Quantitative analysis of papaverine-mediated blood-brain barrier disruption in rats.
The blood-brain barrier (BBB) is a permeability barrier of interconnected brain capillary endothelial cells. Intraarterial infusion of papaverine relieves cerebral vasospasms by inhibiting smooth muscle contractions and it may simultaneously lead to a disruption of BBB permeability. To date, the mechanism underlying this phenomenon and the quantification of BBB disruption remains elusive. We first examined the changes in cerebrovascular permeability after an intracarotid infusion of papaverine (0.20%) in rats by an in situ brain perfusion technique. We then demonstrated that changes in cerebrovascular permeability depend on the concentration of papaverine. This is the first study in which the degree of BBB disruption was accurately quantified in terms of [(14)C]sucrose and it was demonstrated that papaverine has a prolonged effect on cerebrovascular permeability. This result suggests the importance of in vivo experiments for a precise evaluation of permeability for many other agents, particularly for the central nervous system.
Bhattacharjee
A K
AK
Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki Cho, Chuo-Ku, Kobe 650-0017, Japan.
Kondoh
T
T
Nagashima
T
T
Ikeda
M
M
Ehara
K
K
Tamaki
N
N
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism; D010208:Papaverine / Q000378:metabolism*; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D013395:Sucrose; D010208:Papaverine