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

Two-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.Kaolin 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.Kaolin 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.Hydrocephalus is a common neurological condition characterized by enlargement of the cerebrospinal fluid (CSF)-filled ventricles, which leads to damage of surrounding brain tissue [1,2]. To study the pathogenesis of brain damage, hydrocephalus can be experimentally induced through a variety of techniques [3]. The most widely used method is through the injection of kaolin (aluminum silicate) into the cisterna magna [4]. This method is inexpensive, simple, reliable, minimally invasive leaving no visible wound, and to some extent titratable. Kaolin causes an inflammatory response of the leptomeninges and the subarachnoid space around the brainstem and cerebellum, thus causing obstruction at the fourth ventricle outl