascular Circulation] blood supply [Brain] 03 medical and health sciences Cellular and Molecular Neuroscience metabolism [TRPV Cation Channels] Animals ddc:610 Aquaporin 4 metabolism [Aquaporin 4] metabolism [Glutamic Acid] T-type calcium channel metabolism [Connexin 43] Aqp4 protein mouse Mice Inbred C57BL Disease Models Animal Electrophysiology 030104 developmental biology chemistry metabolism [Brain] Astrocytes Connexin 43 genetics [Connexin 43] pathology [Stroke] Membrane channel Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Glia 65(9), 1550-1561 (2017). doi:10.1002/glia.23183 Glia |
| ISSN: | 0894-1491 |
| DOI: | 10.1002/glia.23183 |
| Popis: | Stroke is one of the leading causes of death and long-term disability. In the penumbra, that is, the area surrounding the infarct core, peri-infarct depolarizations (PIDs) are accompanied by strong intracellular calcium elevations in astrocytes and neurons, thereby negatively affecting infarct size and clinical outcome. The dynamics of PIDs and the cellular pathways that are involved during PID formation and progression remain incompletely understood. We have previously shown that inositol triphosphate-gated calcium release from internal stores is a major component of PID-related astroglial calcium signals, but whether external calcium influx through membrane-localized channels also contributes to PIDs has remained unclear. In this study, we investigated the role of two astroglial membrane channels, transient receptor vanilloid 4 (TRPV4) channel and aquaporin-4 (AQP4). We combined in vivo multiphoton microscopy, electrophysiology as well as laser speckle contrast imaging with the middle cerebral artery occlusion stroke model. Using knockout mice and pharmacological inhibitors, we found that TRPV4 channels contribute to calcium influx into astrocytes and neurons and subsequent extracellular glutamate accumulation during PIDs. AQP4 neither influenced PID-related calcium signals nor PID-related edema of astrocyte somata. Both channels did not alter the dynamics, frequency and cerebrovascular response of PIDs in the penumbra. These data indicate that TRPV4 channels may represent a potential target to ameliorate the PID-induced calcium overload of astrocytes and neurons during acute stroke. |
| Databáze: | OpenAIRE |
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