Peripheral thermal injury causes early blood–brain barrier dysfunction and matrix metalloproteinase expression in rat

Abstract

High mortality incidence after serious systemic thermal injury is believed to be linked to significant increases in cerebral permeability, ultimately leading to irreversible blood–brain barrier (BBB) breakdown. The aim of this study was to investigate whether disruption of microvascular integrity in a rat thermal injury model is associated with early matrix metalloproteinase (MMP) expression.

A total of 35 Sprague–Dawley rats were studied in thermal injury and control groups, each group containing two subgroups, one for brain edema and Evans blue analysis and another for MMP mRNA analysis. Thermally injured animals were anesthetized and submerged vertically in 85°C water to the neck for 6 seconds producing a third degree burn affecting 70% of the total body surface area. BBB integrity was determined by measuring amount of Evans blue after 7 hours of injury with a spectrophotometer. Brain edema was detected by calculating water content. Brain mRNA levels were determined with real-time PCR 3 and 7 hours post-injury.

Brain water content was significantly increased after peripheral injury at hour 7. Evans blue leakage was also significantly increased at the same time, suggesting an impaired BBB function after injury. Expressions of MMP-2 and MMP-9 mRNA in brain were increased as early as 3 hours after injury and remained at hour 7.

Our study demonstrated a significant increase in cerebral permeability that occurs after serious systemic thermal injury. The underlying mechanisms could be related to early expression of MMPs.