Department of Neurology, Third Xiangya Hospital, Central South University, Changsha   410083, Hunan Province, China

Lifang Lei☆, Studying for doctorate, Attending physician, Department of Neurology, Third Xiangya Hospital, Central South University, Changsha   410083, Hunan Province, China   Leilifang119@sina.com Supported by: the Natural Science Foundation of Hunan Province, No. 04JJ6015*, 06JJ50062* Lei LF, Zi XH, Tu QY. Matrix metalloproteinase 9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury. Neural Regen Res 2008;3(5):505-8

Abstract

BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injury

OBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.

DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.

MATERIALS: Ninety healthy male SD rats, aged 3–4 months, weighing 200–280 g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.

METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3, 6, 12 hours, 1, 2, 4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.

MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.

RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it gradually decreased. 

CONCLUSION: MMP-9 expression increases in rat brain tissue after focal cerebral ischemia/reperfusion injury, which correlates with increased permeability of the BBB.

Key Words: ischemia/reperfusion injury; matrix metalloproteinase-9; blood brain barrier

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