Synergistic effect of cold mannitol and Na(+)/Ca(2+) exchange blocker on blood-brain barrier opening.
The precise mechanism of reversible opening of the blood-brain barrier (BBB) is elusive. Hyperosmotic mannitol at 1.4 to 1.6 M is commonly used for this purpose but intraarterial injection of such a hyperosmotic solution is known to have possible side effects on the brain. Cooling of the solution has recently been reported to have potential to open the BBB. The in situ brain perfusion technique with [(14)C]-sucrose was used first to quantify BBB permeability in rats after intraarterial injection of 1.1 M mannitol, which is less hyperosmotic than commonly used mannitol, at room temperature and at 4 degrees C. Mannitol at 4 degrees C produced an opening of the BBB but the duration of the opening was less than 30 min. We then investigated the effect of an Na(+)/Ca(2+) exchange blocker (KB-R7943) on this hypothermic BBB opening. KB-R7943 extended the BBB opening to 30 min without affecting the peak level of BBB permeability at 5 min. Simple manipulation of temperature can thus enhance the reversible BBB opening in mannitol and pharmacological manipulation of calcium dynamics works synergistically with hypothermic mannitol.
Ikeda
Mitsuru
M
Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki Cho, Chuo-Ku, Kobe, 650-0017, Japan.
Bhattacharjee
Abesh Kumar
AK
Kondoh
Takeshi
T
Nagashima
Tatsuya
T
Tamaki
Norihiko
N
D000818:Animals; D001158:Arteries / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D003080:Cold Temperature; D004357:Drug Synergism; D006982:Hypertonic Solutions / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013395:Sucrose / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D006982:Hypertonic Solutions; D019831:Sodium-Calcium Exchanger; D008353:Mannitol; D013395:Sucrose; D013890:Thiourea