Characterization of biaxial stretch as an in vitro model of traumatic brain injury to the blood-brain barrier

Hector Rosas-Hernandez, Elvis Cuevas, Claudia Escudero-Lourdes, Susan M. Lantz, Nancy P. Gomez-Crisostomo, Nasya M. Sturdivant, Kartik Balachandran, Syed Z. Imam, William Slikker, Merle G. Paule, Syed F. Ali

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Traumatic brain injury (TBI) is one of the major causes of disability in the USA. It occurs when external mechanical forces induce brain damage that causes deformation of brain tissue. TBI is also associated with alterations of the blood-brain barrier (BBB). Using primary rat brain microvascular endothelial cells as an in vitro BBB model, the effects of biaxial stretch were characterized at 5, 10, 15, 25, and 50% deformation using a commercially available system. The results were compared to the effects of mild and moderate TBI in vivo, induced by the weight-drop method in mice. In vitro, live/dead cells, lactate dehydrogenase (LDH) release, caspase 3/7 staining, and tight junction (TJ) protein expression were evaluated 24 h after a single stretch episode. In vivo, Evans blue extravasation, serum levels of S100β, and TJ protein expression were evaluated. Stretch induced a deformationdependent increase in LDH release, cell death, and activation of caspase 3/7, suggesting the induction of apoptosis. Interestingly, low magnitudes of deformation increased the expression of TJ proteins, likely in an attempt to compensate for stretch damage. High magnitudes of deformation decreased the expression of TJ proteins, suggesting that the damage was too severe to counteract. In vivo, mild TBI did not affect BBB permeability or the expression of TJ proteins. However, moderate TBI significantly increased BBB permeability and decreased the expression of these proteins, similar to the results obtained with a high magnitude deformation. These data support the use biaxial stretch as valuable tool in the study of TBI in vitro.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalMolecular Neurobiology
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Keywords

  • Biaxial stretch
  • Blood-brain barrier
  • In vitro models
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience
  • Neuroscience (miscellaneous)

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