title: Intracarotid infusion of hypertonic mannitol changes permeability of blood-brain barrier to methotrexate in rats.
abstract: OBJECTIVE
  To study whether infusion of hypertonic mannitol through internal carotid artery could enhance methotrexate (MTX) concentration in rat cortex and to study the time-course of this process.
  
  
  METHODS
  Hypertonic mannitol was infused into the rat left internal carotid artery, ten minutes later, MTX was injected from the left femoral vein (i.v.) or left common carotid artery (ia), and the concentration of MTX was assayed 1 h later. Rats were given MTX at different time interval after infusion of mannitol, and the concentration of MTX was assayed 1 h after drug administration. At the same time, the rat cortex's density was analyzed.
  
  
  RESULTS
  After mannitol infusion, MTX's concentration in rat cortex increased 2.54 times (i.v.) and 3.41 times (ia) as compared to control, respectively. After 10 min, such effect reached its peak, and almost disappeared after 6 h. There was no significant change in rat cortex's density.
  
  
  CONCLUSIONS
  Mannitol can make blood-brain barrier (BBB) reversibly permeable, and increase MTX concentration in brain without any obvious injury to the brain.
authors.affiliation: Center of Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. panguoyu@hotmail.com
authors.forename: G Y
authors.initials: GY
authors.lastname: Pan
authors.forename: X D
authors.initials: XD
authors.lastname: Liu
authors.forename: G Q
authors.initials: GQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002343:Carotid Artery, Internal; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D006982:Hypertonic Solutions; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D008353:Mannitol / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006982:Hypertonic Solutions; D008353:Mannitol; D008727:Methotrexate