title: Blood-brain barrier permeability is positively correlated with cerebral microvascular perfusion in the early fluid percussion-injured brain of the rat.
abstract: The blood-brain barrier (BBB) opening following traumatic brain injury (TBI) provides a chance for therapeutic agents to cross the barrier, yet the reduction of the cerebral microvascular perfusion after TBI may limit the intervention. Meanwhile, optimizing the cerebral capillary perfusion by the strategies such as fluid administration may cause brain edema due to the BBB opening post trauma. To guide the TBI therapy, we characterized the relationship between the changes in the cerebral capillary perfusion and BBB permeability after TBI. First, we observed the changes of the cerebral capillary perfusion by the intracardiac perfusion of Evans Blue and the BBB disruption with magnetic resonance imaging (MRI) in the rat subjected to lateral fluid percussion (FP) brain injury. The correlation between two variables was next evaluated with the correlation analysis. Since related to BBB breakdown, matrix metalloproteinase-9 (MMP-9) activity was finally detected by gelatin zymography. We found that the ratios of the perfused microvessel numbers in the lesioned cortices were significantly reduced at 0 and 1 h post trauma compared with that in the normal cortex, which then dramatically recovered at 4 and 24 h after injury, and that the BBB permeability was greatly augmented in the ipsilateral parts at 4, 12, and 24 h, and in the contralateral area at 24 h after injury compared with that in the uninjured brain. The correlation analysis showed that the BBB permeability increase was related to the restoration of the cerebral capillary perfusion over a 24-h period post trauma. Moreover, the gelatin zymography analysis indicated that the MMP-9 activity in the injured brain increased at 4 h and significantly elevated at 12 and 24 h as compared to that at 0 or 1 h after TBI. Our findings demonstrate that the 4 h post trauma is a critical turning point during the development of TBI, and, importantly, the correlation analysis may guide us how to treat TBI.
authors.affiliation: Department of Neurological Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Pan
authors.forename: Mingliang
authors.initials: M
authors.lastname: Wang
authors.forename: Xianjian
authors.initials: X
authors.lastname: Huang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Yin
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Jia
authors.forename: Wenhao
authors.initials: W
authors.lastname: Xiong
authors.forename: Nu
authors.initials: N
authors.lastname: Zhang
authors.forename: Ji-yao
authors.initials: JY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology*; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D005070:Evans Blue; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005070:Evans Blue; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat