title: Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.
abstract: The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB) disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV) not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Arrick
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Baluna
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000473:pathology*; D002560:Cerebrovascular Circulation; D054022:Cerebrum / Q000098:blood supply / Q000201:enzymology; D005070:Evans Blue / Q000378:metabolism; D019793:Fluorescein / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000201:enzymology; D014664:Vasodilation
chemical_list: D005456:Fluorescent Dyes; D005070:Evans Blue; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D019793:Fluorescein