Increased CSF osmolarity reversibly induces hydrocephalus in the normal rat brain

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.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.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.Hydrocephalus is a CNS disorder characterized by the abnormal accumulation of cerebrospinal fluid (CSF) in cerebral ventricles and increased ventricle volume (VV). The pathogenesis underlying the emergence of hydrocephalus is poorly understood [1-5] and remains an unresolved issue despite many years of investigation [6-10]. Clinical hydrocephalus is commonly classified based on symptomatology as either obstructive hydrocephalus, communicating hydrocephalus, or normal pressure hydrocephalus (NPH). Classically, hydrocephalus is thought to reflect either a blockage of CSF circulation within the ventricles and/or impaired CSF absorption through the arachnoid projections into the cranial venous sinuse