Background and Purpose: Most functional upper extremity motor recovery occurs in the first 4 weeks after ischemic stroke in humans and in the first week in rodent models. The majority of functional recovery in humans is spontaneous (i.e. occurs as a result of endogenous repair processes rather than rehabilitative interventions). In mouse models of stroke, recovery is impaired when post-stroke rehabilitation is delayed and there is very little spontaneous recovery. Cerebrolysin is a polypeptide preparation shown to enhance neuronal plasticity and to promote motor recovery in patients after stroke. In mice, we tested the hypothesis that Cerebrolysin can act early after stroke to enhance spontaneous motor recovery.
Methods: Adult C57Bl/6 mice were trained to perform a skilled prehension task to an asymptotic level of performance, after which they underwent photocoagulation-induced stroke in the caudal forelimb area (rodent primary motor cortex). The mice were then randomized to receive Cerebrolysin or saline injections beginning 24-hours post-stroke. Both groups were then retrained at the same prehension task by a blinded investigator. Stroke volumes were compared using immunohistochemistry.
Results: We have previously shown that training-associated recovery of prehension is complete if training is initiated after a 1-day delay but incomplete if training is initiated after a 7-day delay, even with additional training days. However, daily Cerebrolysin administration after stroke was associated with complete recovery of prehension by day 8, even in the absence of training. Stroke volumes were similar across all groups.
Conclusions: We conclude that Cerebrolysin administration during an early time window can lead to spontaneous recovery of motor function without a protective effect on stroke volume. This is one of the first demonstrations of spontaneous motor recovery in a rodent stroke model. Our mouse model, with all of the attendant genetic benefits, should allow us to determine at the cellular and molecular level how endogenous plasticity and medications like Cerebrolysin interact to mediate recovery.