Abstract TP253: Early Intense Rehabilitation Does Not Reduce Impairment After Intra-striatal Hemorrhagic Stroke In Rats

Abstract

Intracerebral hemorrhage (ICH) causes rapid mechanical damage and initiates secondary injury mechanisms, such as from toxic by-products of blood degradation, that cause extended cell death. Experimentally, several rehabilitative treatments (rehab) can mitigate late cell death, and one recent study suggests it is by accelerating hematoma clearance, thereby minimizing neurotoxicity. Here, we assessed whether early, intense, enriched rehab (ER) enhances functional benefit and reduces ICH injury. Methods: In experiment 1, rats (n=56) were randomly assigned to groups following collagenase-induced striatal ICH: ER-Dark, ER-Light, CONTROL-Dark, or CONTROL-Light. ER rats completed four reach training sessions and six hours of environmental enrichment daily for 10d (d5-14 after ICH), in either the dark or light phase of their housing cycle. Rats were euthanized on d14 and hematoma volume was assessed. In experiment 2 (n=72), rats were randomized to: ER-10, ER-20, or CONTROL. Using the same ER protocol, rats in ER-10 and ER-20 completed 10d (d5-14) or 20d (d5-14 and 19-28) of ER during the dark phase of their housing cycle. Rats were euthanized on d60, and brains were fixed for histological processing. In both experiments, rats completed behavioural assessments prior to ICH, pre-treatment (d4 post-ICH) and post treatment (experiment 1, d13-14; experiment 2, d16-17 and d30-31). Results: In experiment 1 there was no significant difference in reaching intensity between ER completed in light vs. dark (p=0.3318), and both groups reached extensively (3912±947 reaches). ER resulted in slightly better reaching success between d4 and d14 (p=0.0272) but did not significantly alter residual hematoma volume (p=0.9653). In experiment 2, ER duration did not significantly impact reaching success between d4 and d31 (p=0.0587) or reduce lesion size (p=0.6401). Conclusion: While similar rehab methods have been beneficial in other work, these findings suggest that slight variations in protocols (rehab initiation, intensity, time in enrichment) have a large impact on treatment efficacy. Additionally, these results underscore the importance of studying rehabilitation after ICH, as the use of comparable treatments appear to be far more efficacious for ischemic injury.