title: Pre- and post-shunting observations in adult sheep with kaolin-induced hydrocephalus.
abstract: BACKGROUND
  The objective of this study was to examine host-shunt interactions in sheep with kaolin-induced hydrocephalus.
  
  
  METHODS
  Forty-two sheep (29-40 kg) were utilized for this study. In 20 animals, various kaolin doses were injected into the cisterna magna including 10 and 50 mg/kg as well as 2-4 ml of a 25% kaolin suspension. Based on animal health and hydrocephalus development, 3 ml of a 25% kaolin suspension was chosen. In 16 animals, kaolin was administered and 6-8 days later, the animals received a custom made ventriculo-peritoneal shunt. In 8 animals ventricular CSF pressures were measured with a water manometer before kaolin administration and 7-8 days later. The sheep were allowed to survive for up to 9-12 weeks post-kaolin or until clinical status required euthanasia. Brains were assessed for morphological and histological changes. Ventricle/cerebrum cross sectional area ratios (V/C) were calculated from photographs of the sliced coronal planes immediately anterior to the interventricular foramina.
  
  
  RESULTS
  Intraventricular pressures increased from 12.4±1.1 cm H2O to 41.3±3.5 cm H2O following kaolin injection (p < 0.0001, n = 8). In all animals, we observed kaolin on the basal surface of the brain and mild (V/C 0.03-0.10) to moderate (V/C >0.10) ventricular expansion. The animals lost weight between kaolin administration and shunting (33.7±1.2 kg versus 31.0±1.7 kg) with weights after shunting remaining stable up to sacrifice (31.6±2.2 kg). Of 16 shunted animals, 5 did well and were sacrificed 9-12 weeks post-kaolin. In the remainder, the study was terminated at various times due to deteriorating health. Hydrocephalus was associated with thinning of the corpus callosum, but no obvious loss of myelin staining, along with reactive astroglial (glial fibrillary acidic immunoreactive) and microglial (Iba1 immunoreactive) changes in the white matter. Ventricular shunts revealed choroid plexus ingrowth in 5/16, brain tissue ingrowth in 1/16, problems with shunt insertion in 3/16, occlusion by hemorrhagic-inflammatory material in 5/16, or no obstruction in 2/16. Free flowing CSF indicated that the peritoneal catheter was patent.
  
  
  CONCLUSIONS
  Cerebrospinal fluid shunts in hydrocephalic sheep fail in ways that are reminiscent of human neurosurgical experience suggesting that this model may be helpful in the development of more effective shunt technology.
authors.affiliation: Brain Sciences, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
authors.forename: Miles G
authors.initials: MG
authors.lastname: Johnston
authors.affiliation: Department of Pathology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Del Bigio
authors.affiliation: Department of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Drake
authors.affiliation: Brain Sciences, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
authors.forename: Dianna
authors.initials: D
authors.lastname: Armstrong
authors.affiliation: Manitoba Institute of Child Health, Winnipeg, MB, Canada.
authors.forename: Domenico L
authors.initials: DL
authors.lastname: Di Curzio
authors.affiliation: Medtronic Neurosurgery, Goleta, CA, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Bertrand
keywords: Animal model; Hydrocephalus; Shunting