Chronic hydrocephalus and perihematomal tissue injury developed in a rat model of intracerebral hemorrhage with ventricular extension.

Abstract

Primary spontaneous intracerebral hemorrhage (ICH) with secondary intraventricular hemorrhage (IVH) is an important clinical problem of which little is known. IVH and hydrocephalus are independent predictors of poor outcome in ICH. The aims of this study were, therefore, to establish a rat model of ICH with ventricular extension and investigate the occurrence of post-hemorrhagic chronic hydrocephalus and perihematomal tissue injury. Based on our previous rat model of IVH, we adjusted the injection coordinates and 200μl autologous blood was stereotaxically infused into the right striatum (coordinates: 0.2mm posterior, 2.2mm lateral, and 5.0mm depth to the bregma). At 24h post-infusion, the rats produced reproducible hematoma and ventricle expansion, which closely mimics the ICH with ventricular extension in humans. Hematoma consequences and perihematomal tissue injury were evaluated on the acute phase. At 4weeks, ventricular dilatation, brain tissue loss, hippocampus volume, and cortical thickness were measured with magnetic resonance imaging and neurocognitive function was assessed using the Morris water maze test. With blood infusion, the animals demonstrated brain edema, blood-brain barrier breakdown, and marked perihematomal tissue injury on the acute phase. At 4weeks, the T2 images showed remarkable hydrocephalus and tissue loss, and the Morris water maze test revealed neurocognitive deficits. The present ICH with the ventricular extension rat model features characteristics of both ICH and IVH rat models, which could be used for extending our pathophysiological understanding of post-hemorrhagic chronic hydrocephalus and perihematomal tissue damage.