Bumetanide increases postsynaptic inhibition after chronic SCI and decreases presynaptic inhibition with step‐training

Abstract

His research interest is to study the plasticity of the sensorimotor system, to uncover mechanisms and to implement therapies for individuals with sensory and/or motor dysfunction. His current work aims to use in vivo electrophysiology and pharmacological strategies in adult mammals to delineate mechanisms, underlying the regulation of the excitability of motoneurons and spinal networks after spinal cord injury or with amyotrophic lateral sclerosis.

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies

“…To restore the pre- and post-synaptic inhibition to mitigate spasticity, Caron et al investigated the effect of bumetanide, a sodium-potassium-chloride intrude (NKCC1) antagonist, to restore post-synaptic inhibition. While they did not combine bumetanide with rehabilitation as a long-term treatment, they found presynaptic inhibition was decreased only when bumetanide was acutely administered to step-trained animals; thus, bumetanide and training are potentially competing [ 85 ].…”

“…Maier et al claimed the reason why combinatorial treatment lacked collaborative effect is possibly due to an increase in pain perception [ 66 ]. Caron et al showed a competing effect of training with NKCC1 antagonists in the suppression of presynaptic inhibition [ 85 ]. If presynaptic inhibition decreases, pain-related behavior may increase due to the loss of suppression in the spinal circuit.…”

KCC2 Enhancers Normalize Reflex Responses and Improve Locomotor Function after Chronic Spinal Cord Injury

“…Increasing KCC2 activity restored alternation between the MG and TA muscles within each limb and reinstated inhibition to control the duration of muscle bursting, particularly in the TA muscle. Interestingly, these results (i.e., decreased co-contraction and burst duration) resemble those seen after successful body-weight supported step-training in both animal models (Barbeau & Rossignol, 1991) and in humans (Gorassini et al, 2009), suggesting that pharmacologically manipulating chloride homeostasis may reproduce some of the improvements associated with exercise-based rehabilitation (Bilchak et al, 2021a-b;Caron et al, 2023). Our results further suggest that by acting to restore endogenous inhibition solely in the central nervous system (Medina et al, 2014;Rivera et al, 1999), CLP290 may circumvent the muscle weakness and depression of motor output seen with current anti-spastic medications as burst amplitude during stepping remained unaffected by CLP290 administration.…”