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Role of Fibrinogen in Traumatic Brain Injury
Author(s) -
Muradashvili Nino,
Tyagi Reeta,
Benton Richard L.,
Lominadze David
Publication year - 2013
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.27.1_supplement.1121.5
Subject(s) - penumbra , caveolae , fibrinogen , matrix metalloproteinase , mmp9 , medicine , traumatic brain injury , blood–brain barrier , vascular permeability , endothelium , endocrinology , pathology , chemistry , ischemia , cell , downregulation and upregulation , central nervous system , biochemistry , psychiatry , gene
Elevated level of fibrinogen (Fg) ‐ hyperfibrinogenemia (HFg) exacerbates circulatory complications during inflammatory diseases such as stroke, hypertension, traumatic brain injury (TBI). We already showed that HFg alters vascular reactivity and compromises endothelial cell layer integrity causing a leakage of plasma substances into the interstitium. We tested the hypothesis that TBI increases Fg deposition and cerebrovascular permeability in injury penumbra through activation of matrix metalloproteinase‐ 9 (MMP‐9). Permeability of pial venules and Fg deposition in injury penumbra formed after a mild cortical contusion injury (CCI) were studied in wild type (WT, C57BL/6J) and MMP‐9 gene knockout (MMP9−/−) mice. Fg deposition and formation of caveolae, examined by the extent of co‐localization of caveolin‐1 and plasmalemma vesicle‐associate protein‐1 were assessed in brain cryo‐sections. In each group, BSA leakage, caveolae formation, and Fg deposition were increased after CCI compared to those in respective sham‐operated mice. However, they were greater in WT than in MMP9−/− mice. These data suggest that blood level of Fg is elevated after TBI and its increased deposition intensifies cerebrovascular protein leakage mainly through caveolar transcytosis via activation of MMP‐9. The results of our study point to a new therapeutic targets that can be used to assist the post‐TBI healing process.