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Cerebral microvascular dysfunction and inflammation following venous sinus thrombosis in mice.
Author(s) -
Nagai Mutsumi,
Terao Satoshi,
Yilmaz Gokhan,
Granger D. Neil
Publication year - 2008
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.22.1_supplement.1151.6
Subject(s) - evans blue , medicine , superior sagittal sinus , edema , cerebral venous sinus thrombosis , blood–brain barrier , vascular permeability , inflammation , thrombus , pathology , cerebral edema , thrombosis , anesthesia , central nervous system
Blood brain barrier (BBB) dysfunction and brain edema are major consequences of cerebral venous sinus thrombosis (CVST) that underlie the poor clinical outcome in patients with this condition. However, relatively little is known about the mechanisms that link CVST to this vasogenic edema. We have developed a murine model of CVST wherein BBB permeability, brain water content, and leukocyte‐endothelial cell adhesion (LECA) can be monitored at different times (3–48 hrs) following thrombus formation. A cranial window was created over the superior sagittal sinus (SSS) of C57Bl/6 mice. CVST was induced by placing a ferric chloride (20%) soaked 6‐0 silk suture onto the SSS for 5 minutes. The adhesion of rhodamine‐6G labeled leukocytes, BBB permeability to Evans blue, and water content were measured. Brain edema was observed at 48 hr, but not 3 hr, after CVST. Both BBB permeability and LECA were increased at both 3 and 48 hrs following CVST. At least one refluxing cortical vein was noted in 3 of 5 mice in the 48‐hr group. More LECA was noted in these venules with retrograde (reflux) perfusion. Our findings indicate that CVST can be reproducibly induced in mouse brain, with an increased BBB permeability and brain edema that characterizes the human condition. The CVST‐induced increases in BBB permeability and edema are accompanied by LECA, suggesting a possible role for inflammation in these responses. (P01 DK43785)