Communicating hydrocephalus in adult rats with kaolin obstruction of the basal cisterns or the cortical subarachnoid space

Communicating hydrocephalus (CH) occurs frequently, but clinically-relevant animal models amenable to diagnostic imaging and cerebrospinal fluid shunting are not available. In order to develop and characterize models of subarachnoid space (SAS) obstruction at the basal cisterns (BC) or cerebral convexities (CX), 25% kaolin was injected in adult female Sprague-Dawley rats following halothane anesthesia; intact- or saline-injected animals served as controls. For BC animals (n=28 hydrocephalics, n=20 controls), an anterior approach to the Cl-clivus interval was employed and 30 VI of kaolin or saline was injected. For CX injections (n=13 hydrocephalics, n=3 controls), 50-60 mu l of kaolin was injected bilaterally after separating the partitions in the SAS. In BC-injected rats, kaolin was observed grossly in the basal cisterns but not in the cisterna magna or at the foramina of Luschka, indicating that communicating (or extra-ventricular) - not obstructive - hydrocephalus had been induced. Following ketamine/xylazine anesthesia, magnetic resonance imaging (MRI) of gadolinium injected into the lateral ventricle also demonstrated CSF flow from the foramina of Luschka. MRI also revealed that ventriculomegaly progressed steadily in BC animals and by 2 weeks post-kaolin the mean Evan's ratio (frontal horn) increased significantly (mean 0.45 compared to 0.31 in intact- and 0.34 in saline-injected controls; p < 0.001 for each). CX animals exhibited kaolin deposits covering approximately 80% of the cerebral hemispheres and developed noticeable ventriculomegaly (mean Evan's ratio 0.40), which was significant relative to intact animals (p = 0.011) but not saline-injected controls. Surprisingly, ventriculomegaly following CX injections was less severe and much more protracted, requiring 3-4 months to develop compared to ventriculomegaly produced by BC obstruction. No hydrocephalic animals demonstrated obvious neurological deficits, but BC-injected animals that subsequently developed more severe ventriculomegaly exhibited nasal discharges and coughing for several days following kaolin injection. The new BC model is relevant because the clinical presentation of CH in children is often associated with obstruction at this site, while the CX model may be more representative of late adult onset normal pressure hydrocephalus. (c) 2008 Elsevier Inc. All rights reserved.