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Transient receptor potential vanilloid type 4 channels mediate Na‐K‐Cl‐co‐transporter‐induced brain edema after traumatic brain injury
Author(s) -
Lu KwokTung,
Huang TaiChun,
Tsai YaHsin,
Yang YiLing
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13920
Subject(s) - trpv4 , bumetanide , mapk/erk pathway , traumatic brain injury , hippocampal formation , transient receptor potential channel , edema , protein kinase b , medicine , pharmacology , endocrinology , chemistry , phosphorylation , receptor , biochemistry , ion transporter , membrane , psychiatry
Na + ‐K + ‐2Cl − co‐transporter ( NKCC 1) plays an important role in traumatic brain injury ( TBI )‐induced brain edema via the MAPK cascade. The transient receptor potential vanilloid type 4 ( TRPV 4) channel participates in neurogenic inflammation, pain transmission, and edema. In this study, we investigated the relationship between NKCC 1 and TRPV 4 and the related signaling pathways in TBI ‐induced brain edema and neuronal damage. TBI was induced by the calibrated weight‐drop device. Adult male Wistar rats were randomly assigned into sham and experimental groups for time‐course studies of TRPV 4 expression after TBI . Hippocampal TRPV 4, NKCC 1, MAPK , and PI ‐3K cascades were analyzed by western blot, and brain edema was also evaluated among the different groups. Expression of hippocampal TRPV 4 peaked at 8 h after TBI , and phosphorylation of the MAPK cascade and Akt was significantly elevated. Administration of either the TRPV 4 antagonist, RN 1734, or NKCC 1 antagonist, bumetanide, significantly attenuated TBI ‐induced brain edema through decreasing the phosphorylation of MEK , ERK , and Akt proteins. Bumetanide injection inhibited TRPV 4 expression, which suggests NKCC 1 activation is critical to TRPV 4 activation. Our results showed that hippocampal NKCC 1 activation increased TRPV 4 expression after TBI and then induced severe brain edema and neuronal damage through activation of the MAPK cascade and Akt‐related signaling pathway.