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 24 h 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 24 h 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 6 h (p < 0.001) and 24 h (p < 0.01) after MCA occlusion. Hyperthermia increased the MMP-9 activity at 6 and 24 h after MCA occlusion compared with normothermia (p < 0.05), whereas increased the MMP-2 activity at 6 h only (p < 0.05). Hyperthermia also elevated uPA activity significantly at 6 and 24 h 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.