Peripheral thermal injury causes blood-brain barrier dysfunction and matrix metalloproteinase (MMP) expression in rat

Kathryn Swann, Jamie Berger, Shane M. Sprague, Yimin Wu, Qin Lai, David F. Jimenez, Constance M. Barone, Yuchuan Ding

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Mortality after serious systemic thermal injury may be linked to significant increases in cerebral vascular permeability and edema due to blood-brain barrier (BBB) breakdown. This BBB disruption is thought to be mediated by a family of proteolytic enzymes known as matrix metalloproteinases (MMPs). The gelatinases, MMP-2 and MMP-9, digest the endothelial basal lamina of the BBB, which is essential for maintaining BBB integrity. The current study investigated whether disruption of microvascular integrity in a rat thermal injury model is associated with gelatinase expression and activity. Seventy-two adult Sprague-Dawley rats were anesthetized and submerged horizontally, in the supine position, in 100 °C (37 °C for controls) water for 6 s producing a third-degree burn affecting 60-70% of the total body surface area. Brain edema was detected by calculating water content. Real time PCR, Western blot, and zymography were used to quantify MMP mRNA, protein, and enzyme activity levels. Each group was quantified at 3, 7, 24, and 72 h post thermal injury. Brain water content was significantly increased 7 through 72 h after burn. Expression of brain MMP-9 mRNA was significantly increased as early as 3 h after thermal injury compared to controls, remained at 7 h (p < 0.01), and returned to control levels by 24 h. MMP-9 protein levels and enzyme activity began to increase at 7 h and reached significant levels between 7 and 24 h after thermal injury. While MMP-9 protein levels continued to increase significantly through 72 h, enzyme activity returned to control level. The increase in MMP-9 expression and activity, associated with increased BBB permeability following thermal injury, indicates that MMP-9 may contribute to observed cerebral edema in peripheral thermal injury.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
JournalBrain Research
Volume1129
Issue number1
DOIs
StatePublished - Jan 19 2007

Keywords

  • Blood-brain barrier
  • Burn
  • Cerebral edema
  • MMP-2
  • MMP-9
  • Thermal injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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  • Cite this

    Swann, K., Berger, J., Sprague, S. M., Wu, Y., Lai, Q., Jimenez, D. F., Barone, C. M., & Ding, Y. (2007). Peripheral thermal injury causes blood-brain barrier dysfunction and matrix metalloproteinase (MMP) expression in rat. Brain Research, 1129(1), 26-33. https://doi.org/10.1016/j.brainres.2006.10.061