Increased CSF osmolarity reversibly induces hydrocephalus in the normal rat brain

BACKGROUND: Hydrocephalus is a central nervous system (CNS) disorder characterized by the abnormal accumulation of cerebrospinal fluid (CSF) in cerebral ventricles, resulting in their dilatation and associated brain tissue injury. The pathogenesis of hydrocephalus remains unclear; however, recent reports suggest the possible involvement of abnormal osmotic gradients. Here we explore the kinetics associated with manipulating CSF osmolarity on ventricle volume (VV) in the normal rat brain. METHODS: CSF was made hyper-osmotic by introducing 10KD dextran into the lateral ventricle, either by acute injection at different concentrations or by chronic infusion at a single concentration. The induction and withdrawal kinetics of dextran infusion on VV were explored in both contexts. RESULTS: Acute intraventricular injection of dextran caused a rapid increase in VV which completely reversed within 24 hours. These kinetics are seemingly independent of CSF osmolarity across a range spanning an order of magnitude; however, the magnitude of the transient increase in VV was proportional to CSF osmolarity. By contrast, continuous intraventricular infusion of dextran at a relatively low concentration caused a more gradual increase in VV which was very slow to reverse when infusion was suspended after five days. CONCLUSION: We conclude that hyperosmolar CSF is sufficient to produce a proportional degree of hydrocephalus in the normal rat brain, and that this phenomenon exhibits hysteresis if CSF hyperosmolarity is persistent. Thus pathologically-induced increases in CSF osmolarity may be similarly associated with certain forms of clinical hydrocephalus. An improved understanding of this phenomenon and its kinetics may facilitate the development of novel therapies for the treatment of clinical hydrocephalus.