The effects of the Na(+)/Ca(++) exchange blocker on osmotic blood-brain barrier disruption

Brain Research
A K BhattacharjeeN Tamaki

Abstract

Osmotic disruption of the blood-brain barrier (BBB) by mannitol is currently being used to enhance drug delivery in human brains. Despite clinical and experimental interest, to date the time course in the early phase of disruption has not been accurately identified. The mechanism in barrier closure also remains elusive. We first studied the rapid change in cerebrovascular permeability after BBB disruption in rats, and then demonstrated that the Na(+)/Ca(++) exchange blocker (KB-R7943) prolongs osmotic disruption. Osmotic BBB disruption was attained by using intra-arterial infusion of hypertonic mannitol in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate containing [14C]-sucrose was infused intra-arterially at different time points following osmotic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. This is the first in vivo study demonstrating that osmotic disruption is prolonged by the Na(+)/Ca(++) exchange blocker, which did not affect the peak level of BBB disruption. The exact time course of cerebrovascular reversibility was studied and the earliest BBB disruption was seen to occur 5 min after osmotic stress. Histopathological examin...Continue Reading

Citations

Aug 23, 2008·Anesthesiology·Shailendra JoshiEugene Ornstein
Mar 3, 2004·Mental Retardation and Developmental Disabilities Research Reviews·Mario C RattazziW Ted Brown
Feb 13, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Marie BlanchetteDavid Fortin
Jan 5, 2002·Expert Opinion on Investigational Drugs·S I Rapoport
Apr 7, 2007·Journal of Neurosurgical Anesthesiology·Shailendra JoshiJohn Pile-Spellman
Aug 12, 2018·Pharmaceutics·Zhi-Yuan ZhangGuo-Liang Zhang
Jun 3, 2021·Cancers·Fabrizio MarcucciAndrés J M Ferreri

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