title: MMP-9 and EBA immunoreactivity after papaverine mediated opening of the blood-brain barrier.
abstract: Papaverine is a non-specific vasodilatory drug, which was found to unexpectedly cause opening of the blood-brain barrier (BBB). We studied the expression of two endothelial cell related markers, endothelial barrier antigen (EBA) as a marker of BBB intactness, and matrix metalloproteinase-9 (MMP-9), an extracellular matrix molecule, the activation of which results in BBB opening. Immunoreactivity was quantified after intra-carotid injection of papaverine in rats. BBB opening was identified at 1 h, but had been reversed by 24 h. Reduction in EBA-immunoreactivity occurred at 3 h, whereas MMP-9 was not observed until 24 h. The activation of MMP-9 thus occurred much later than BBB opening, which suggests a different role for MMP-9 when selective and reversible opening of the BBB is produced by pharmacological manipulation.
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki Cho, Chuo-Ku, Kobe 650-0017, Japan. tkondo@med.kobe-u.ac.jp
authors.forename: Abesh Kumar
authors.initials: AK
authors.lastname: Bhattacharjee
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondoh
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ikeda
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohmura
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000187:drug effects* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology; D004058:Diffusion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology*; D005070:Evans Blue; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects* / Q000201:enzymology*; D010208:Papaverine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology
chemical_list: D000954:Antigens, Surface; C114781:endothelial barrier antigen, rat; D005070:Evans Blue; D010208:Papaverine; D020780:Matrix Metalloproteinase 9