Hyperthermia worsens ischaemic brain injury through destruction of microvessels in an embolic model in rats

Abstract

Purpose: Basal lamina is a major part of the microvascular wall and plays a critical role in the integrity of microvasculature. The aim of this study is to determine whether hyperthermia worsens the destruction of microvascular integrity in the ischaemic injured brain. Materials and methods: Focal cerebral ischaemia was induced by embolising a pre-formed clot into the middle cerebral artery (MCA). Rats received either normothermic or hyperthermic treatment. Neurological score and infarct size were evaluated at 24h after the MCA occlusion. Microvascular collagen type IV and laminin were measured with fluorescence microscopy. The activities of matrix metalloproteinases (MMP-2 and MMP-9) and plasminogen activators (tPA and uPA) were determined by zymography. Results: Treatment with hyperthermia significantly increased infarct volume (p<0.01), cortex swelling (p<0.01), striatum swelling (p<0.05) and neurologic score (p<0.01) at 24h after the MCA occlusion. Compared to the normothermic groups, hyperthermia significantly worsened the losses of microvascular basal lamina structure proteins, collagen type IV and laminin, at 6h (p<0.001) and 24h (p<0.01) after MCA occlusion. Hyperthermia increased the MMP-9 activity at 6 and 24h after MCA occlusion compared with normothermia (p<0.05), whereas increased the MMP-2 activity at 6h only (p<0.05). Hyperthermia also elevated uPA activity significantly at 6 and 24h after MCA occlusion compared to normothermia (p<0.05). Conclusions: These results demonstrate that hyperthermia exacerbates the destruction of microvascular integrity possibly by increasing the activities of MMP-2, MMP-9 and uPA in the ischaemic cerebral tissues. © 2012 Informa UK Ltd All rights reserved.