Characterization of the brain injury, neurobehavioral profiles, and histopathology in a rat model of cerebellar hemorrhage

Spontaneous cerebellar hemorrhage (SCH) represents approximately 10% of all intracerebral hemorrhage (ICH) and is an important clinical problem of which little is known. This study stereotaxically infused collagenase (type VII) into the deep cerebellar paramedian white matter, which corresponds to the most common clinical injury region. Measures of hemostasis (brain water, hemoglobin assay, Evans blue, collagen-IV, ZO-1, and MMP-2 and MMP-9) and neurodeficit were quantified 24 hours later (Experiment 1). Long-term functional outcomes were measured over 30 days using the ataxia scale (modified Luciani), open field, wire suspension, beam balance, and inclined plane (Experiment 2). Neurocognitive ability was assessed on the third week using the rotarod (motor learning), T maze (working memory), and water maze (spatial learning and memory) (Experiment 3), followed by a histopathological analysis 1 week later (Experiment 4). Stereotaxic collagenase infusion caused dose-dependent elevations in brain edema, neurodeficit, hematoma volume, and blood-brain barrier rupture, while physiological variables remained stable. Most functional outcomes normalized by the third week, while neurocognitive testing showed deficits parallel to the cystic-cavitary lesion at 30 days. All animals survived until sacrifice, and obstructive hydrocephalus did not develop. These results suggest that the model can generate important translational information about this subtype of ICH and could be used for future investigations of therapeutic mechanisms after cerebellar hemorrhage.

Research highlights► Spontaneous cerebellar hemorrhage (SCH) is an important clinical problem. ► This study establishes a new animal model for experimental use in rats. ► Early hemostatic mechanisms paralleled that which is known clinically. ► Long-term neurobehavioral and histopathological evaluations were conducted. ► This instructive model supports experimental studies of cerebellar hemorrhage.