Traumatic brain injury in vivo and in vitro contributes to cerebral vascular dysfunction through impaired gap junction communication between vascular smooth muscle cells

Guang Xiang Yu, Martin Mueller, Bridget E. Hawkins, Babu P. Mathew, Margaret A. Parsley, Leoncio A. Vergara, Helen L. Hellmich, Donald S. Prough, Douglas S. Dewitt

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Gap junctions (GJs) contribute to cerebral vasodilation, vasoconstriction, and, perhaps, to vascular compensatory mechanisms, such as autoregulation. To explore the effects of traumatic brain injury (TBI) on vascular GJ communication, we assessed GJ coupling in A7r5 vascular smooth muscle (VSM) cells subjected to rapid stretch injury (RSI) in vitro and VSM in middle cerebral arteries (MCAs) harvested from rats subjected to fluid percussion TBI in vivo. Intercellular communication was evaluated by measuring fluorescence recovery after photobleaching (FRAP). In VSM cells in vitro, FRAP increased significantly (p<0.05vs. sham RSI) after mild RSI, but decreased significantly (p<0.05vs. sham RSI) after moderate or severe RSI. FRAP decreased significantly (p<0.05vs. sham RSI) 30min and 2h, but increased significantly (p<0.05vs. sham RSI) 24h after RSI. In MCAs harvested from rats 30min after moderate TBI in vivo, FRAP was reduced significantly (p<0.05), compared to MCAs from rats after sham TBI. In VSM cells in vitro, pretreatment with the peroxynitrite (ONOO-) scavenger, 5,10,15,20-tetrakis(4- sulfonatophenyl)prophyrinato iron[III], prevented RSI-induced reductions in FRAP. In isolated MCAs from rats treated with the ONOO- scavenger, penicillamine, GJ coupling was not impaired by fluid percussion TBI. In addition, penicillamine treatment improved vasodilatory responses to reduced intravascular pressure in MCAs harvested from rats subjected to moderate fluid percussion TBI. These results indicate that TBI reduced GJ coupling in VSM cells in vitro and in vivo through mechanisms related to generation of the potent oxidant, ONOO-.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalJournal of neurotrauma
Volume31
Issue number8
DOIs
StatePublished - Apr 15 2014

Keywords

  • cell culture
  • fluid percussion injury
  • gap junctions
  • middle cerebral arteries
  • rapid stretch injury
  • smooth muscle cells
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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