Acute baclofen administration promotes functional recovery after spinal cord injury

Abstract

Background context: Traumatic spinal cord injury (SCI) leads to severe motor and sensory functional impairments that affect personal and social behaviors. Medical advancements have improved supportive therapeutic measures for SCI patients, but no effective neuroregenerative therapeutic options exist to date. Deficits in motor function are the most visible consequence of SCI. However, other complications, as spasticity, produce a significant impact on SCI patient's welfare. Baclofen, a GABA agonist, is the most effective drug for spasticity treatment. Interestingly, emerging data reveals that baclofen can also play a role on neuroprotection and regeneration after SCI.

Purpose: The goal of this study was to understand the potential of baclofen as a treatment to promote recovery after SCI.

Study design: We used a pre-clinical SCI mouse model with the administration of baclofen 1 mg/Kg at different time-points after injury.

Methods: Behavior analysis (locomotor and bladder function) were performed during nine weeks of the in vivo experiment. Afterwards, spinal cords were collected and processed for histological and molecular analysis.

Results: Our data showed that baclofen leads to locomotor improvements in mice when its administered acutely after SCI. Moreover, baclofen administration also led to improved bladder function control in all experimental groups. Interestingly, acute baclofen administration modulates microglia activation state and levels of circulating chemokines and cytokines, suggesting a putative role of baclofen in the modulation of the immune response.

Conclusions: Although further studies must be performed to understand the mechanisms that underlie the functional improvements produced by baclofen, our data shed light into the pharmacological potential of baclofen to promote recovery after SCI.

Clinical relevance: Our outcomes revealed that baclofen, a well-known drug used for spasticity management, improves the motor performance after SCI in a pre-clinical animal model. Our data opens new avenues for pharmacological strategies design to promote SCI recovery.

Keywords: Baclofen; Functional recovery; GABAergic drugs; Immune response modulation; Neuroinflammation; Spinal Cord Injury.