神经系统疾病

Restoring Motor functions in Spinal cord injury, Hemiplegic Cerebral Palsy, and Stroke by Botulinum toxin-induced Synaptic Competitive-Learning Therapy

Abstract

R Venkata Krishnan

Botulinum toxin (BoTx) is well known as a popular drug of choice for spasticity relief. Recent research shows that the toxin has synaptic competitive-learning (SCL) restoring plasticity properties acting at peripheral and central nervous sensory-motor centers. In the intact brain, SCL is naturally-endowed, that controls-regulates all learn-register-recallexecute (motor) functions, and memory storage functions during development and throughout adult life. In spinal cord injury (SCI), hemiplegic cerebral palsy (HCP), and stroke, there is partial/complete cessation of all SCL mechanisms in those injured and denervated centers. The denervated synaptic fields soon become reinnervated by spontaneous growths of aberrant, maladaptive synaptic weights. The massive loss of neurons in the injured site/s and the resultant synaptic weights (=defined as learned motor experiences stored as memory weights) distortions in the denervated centers cause spasticity and sensory-motor paralysis. It is known that BoTx spasticity relieving effects in single, isolated muscle/s are short-lived. However, clinical studies indicate that when given to multiple spastic muscles in serial/ repeats, BoTx generates significant recovery. Basic science studies show that BoTx generates neosynaptogenesis at motorendplates, on spinal motoneurons and motor cortex. It reinstalls the three cardinal courses of SCL viz. initial redundant connections, activity-dependent, competition-based pruning-selection refinement of connections at these sites. This paper presents i) a cognitive systems perspective of spasticity and motor paralysis, ii) a low-dose, multi-muscles BoTx treatment protocol designed to keep its paralyzing effects minimized, while prolong its SCL duration in order to initiate and consolidate long-lasting motor recovery in these disorders.