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Role of NOS in early‐stage BBB disruption following transient focal cerebral ischemia
Author(s) -
Jiang Zheng,
Li Chun,
Arrick Denise M.,
Yang Shu,
Sun Hong
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.1121.2
Subject(s) - extravasation , ischemia , evans blue , papaverine , vasodilation , anesthesia , medicine , ligation , chemistry , pathology
Background Early‐stage BBB disruption following ischemic stroke is an antecedent event to infarction and hemorrhagic transformation. We determined the role of NOS in early‐stage BBB disruption using a new model of transient focal cerebral ischemia. Methods A cranial window was prepared over the left parietal and temporal cortex of C57BL/6J mice. To induce ischemia, the MCA was ligated at M2 segment just proximal to its bifurcation for 2 hours. Reperfusion was induced by releasing the ligation. L‐NAME, L‐NPA, 7‐NI and aminoguanidine alone or with papaverine were topically perfused to the cranial window during the reperfusion. The cerebral vasculature was imaged at 5, 10, 30, 60, 90, 120, 150 and 180 minutes of reperfusion and diameter change in all branches of the MCA, anastomosis and terminal branches of the collateral arteries were calculated. BBB disruption was assessed by measuring extravasation of Evans Blue (EB) and sodium fluorescein (Na‐F) at 3 hours of reperfusion. Results L‐NAME abolished reperfusion‐induced vasodilation in all branches of the MCA, anastomosis and terminal branches of the collateral arteries, whereas L‐NPA, 7‐NI and aminoguanidine only inhibited the vasodilation in large size branches of the MCA and anastomosis. On the other hand, L‐NAME, L‐NPA, 7‐NI and aminoguanidine all reduced extravasation of EB and Na‐F. In addition, papaverine abolished L‐NAME‐induced reduction in extravasation of Na‐F. Conclusions All three types of NOS may contribute to early‐stage BBB disruption directly and indirectly via NOS‐mediated hyperemia following transient focal cerebral ischemia.