Pre- and post-shunting observations in adult sheep with kaolin-induced hydrocephalus

Abstract

BackgroundThe objective of this study was to examine host-shunt interactions in sheep with kaolin-induced hydrocephalus.MethodsForty-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.ResultsIntraventricular 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.ConclusionsCerebrospinal 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.

Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

“…The possible cause of this difference may be due to the neglect of the hydrocephalic neonates by their mothers, neurogenic muscle atrophy, lethargy and general weakness of the hydrocephalic pups. Reduction in weight has been reported to be one of the first signs of development of hydrocephalus in experimental models (Del Bigio, 2001; López et al, 2003; McMullen et al, 2012; Johnston et al, 2013; Shaolin et al, 2015; Olopade et al, 2012). The body weight is an important index in developmental biology in neonatal pups and may be a pointer to an on-going pathologic condition.…”

Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone

“…The morphological analysis of Iba-1microglia cells suggested that microglial reactivity was mostly limited to the cellulose lamina tract. Additionally, hydrocephalus produced a thinning of the corpus callosum, but did not lead to an obvious loss of myelin staining as well as reactive astroglial changes in the white matter (Johnston et al, 2013). To evaluate the effects of hydrocephalus along the ventricular walls, we quantified the number of GFAP+ astrocytes lining the striatal wall of the ventricle.…”

A non-hydrocephalic goat experimental model to evaluate a ventriculosinus shunt

“…16 To facilitate the use of shunt systems that are similar in size and design to their human counterparts, a large animal model must be created. 17 A hydrocephalic sheep model to evaluate ventriculo-peritoneal shunts has been described in a previous study. 17 The purpose of this pilot study is to assess the suitability and feasibility of a goat model (specifically 'Saanen breed' goats, which are very similar to sheep) for evaluating the implantation technique and design of the ventriculosinus shunt.…”

“…17 A hydrocephalic sheep model to evaluate ventriculo-peritoneal shunts has been described in a previous study. 17 The purpose of this pilot study is to assess the suitability and feasibility of a goat model (specifically 'Saanen breed' goats, which are very similar to sheep) for evaluating the implantation technique and design of the ventriculosinus shunt. Since hydrocephalus is not required for addressing the research question, a nonhydrocephalic model was chosen.…”