Effects of selective hypothermia on blood-brain barrier integrity and tight junction protein expression levels after intracerebral hemorrhage in rats

Biol Chem. 2013 Oct;394(10):1317-24. doi: 10.1515/hsz-2013-0142.


Hypothermia has neuroprotective effects on global cerebral ischemic injuries. However, its efficacy after intracerebral hemorrhage (ICH) is inconclusive. In this study, bacterial collagenase was used to induce ICH stroke in male Wistar rats. We assessed the effects of normothermia and 4 h of local hypothermia (~33.2°C) initiated 1, 6, or 12 h after collagenase infusion on hemorrhage volume and neurological outcomes. Following early cooling initiated after 1 h, blood-brain barrier (BBB) disruption and brain water content were tested. Furthermore, the expression levels of tight junction (TJ) proteins (claudin 5 and occludin) and the proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were determined using Western blotting, real-time quantitative PCR, and immunohistochemical staining at 1 and 3 d after ICH. Early local hypothermia tends to reduce hemorrhagic volume and neurological deficits, but the difference is not statistically significant compared with other groups. However, early hypothermia significantly reduces BBB disruption, edema formation, the expression levels of IL-1β and TNF-α, and the loss of TJ proteins. Together, these data suggest that local hypothermia is an effective treatment for edema formation and BBB disruption via the upregulation of TJ proteins and the suppression of TNF-α and IL-1β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blotting, Western
  • Cerebral Hemorrhage / physiopathology*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hyperthermia, Induced*
  • Immunohistochemistry
  • Interleukin-1beta / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Tight Junctions / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha