Role of the BDNF-TrkB pathway in KCC2 regulation and rehabilitation following neuronal injury: A mini review

In most mature neurons, low levels of intracellular Cl− concentrations ([Cl−]i) are maintained by channels and transporters, particularly the K+-Cl- cotransporter 2 (KCC2), which is the only Cl− extruder in most neurons. Recent studies have implicated KCC2 expression in the molecular mechanisms underlying neuronal disorders, such as spasticity, epilepsy and neuropathic pain. Alterations in KCC2 expression have been associated with brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB). The present review summarizes recent progress regarding the roles of Cl− regulators in immature and mature neurons. Moreover, we focus on the role of KCC2 regulation via the BDNF-TrkB pathway in spinal cord injury and rehabilitation, as prior studies have shown that the BDNF-TrkB pathway can affect both the pathological development and functional amelioration of spinal cord injuries. Evidence suggests that rehabilitation using active exercise and mechanical stimulation can attenuate spasticity and neuropathic pain in animal models, likely due to the upregulation of KCC2 expression via the BDNF-TrkB pathway. Moreover, research suggests that such rehabilitation efforts may recover KCC2 expression without the use of exogenous BDNF. •Exercise and mechanical stimulation are beneficial in spasticity and neuropathic pain.•KCC2 expression is regulated via translational and post-translational mechanisms.•Rehabilitation efforts may recover KCC2 expression without exogenous BDNF.