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Early Post‐Ischemic Blood‐Brain Barrier (BBB) Disruption in Obesity
Author(s) -
Li Chun,
Jiang Zheng,
Arrick Denise M,
Lu Wei,
McCarter Kimberly D,
Sun Hong
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.953.11
Subject(s) - blood–brain barrier , extravasation , evans blue , ischemia , medicine , endocrinology , cerebral cortex , nitric oxide , nitric oxide synthase , cortex (anatomy) , middle cerebral artery , anesthesia , pathology , central nervous system , biology , neuroscience
We determined the effect of high fat diet (HFD)‐induced obesity on early BBB disruption following transient focal cerebral ischemia. Male C57BL/6J mice were fed a HFD or standard chow for 16 weeks. A cranial window was prepared over the left frontal, parietal and temporal cortex. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Early BBB disruption was assessed by measuring Evans Blue and sodium fluorescein extravasation at 3 hours of reperfusion. The body weight was significantly increased in obesity group (49.2 ± 0.4g) compared to control group (31.9 ± 0.6g). There was no significant difference in conscious blood pressure and fasting blood glucose between control and obesity groups. Transient focal cerebral ischemia produced an early BBB disruption in both control and obesity groups. However, the magnitude of early BBB disruption was significantly greater in obesity group compared to control group. Topical treatment with L‐NPA, 7‐NI (neuronal nitric oxide synthase inhibitors) or L‐NAME (a nonspecific nitric oxide synthase inhibitor) completely abolished the BBB disruption in control group, but only partially suppressed the BBB disruption in obesity group. Interestingly, matrix metallopeptidase (MMP)‐9 activity of cerebral cortex was reduced in obesity group either under basal conditions or following ischemic stroke. Our findings suggest that obesity exacerbates early post‐ischemic BBB disruption via a mechanism that appears to be unrelated to MMP‐9 or NOS.