Koide Masayo, Wellman George C
Department of Pharmacology, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, USA,
Acta Neurochir Suppl. 2015;120:111-6. doi: 10.1007/978-3-319-04981-6_19.
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.
神经血管耦合（NVC）可使代谢活跃的神经元的血流增加，涉及由包裹实质小动脉的星形胶质细胞终足通过钙离子依赖方式释放血管舒张因子。我们之前报道过，在蛛网膜下腔出血（SAH）模型大鼠的脑片中，神经血管耦合从舒张转变为收缩。与神经血管耦合的转变相对应，星形胶质细胞终足中自发钙离子振荡的幅度显著增加。据报道，星形胶质细胞终足中存在钙通透性瞬时受体电位香草酸亚型（TRPV）-4通道，在健康动物中，这些通道的激活剂可增强钙离子振荡。在此，我们研究了TRPV4通道在SAH后星形胶质细胞终足中高幅度自发钙离子振荡的发展以及神经血管耦合转变中的作用。用TRPV4通道拮抗剂HC-067047（10 μM）处理脑片，并未改变SAH后自发钙离子振荡的幅度。此外，HC-067047并未抑制或改变SAH诱导的神经血管耦合转变。总之，TRPV4通道似乎不参与SAH后神经血管耦合的转变。进一步研究SAH对星形胶质细胞中其他钙离子信号通路的影响，可能会为推进SAH治疗的新治疗策略提供有价值的见解。
