DISTINCT CONTRIBUTION OF ASTROCYTIC AND NG2‑GLIAL TRPV4 TO ISCHEMIC BRAIN INJURY

Transient receptor potential vanilloid 4 (TRPV4) channels regulate volume homeostasis, mechanotransduction, and calcium signaling in glial cells, including astrocytes and NG2 glia. Our previous studies showed that global deletion of TRPV4 exacerbates ischemic brain injury; however, the specific roles of TRPV4 in different glial populations remain poorly understood. In this project, we employed conditional TRPV4 knock-out mouse models targeting astrocytes and NG2 glia (aTrpv4^-/-, nTrpv4^-/-) and subjected them to middle cerebral artery occlusion (MCAO) to investigate cell‑type‑specific post‑ischemic responses. Magnetic resonance imaging was used to quantify ischemic lesion volume, while immunohistochemistry was employed to assess the extent of gliosis and NG2‑glial proliferation at multiple time points following MCAO. In addition, calcium imaging and whole‑cell patch‑clamp recordings were performed to examine functional changes in astrocytes from aTrpv4^-/- mice under oxygen–glucose deprivation (OGD). Deletion of TRPV4 in either astrocytes or NG2 glia resulted in significantly enlarged ischemic lesions. In nTrpv4^-/- mice, proliferation of NG2 glia was markedly reduced; however, mature oligodendrocytes remained largely unaffected. Astrocyte‑specific TRPV4 deletion did not alter astrogliosis after MCAO; nevertheless, OGD experiments revealed impaired astrocytic swelling capacity and altered potassium currents in the absence of TRPV4. Together, these findings demonstrate that TRPV4 channels limit ischemic injury and modulate astrocyte and NG2‑glia responses during cerebral ischemia.
This project is funded by the Czech Academy of Sciences, Strategy AV21 (grant VP29). Zuzana Hermanova is supported by the Czech Academy of Sciences, Programme to Support Prospective Human Resources – Postdoctoral Fellows (grant L200392551).