Introduction: Hydrocephalus can be experimentally induced by producing a sustained increase in CSF osmolarity. This implies that macromolecular content in the CSF is critical in determining the water content. We have previously shown that intraventricularly injected dextran is rapidly concentrated in the perivascular space surrounding microvessels throughout the brain. To explore how the brain clears the macromolecules in CSF for maintaining its osmotic gradient, we investigated the kinetics of the clearance of fluorescently-labeled 10KD dextran from CSF in the normal rat brain.
Methods: Sprague-Dawley rats were randomly divided into two groups. Then rats received one time CSF injection through cisterna magna with either FITC-labeled 10KD dextran solution (1µg/µl) in group I (n=7) or sterile saline in group II (n=7). Blood and urine samples were collected prior to injection, at 30 mins and at 60 mins after injection. Both serum and urine samples were examined by spectrophotometric analysis for tracing the FITC-labeled 10KD dextran particles.
Results: Nonparametric tests (Wilcoxon two sample tests and signed rank tests) were done. The p-value for the comparisons of treated vs control is 0.046 for both urine and serum at both 30 and 60 minutes. For comparisons within the treated group, the p-value for pre vs 30 and 60 is 0.015 for both urine and serum. For urine, 30 vs 60 the p-value was 0.031. For serum, 30 vs 60 the p-value was 0.234.
Conclusions: Intraventricular dextran is cleared rapidly through blood brain barrier in normal rat to maintain its normal osmotic gradient. Dysregulation of CSF osmolarity resulting from a sustained influx of macromolecules in to CSF and/or compromise of clearance mechanisms may be the underlying cause of hydrocephalus. These processes may offer novel therapeutic targets for the treatment of clinical hydrocephalus.
Patient Care: This research will help identify targets for pharmacological treatment of hydrocephalus which is currently treated only by surgical means.
Learning Objectives: By the conclusion of the session, participants should be able to 1) describe the role of osmolar gradients in hydrocephalus 2) understand how macromolecules are cleared from the ventricles
References: Krishnamurthy S, Li J, Schultz L, Jenrow KA: Increased CSF osmolarity reversibly induces hydrocephalus in the normal rat brain. Fluids and Barriers of the CNS. July 11;9(1):13, 2012.
10. Krishnamurthy S, Li J, Schultz L, McAllister JPII: Intraventricular infusion of hyperosmolar dextran induces hydrocephalus: a novel animal model of hydrocephalus. Cerebrospinal Fluid Research December 2009 6(1):16.