Transient receptor potential vanilloid type 4 channels mediate Na-K-Cl-co-transporter-induced brain edema after traumatic brain injury

Kwok Tung Lu, Tai Chun Huang, Ya Hsin Tsai, Yi Ling Yang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Na+-K+-2Cl co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the MAPK cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission, and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 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 TRPV4 expression after TBI. Hippocampal TRPV4, NKCC1, MAPK, and PI-3K cascades were analyzed by western blot, and brain edema was also evaluated among the different groups. Expression of hippocampal TRPV4 peaked at 8 h after TBI, and phosphorylation of the MAPK cascade and Akt was significantly elevated. Administration of either the TRPV4 antagonist, RN1734, or NKCC1 antagonist, bumetanide, significantly attenuated TBI-induced brain edema through decreasing the phosphorylation of MEK, ERK, and Akt proteins. Bumetanide injection inhibited TRPV4 expression, which suggests NKCC1 activation is critical to TRPV4 activation. Our results showed that hippocampal NKCC1 activation increased TRPV4 expression after TBI and then induced severe brain edema and neuronal damage through activation of the MAPK cascade and Akt-related signaling pathway. (Figure presented.).

Original languageEnglish
Pages (from-to)718-727
Number of pages10
JournalJournal of Neurochemistry
Volume140
Issue number5
DOIs
Publication statusPublished - 2017 Mar 1

Keywords

  • NKCC1
  • TRPV4
  • brain edema
  • mitogen-activated protein kinases cascade
  • traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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