Evaluation of the hematoma consequences, neurobehavioral profiles, and histopathology in a rat model of pontine hemorrhage.

OBJECT: Primary pontine hemorrhage (PPH) represents approximately 7% of all intracerebral hemorrhages (ICHs) and is a clinical condition of which little is known. The aim of this study was to characterize the early brain injury, neurobehavioral outcome, and long-term histopathology in a novel preclinical rat model of PPH.

METHODS

The authors stereotactically infused collagenase (Type VII) into the ventral pontine tegmentum of the rats, in accordance with the most commonly affected clinical region. Measures of cerebrovascular permeability (brain water content, hemoglobin assay, Evans blue, collagen Type IV, ZO-1, and MMP-2 and MMP-9) and neurological deficit were quantified at 24 hours postinfusion (Experiment 1). Functional outcome was measured over a 30-day period using a vertebrobasilar scale (the modified Voetsch score), open field, wire suspension, beam balance, and inclined-plane tests (Experiment 2). Neurocognitive ability was determined at Week 3 using the rotarod (motor learning), T-maze (working memory), and water maze (spatial learning and memory) (Experiment 3), followed by histopathological analysis 1 week later (Experiment 4).

RESULTS

Stereotactic collagenase infusion caused dose-dependent elevations in hematoma volume, brain edema, neurological deficit, and blood-brain barrier rupture, while physiological variables remained stable. Functional outcomes mostly normalized by Week 3, whereas neurocognitive deficits paralleled the cystic cavitary lesion at 30 days. Obstructive hydrocephalus did not develop despite a clinically relevant 30-day mortality rate (approximately 54%).

CONCLUSIONS

These results suggest that the model can mimic several translational aspects of pontine hemorrhage in humans and can be used in the evaluation of potential preclinical therapeutic interventions.