Effect of hyperosmolar mannitol on convection-enhanced delivery into the rat brain stem.
BACKGROUND
Convection-enhanced delivery (CED) can safely achieve high local infusate concentrations within the rat brain stem with predictable distribution volumes. The authors investigated the effects of co-infusion or systemic administration of hyperosmolar mannitol on distribution parameters for infusions into the rat brain stem.


METHODS
Fifteen rats underwent stereotactic cannula placement into the pontine nucleus oralis (PnO) followed by infusions at a constant rate to a total volume of 1 microl. Five rats underwent infusion of fluorescein isothiocyanate (FITC)-dextran diluted in 20% mannitol. Five rats received an intraperitoneal injection of 20% mannitol 10 min prior to infusion of FITC-dextran diluted in isotonic saline. As a control group, 5 rats underwent infusion of FITC-dextran diluted in isotonic saline without mannitol administration. Serial brain sections were imaged using confocal microscopy with ultraviolet illumination, and distribution volume (Vd) was calculated by computer image analysis. Histologic analysis was performed on adjacent sections.


RESULTS
Volumes of distribution were not significantly increased by co-infusion of mannitol directly into the brain stem or by systemic mannitol administration compared to infusion without mannitol. Similarly, mannitol administration by either means failed to significantly alter maximal cross-sectional area or cranio-caudal extent of fluorescence. No animal demonstrated a postoperative neurological deficit or histologic evidence of tissue disruption.


CONCLUSIONS
Neither systemic administration nor co-infusion of hyperosmolar mannitol significantly affects distribution parameters for CED infusions into the rat brain stem.
Sandberg
David I
DI
Department of Neurosurgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Edgar
Mark A
MA
Souweidane
Mark M
MM
D000818:Animals; D001921:Brain / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D007552:Isotonic Solutions; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009994:Osmolar Concentration; D011149:Pons; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution; D014466:Ultraviolet Rays
D003911:Dextrans; D007552:Isotonic Solutions; C015219:fluorescein isothiocyanate dextran; D008353:Mannitol; D012965:Sodium Chloride; D016650:Fluorescein-5-isothiocyanate