Effect of hyperosmolar mannitol on convection-enhanced delivery into the rat brain stem

Introduction: 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 mul. 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 (V-d) 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.