Protein and synthetic polymer injection for induction of obstructive hydrocephalus in rats

Abstract

BackgroundThe objective of this study was to develop a simple and inexpensive animal model of induced obstructive hydrocephalus with minimal tissue inflammation, as an alternative to kaolin injection.MaterialsTwo-hundred and two male Sprague-Dawley rats aged 3 weeks received intracisternal injections of kaolin (25% suspension), Matrigel, type 1 collagen from rat tail, fibrin glue (Tisseel), n-butyl-cyanoacrylate (NBCA), or ethylene vinyl alcohol copolymer (Onyx-18 and Onyx-34). Magnetic resonance imaging was used to assess ventricle size. Animals were euthanized at 2, 5, 10 and 14 days post-injection for histological analysis.ResultsKaolin was associated with 10% mortality and successful induction of hydrocephalus in 97% of survivors (ventricle area proportion 0.168 ± 0.018). Rapidly hardening agents (fibrin glue, NBCA, vinyl polymer) had high mortality rates and low success rates in survivors. Only Matrigel had relatively low mortality (17%) and moderate success rate (20%). An inflammatory response with macrophages and some lymphocytes was associated with kaolin. There was negligible inflammation associated with Matrigel. A severe inflammatory response with giant cell formation was associated with ethylene vinyl alcohol copolymer.ConclusionKaolin predictably produces moderate to severe hydrocephalus with a mild chronic inflammatory reaction and fibrosis of the leptomeninges. Other synthetic polymers and biopolymers tested are unreliable and cause different types of inflammation.