Prelude to the special issue on novel neurocircuit, cellular and molecular targets for developing functional rehabilitation therapies of neurotrauma.

Abstract The poor endogenous recovery capacity and other impediments to reinstating sensorimotor or autonomic function after adult neurotrauma have perplexed modern neuroscientists, bioengineers, and physicians for over a century. However, despite limited improvement in options to mitigate acute pathophysiological sequalae, the past 20 years have witnessed marked progresses in developing efficacious rehabilitation strategies for chronic spinal cord and brain injuries. The achievement is mainly attributable to research advancements in elucidating neuroplastic mechanisms for the potential to enhance clinical prognosis. Innovative cross-disciplinary studies have established novel therapeutic targets, theoretical frameworks, and regiments to attain treatment efficacy. This Special Issue contained eight papers that described experimental and human data along with literature reviews regarding the essential roles of the conventionally undervalued factors in neural repair: inflammatory milieu, neural-respiratory inflammasome axis, modulation of glutamatergic and monoaminergic neurotransmission, neurogenesis, nerve transfer, recovery neurobiology components, and the spinal cord learning, respiration and central pattern generator neurocircuits. The focus of this work was on how to induce functional recovery from manipulating these underpinnings through their interactions with secondary injury events, peripheral and supraspinal inputs, neuromusculoskeletal network, and interventions (i.e., activity training, pharmacological adjuncts, electrical stimulation, and multimodal neuromechanical, brain-computer interface [BCI] and robotic assistance [RA] devices). The evidence suggested that if key neurocircuits are therapeutically reactivated, rebuilt, and/or modulated under proper sensory feedback, neurological function (e.g., cognition, respiration, limb movement, locomotion, etc.) will likely be reanimated after neurotrauma. The efficacy can be optimized by individualizing multimodal rehabilitation treatments via BCI/RA-integrated drug administration and neuromechanical protheses.