1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan   430030, Hubei Province, China

2Department of Neurology, Shandong Provincial Hospital, Jinan   250021, Shandong Province, China

3Department of Pathology, Shandong Provincial Hospital, Jinan   250021, Shandong Province, China

Minzhong Wang☆, Doctor, Associate chief physician, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan   430030, Hubei Province, China; Department of Neurology, Shandong Provincial Hospital, Jinan   250021, Shandong Province, China Supported by: the Project of Shandong Provincial Health Department, No. 2007HW093*; the Project of Shandong Provincial Science and Technology Department, No. 003130103* Wang MZ, Lin XY, Liu XP, Fu QX, Zhang SM. Mild hypothermia effects on matrix metalloproteinase-9 expression in the perihematomal region of rats following experimental intracerebral hemorrhage. Neural Regen Res 2008;3(7):764-7

Abstract

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) expression increases with intracerebral hemorrhage, and participates in the pathophysiological processes of secondary brain injury after intracerebral hemorrhage.

OBJECTIVE: To investigate the effects of mild hypothermia on MMP-9 expression and brain edema in the perihematomal region of experimental intracerebral hemorrhage rats.

DESIGN, TIME AND SETTING: The randomized, controlled experiment was performed at the Central Laboratory of Shandong Provincial Hospital between May and September 2007.

MATERIALS: Seventy-two, Wistar, male rats, 12-weeks old, were used for this study. Rabbit anti-MMP-9 primary antibody was purchased from Boster, China.

METHODS: Wistar rats were equally and randomly divided into normothermia and mild hypothermia groups. The two groups each comprised control, 6-hour intracerebral hemorrhage, 24-hour intracerebral hemorrhage, 48-hour intracerebral hemorrhage, 72-hour intracerebral hemorrhage, and 1-week intracerebral hemorrhage subgroups, with six rats in each subgroup. Rat models of intracerebral hemorrhage were established by injecting 100 μL of autologous blood into the rat caudate nucleus. Rats in the mild hypothermia group received four hours of local mild hypothermia immediately following the injection. Intracerebral temperature was maintained at (33 ± 0.5) ℃. Subsequently, intracerebral temperature was spontaneously recovered at 25 ℃. Rats in the control subgroup were not injected with autologous blood and received only with intracerebral hemorrhage.

MAIN OUTCOME MEASURES: Brain water content and MMP-9 expression surrounding the hematoma region. 

RESULTS: MMP-9 expression increased at 6 hours, and brain edema reached a peak at 48 hours after intracerebral hemorrhage. MMP-9 expression was significantly decreased in the mild hypothermia group compared with the normothermia group at each time point (P < 0.05).

CONCLUSION: Mild hypothermia can significantly inhibit MMP-9 overexpression and relieve brain edema following intracerebral hemorrhage.

Key Words: intracerebral hemorrhage; mild hypothermia; brain edema; matrix metalloproteinases

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