Cerebrospinal Fluid from Aneurysmal Subarachnoid Hemorrhage Patients Leads to Hydrocephalus in Nude Mice

Our prior studies have found that intracerebroventricular injection of blood components can cause hydrocephalus and choroid plexus epiplexus cell activation in rats. To minimize the cross-species reaction, the current study examines whether intraventricular injection of acellular components of cerebrospinal fluid (CSF) from subarachnoid hemorrhage patients can cause hydrocephalus and epiplexus macrophage activation in nude mice which lack a T cell inflammatory response. Adult male nude mice received intraventricular injections of acellular CSF from subarachnoid hemorrhage patients or a control patient. All mice had preoperative magnetic resonance imaging as baseline and postoperative scans at 24 h after CSF injection to determine ventricular volume. Brains were harvested at 24 h for brain histology, immunohistochemistry, and electron microscopy. Intraventricular injection of CSF from two of five subarachnoid hemorrhage patients obtained < 48 h from ictus resulted in ventricular enlargement at 24 h. CSF-related hydrocephalus was associated with activation of epiplexus macrophages and ependymal injury. Components of the acellular CSF of subarachnoid hemorrhage patients can cause epiplexus macrophage activation, ependymal cell damage, and ventricular enlargement in nude mice. This may serve as a unique model to study mechanisms of hydrocephalus development following subarachnoid hemorrhage.