J Korean Neurol Assoc > Volume 21(4); 2003 > Article

Journal of the Korean Neurological Association 2003;21(4): 378-386.

"국소 뇌허혈에서 뇌저온 요법이 허혈 손상 및 Matrix Metalloproteinase 활성도에 미치는 영향"

이경열 , 김은희 김경환 허지회 이병인 선우일남

연세대학교 의과대학 신경과학교실 신촌세브란스병원, 영동세브란스병원 신경과학교실*

"Effect of Brain Hypothermia on Ischemic Injury and Matrix Metalloproteinase Activity in Focal Cerebral Ischemia"

Kyung Yul Lee

"Department of Neurology, Shinchon Severance Hospital and Yongdong Severance Hopspital* Yonsei University College of Medicine"

Abstract

"Background: Effects of hypothermia have been demonstrated in experimental animals with cerebral ischemia. Although the exact mechanisms of hypothermic effects are unknown, decrease of the blood－brain barrier (BBB) permeability, inhibition of free radical generation, and anti-inflammatory actions have been suggested. Matrix metalloproteinases (MMPs) may play a role in the hypothermic effect because they are known to mediate neuro-inflammatory responses and BBB breakdown. M e t h o d s: The rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) and 18 hours of reperfusion. The normothermia group was maintained at 37℃. Moderate hypothermia was induced by maintaining the temperature at 32℃ during MCAO in the intra-ischemic hypothermia (IH) group, and for 2 hours immediately after reperfusion in the postischemic hypothermia (PH) group. The infarction size in coronal slices were measured after 2,3,5-triphenyltetrazolium chloride stain. By gelatin zymography, the activity of MMP-2 and MMP-9 was measured. Evans blue extravasation methods were used to determine the BBB disruption.
Results: The infarction size was significantly decreased in the IH group compared to the normothermia group. The MMP-2 and MMP-9 activities in the ischemic hemispheres was significantly decreased in the IH group compared to the normothermia group. In the PH group, only the MMP-2 activity was significantly decreased compared to the normothermia group. Infarction size was significantly correlated with MMP-2 (r=0.688), and MMP-9 (r=0.707) activities. The disruption of BBB was significantly reduced in the IH group compared to the normothermia group. C o n c l u s I o n s: Intra-ischemic hypothermia effectively attenuated ischemic injury. Hypothermia-mediated inhibition of MMP-2 and MMP-9 activities may contribute to this protective effect. Key Words: Cerebral infarction, Hypothermia, Matrix metalloproteinase, Blood-brain barrier"