Spinal cord injury: neurosurgical rewiring restores locomotor functions

Spinal cord injury: neurosurgical rewiring restores locomotor functions      

    

           At this point in time (2015) there are only limited numbers of treatment options for spinal cord injury (SCI) paralysis and they (e.g. stem cells; implanted stimulation devices) are all in clinical trials.  I present this neurosurgical treatment that is founded on over 40 years of basic sciences studies. This synaptic competitive-learning (SCL) therapy involves controlled neurapraxia surgery of limbs nerve trunks. I have experimentally proved (2001) in spinal cord complete injury (SCIc) animal model.    

         What is synaptic competitive-learning (SCL)?  In rats a SCIc from new born up to 20 days age does not result in paralysis. Body weight-support, standing, stepping all remain intact into adulthood. Beyond 20 days, SCIc always results in incapacitating complete paralysis. I found (1991) that the function preservation seen in the young rats is due to restorative SCL rewiring within the isolated cord and the limb muscles. At older ages this rewiring capability is lost.  Now the question is: can such rewiring be done in SCI in adult?  

          Briefly, SCL is a naturally-endowed, post-birth connectivity phenomenon in the intact spinal cord, during locomotor learning (crawl, sit, stand, step, and walk) and maturation. At birth, each muscle fibre is innervated by more than three, four motor terminals derived from different motoneurons. Then, as locomotor learning continues motor activity-dependent,  competition takes place between the motor terminals to gain control of that muscle fibre. Functionally fitting terminal is retained and stabilized while other terminals are pruned. Eventually each muscle fibre is controlled by a single motor terminal.  Stretch and reciprocal inhibitory reflexes mature and reach their adult activity pattern. And by late infancy these SCL wirings in the limb muscles and spinal cord circuitry get completed and locomotor maturation (in rats 20 days age) is reached. This post-birth (epigenetic), activity-dependent, competition-based synaptic connectivity phenomenon (Krishnan, 2013 Open access) gives the brain-spinal cord unlimited (motor) learning and memory-storing capability throughout life as opposed to the pre-birth, genetically pre-determined, rather restricted connectivity processes.     

            I designed a simple neurosurgical procedure (Krishnan, 1991; 2001) in the adult SCIc animal model that would simulate and reinstall each of the stages of the SCL mechanisms in the injured cord circuitry and the limb muscles. This involves controlled neurapraxia (nerve crush) of the paralyzed limbs motor nerve trunks (sciatic, femoral, and obturator) so as to interrupt impulse conduction in about 20-30 percent of the sensory-motor axons. All the limb muscles become temporarily partially denervated. Then, spontaneous sprouting of intact motor axons follows within these muscles. When the interrupted motor axons regenerate and arrive (in the animal model six to eight weeks post-neurapraxia) into their muscles synapse competition takes place between the sprouted and the regenerated motor terminals to gain control of the denervated muscle fibres. This competition is motor activity-dependent. Functionally appropriate connections are selected and stabilized while others are pruned. In the meantime, the motoneurons soma sizes become plastic and are resized. A similar synapse competition-selection takes place on their soma-dendritic surfaces. The excitatory-inhibitory (E-I) connections weights impinging on the motoneurons undergo corrective repositioning and the E-I balance between synergists-antagonists muscles is restored.  6-10 weeks following the SCL therapy swimming and stepping commenced in these animals sustained for several months (see videos).    https://www.youtube.com/results?search_query=krishnanspinal

 

          How do we know for certain that it is indeed the SCL therapy that brought the motor restoration, and not due to regeneration across the injury site?  First, none of the untreated control animals showed recovery; they remained paralyzed and indeed developed extensor-adductors spasticity and “scissoring” of the limbs.  Second, in all the neurapraxia animals spasticity was absent. Instead they regained the normal flexion position of the limbs. Third, the treated animals recovered swimming and ground progression that persisted for several months of post-operative survival. Related study (Blesch, 2012) in rats shows that a conditioning lesion (neurapraxia) of the sciatic nerve trunk six weeks, or even eighteen months after a cervical SCI induces intra-spinal, long-range regeneration of sensory axons that continued for several months by the re-expression of a wide array of growth promoting genes.

          How does neurapraxia treatment prevent spasticity?  Selective neurectomy is a well-known neurosurgical procedure for relief of intractable spasticity. This consists of permanent, partial surgical denervation (hyponeurotization) of spastic muscle/s. In controlled neurapraxia the synapse competition and the resizing of motoneurons soma reduces/abolishes spasticity. Computational modelling shows that the synapse competition and the resizing of soma sizes enable the motoneurons to selectively eliminate topographically incorrect synapses and self-correct errors in their firing properties.

        What is Neurorehabilitation? Present rehabilitation programs e.g. Body weight-supported treadmill walking is incorrectly called neurorehabilitation. Indeed they are rather desperate, arduous retraining of the injured cord circuitry that is stubbornly learning-resistant. Whereas SCL therapy rewires neuromuscular and cord circuitry. Spasticity is abolished and neuro relearning commences. In this intrinsically generated locomotor performance all muscles of the limbs participate.  When this relearning is combined with retraining then it becomes true neurorehabilitation.    Our research (2009; 2013) shows that in human SCI, Botulinum toxin (BoTx) when administered in small doses to select muscles in serial sessions can replay and reinstall SCL precisely similar to neurapraxia.  Researchers might question why I chose an amphibian model. I did these experiments at my retirement some years ago in the total absence of funding and technical assistance. I invite neurosurgeons/neurologists to study the two SCL treatment options: surgical/BoTx-induced, debate and translate.    

                 

 

Venkata Krishnan R                           

Krish_venk@yahoo.com                                                     

 

Venkata Krishnan R (2013) Restoring Motor functions in Spinal cord injury, Hemiplegic Cerebral Palsy, and Stroke by Botulinum toxin-induced Synaptic Competitive-Learning  Therapy. J Neurol Disord 1: 134. doi:10.4172/2329- 6895.1000134

 

 

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