Authors: Satish Krishnamurthy, MD, FAANS; Jie Li, MD; Haiya Hu, PhD (Manlius, NY)

Introduction: Pathogenesis of hydrocephalus is not clearly understood. Brain is permeable to water and we have shown that infusion of hyperosmolar dextrans into the ventricles is sufficient to cause hydrocephalus. Therefore, water influx into the ventricles is secondary to the presence of macromolecules in the ventricles. Macromolecules infused into the ventricles were distributed widely in the brain parenchyma especially in the perivascular region and cleared into the blood. There is delayed clearance in kaolin-induced hydrocephalus with stasis of the macromolecules in the perivascular region. Present study was undertaken to determine whether these changes are present in a genetic mouse model of hydrocephalus. Methods: POMGnT1 knockout (genes involved in protein glycosylation) mice results in congenital muscular dystrophy is associated with hydrocephalus. Ventricular volumes of the knockout mice (n=6) and wild type mice (n=5) were compared by calculations using histopathology sections utilizing ImageJ software. Next, 15µl of FITC 10KD dextran (FITCDex) was injected into brain lateral ventricle of knockout mice (n=3 at 30 and n=11 at 60 min) and wild type mice (n=3 at 30 and n=13 at 60 min). Histopathology was performed to determine if there was perivascular stasis. Results: Ventricular volume was larger (0.15 µl) in knockout mice as compared to the wild type mice (0.04 µl *P<0.05). (Graph 1 and Fig1). FITCDex particles were not distributed through the entire brain parenchyma at 30 mins in knockout like it was in the wild type mice. FITCDex particles clearance was delayed at 30 and 60 mins in the knockout mice as compared to wild type mice (Fig. 2 and Fig 3). Conclusion: Perivascular stasis suggestive of delayed clearance of macromolecules from the ventricles is a pathognomonic feature of hydrocephalus. Future studies of the impaired transport mechanism in this genetically mutated mouse might offer clues to finding a pharmacological cure of hydrocephalus.