A Novel Model of Acquired Hydrocephalus for Evaluation of Neurosurgical Treatments
Abstract Background.Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in ways similar to gyrencephalic species and whose size is not amenable to evaluation of clinically-relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs. Methods. Acquired hydrocephalus was induced in 30-35-day old pigs by percutaneous intracisternal injections of kaolin. Intracisternal and intraventricular injections of autologous blood was attempted in 2 cases to induce post-hemorrhagic hydrocephalus. Magnetic resonance imaging (MRI) was employed to evaluate the progression of ventriculomegaly and plan the surgical implantation of ventriculoperitoneal shunts at approximately 1–4 weeks post-kaolin. Behavioral and neurological status was assessed continuously. Results. Bilateral ventriculomegaly occurred post-induction and was characterized by enlargement of all portions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in basal cisterns but the cisterna magna was patent. In 14 untreated hydrocephalic animals, mean total ventricular volumes were 6786 ± 4336 SD mm3 at 17–57 days post-kaolin, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 in sham controls. Consistent with human hydrocephalus, intermittent disruption of the ventricular zone of the lateral ventricles was characterized by loss of multiciliated ependymal cells and the appearance of reactive astrocytes. Past the post-induction recovery period, untreated pigs were asymptomatic in spite of exhibiting mild-moderate ventriculomegaly. Shunted animals developed ataxia and lethargy only when obstruction of the ventricular catheter and/or distal valve occurred. Conclusions. Mechanical induction of acquired hydrocephalus produces a reliable in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.