4.6 Article

Blood-brain barrier permeability is positively correlated with cerebral microvascular perfusion in the early fluid percussion-injured brain of the rat

期刊

LABORATORY INVESTIGATION
卷 92, 期 11, 页码 1623-1634

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2012.118

关键词

blood brain barrier; MRI; rat; traumatic brain injury; vascular reactivity

资金

  1. National Science and Nature Committee of China [30973086]
  2. National Health Ministry of China [200802093]
  3. Shanghai Science and Technology Committee [10JC1409800]
  4. Program for Shanghai Outstanding Medical Academic Leader

向作者/读者索取更多资源

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 24h, and in the contralateral area at 24h 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 4h and significantly elevated at 12 and 24h as compared to that at 0 or 1 h after TBI. Our findings demonstrate that the 4h post trauma is a critical turning point during the development of TBI, and, importantly, the correlation analysis may guide us how to treat TBI. Laboratory Investigation (2012) 92, 1623-1634; doi:10.1038/labinvest.2012.118; published online 10 September 2012

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