Abstract
Neurovascular coupling (NVC) allows increased blood flow to metabolically active neurons and involves the Ca2+-dependent release of vasodilator influences by astrocyte endfeet that encase parenchymal arterioles. We previously reported inversion of NVC from dilation to constriction in brain slices from subarachnoid hemorrhage (SAH) model rats. Corresponding to NVC inversion, there was a marked increase in the amplitude of spontaneous Ca2+ oscillations in astrocyte endfeet. Calcium-permeable transient receptor potential vanilloid (TRPV)-4 channels have been reported in astrocyte endfeet, and activators of these channels enhance Ca2+ oscillations in healthy animals. Here, we examined the role of TRPV4 channels in the development of high-amplitude spontaneous Ca2+ oscillations in astrocyte endfeet and the inversion of neurovascular coupling after SAH. Treatment of brain slices with the TRPV4 channel antagonist, HC-067047 (10 μM), did not alter the amplitude of spontaneous Ca2+ oscillations after SAH. In addition, HC-067047 did not inhibit or change SAH-induced inversion of neurovascular coupling. In summary, TRPV4 channels do not appear to be involved in the inversion of neurovascular coupling after SAH. Further studies examining the impact of SAH on additional Ca2+ signaling pathways in astrocytes are likely to reveal valuable insights into new therapeutic strategies to advance SAH treatments.
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Acknowledgments
This work was supported by the Totman Trust for Medical Research, the Peter Martin Brain Aneurysm Endowment, and the NIH (P01 HL095488, R01 HL078983 and R01 HL078983-05S1). The authors also acknowledge the use and assistance of the University of Vermont Neuroscience COBRE imaging core facility (NIH P30 GM103498 and S10 OD 010583) and input from Drs. Mark T. Nelson and Kathryn M. Dunn.
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We declare that we have no conflict of interest.
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Koide, M., Wellman, G.C. (2015). Activation of TRPV4 Channels Does Not Mediate Inversion of Neurovascular Coupling After SAH. In: Fandino, J., Marbacher, S., Fathi, AR., Muroi, C., Keller, E. (eds) Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 120. Springer, Cham. https://doi.org/10.1007/978-3-319-04981-6_19
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