Platform for preclinical screening of neuroprotective strategies: a clinically relevant ICH model and standardized functional test battery

Introduction: Intracerebral hemorrhage (ICH) is among the most severe forms of stroke. Whereas traditional hemorrhagic stroke models reproduce hemorrhage within the striatum (specifically the putamen), localization of the hematoma with involvement of the internal capsule and globus pallidus may better recapitulate clinically relevant sensorimotor deficits due to more extensive basal ganglia involvement and damage to dense clusters of white matter tracts. Materials and Methods: Male CD1 mice (3–4 months, 30–35 g) were assigned to intact control (n=15) or ICH (n=15) groups. ICH was induced by stereotaxic injection of 30 μL autologous blood into the right cerebral hemisphere (2.3 mm lateral, 0.2 mm caudal to bregma, depths 3.0 and 3.5 mm). Neurological status was assessed using the modified Garcia scale, limb placement tests, horizontal and vertical pole tests, inverted grid test, corner test, and open field test at baseline and on days 1, 3, 7, 14, 21, and 28. Results and Discussion: The model showed high reproducibility with 33–40% acute mortality. All ICH mice developed contralateral sensorimotor-pyramidal deficits with predominant forelimb involvement. Garcia scores declined from 21 to 14.83±1.72 on day 1 with gradual but incomplete recovery by day 28 (18 [18;18.5]). Forelimb placement showed >50% acute deficit with a nonlinear recovery pattern, whereas hindlimb deficits appeared later (days 3–7) and persisted to day 21. The modified Garcia scale, forelimb placement, modified horizontal bar, and open field tests were most sensitive to functional impairment and recovery. Conclusion: Stereotaxic autologous blood injection into the basal ganglia (putamen and globus pallidus) with involvement of the internal capsule in mice reproduces clinically relevant, reproducible sensorimotor deficits with persistent functional impairment, making this model suitable for preclinical testing of neuroprotective strategies.