Acute administration of Baclofen after spinal cord injury improves
locomotor behavior, bladder control and modulates the inflammatory
response.
Abstract
Spinal cord injury (SCI) leads to severe motor and sensory functional
impairments that affect personal and social behaviors. With no effective
treatment, deficits in motor function are the most visible consequence
of SCI. However, other complications produce a significant impact on SCI
patient’s welfare. Spasticity is a neurological impairment that affects
the control of muscle tone as a consequence of an insult in the central
nervous system (e.g., SCI). Baclofen, a GABA agonist, is the most
effective drug for spasticity treatment. This drug activates GABAB
receptors decreasing the neurotransmitters release and neuronal
hyperpolarization, which results in spasticity relief. Interestingly,
emerging data reveals that Baclofen can also play a role on
neuroprotection and regeneration after SCI. Our goal is to highlight the
role of Baclofen as a potential treatment to promote recovery from SCI.
We used a compression SCI mouse model with the administration of
Baclofen at different time-points after injury. Our data showed that
Baclofen is more effective when a single dose is administered acutely,
leading to locomotor improvements in mice. 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
cytokines, suggesting a role of Baclofen in the modulation of the immune
response. Although deeper studies must be performed to understand the
cellular/molecular mechanisms that underlie the functional improvements
produced by Baclofen, our data shed light into the pharmacological
potential of Baclofen to promote recovery in a SCI context.