title: Early exercise protects the blood-brain barrier from ischemic brain injury via the regulation of MMP-9 and occludin in rats.
abstract: Early exercise within 24 h after stroke can reduce neurological deficits after ischemic brain injury. However, the mechanisms underlying this neuroprotection remain poorly understood. Ischemic brain injury disrupts the blood-brain barrier (BBB) and then triggers a cascade of events, leading to secondary brain injury and poor long-term outcomes. This study verified the hypothesis that early exercise protected the BBB after ischemia. Adult rats were randomly assigned to sham, early exercise (EE) or non-exercise (NE) groups. The EE and NE groups were subjected to ischemia induced by middle cerebral artery occlusion (MCAO). The EE group ran on a treadmill beginning 24 h after ischemia, 30 min per day for three days. After three-days' exercise, EB extravasation and electron microscopy were used to evaluate the integrity of the BBB. Neurological deficits, cerebral infarct volume and the expression of MMP-9, the tissue inhibitors of metalloproteinase-1 (TIMP-1), and occludin were determined. The data indicated that early exercise significantly inhibited the ischemia-induced reduction of occludin, and an increase in MMP-9 promoted TIMP-1 expression (p < 0.01), attenuated the BBB disruption (p < 0.05) and neurological deficits (p < 0.01) and diminished the infarct volume (p < 0.01). Our results suggest that the neuroprotection conferred by early exercise was likely achieved by improving the function of the BBB via the regulation of MMP-9 and occludin.
authors.affiliation: Department of Rehabilitation of Huashan Hospital, Fudan University, Shanghai 200040, China. dr_huys@yahoo.com.cn.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pengyue
authors.initials: P
authors.lastname: Zhang
authors.forename: Xiafeng
authors.initials: X
authors.lastname: Shen
authors.forename: Shan
authors.initials: S
authors.lastname: Tian
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Yulian
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Jia
authors.forename: Junfa
authors.initials: J
authors.lastname: Wu
authors.forename: Yongshan
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000648:ultrastructure; D001930:Brain Injuries / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000201:enzymology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D062793:Occludin / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D062793:Occludin; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9