Hyperthermia up-regulates matrix metalloproteinases and accelerates basement membrane degradation in experimental stroke

Abstract

Increased body temperature results in severe neuronal damage during cerebral ischemia. We hypothesized that hyperthermia hastens the degradation of basement membrane protein components and causes the disruption of brain microvasculature through early up-regulation of matrix metalloproteinases (MMPs). In this study, we present data from both non-ischemic and ischemic hemispheres of stroke induced rat brain. We found that the expression of MMP-2 and -9 and degradation of laminin and collagen IV were significantly increased in the ischemic hemisphere when compared with the non-ischemic hemisphere after 24h of normothermic stroke (p<0.001). No significant increase in MMPs expression and basement membrane components degradation was observed after 4h of normothermic stroke. At 4h, hyperthermia increased the expression of MMP-2 and -9 and subsequent degradation of laminin and collagen IV at the level that was comparable to normothermic stroke after 24h and significantly higher than 4h of normothermic stroke (p<0.001). The early increase in MMPs may be an important contributing factor to the severe neuronal damage evident with hyperthermia during an ischemic stroke.