Saturday, 15 February 2014

Uncontrolled nerve regrowth after injury can contribute not solve the problem

Beauparlant J, van den Brand R, Barraud Q, Friedli L, Musienko P, Dietz V, Courtine G. Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury. Brain. 2013;136(Pt 11):3347-61.


Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal (behind) to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral (lower back) circuitries in adult rats with a staggered thoracic hemisection (half the spinal cord is severed) injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency (slow) reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific (the spinal cord has layers of nerves each layer is given a name lamina I to X) remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution.

Stem cells are the answers to many peoples hopes for repair in MS. Although remyelination may be part of the process, repair of damaged nerve circuitry is the Holy Grail.


However, whilst nerves in the periphery can regrow generally the nerves in the central nervous system are stopped from doing this. The question is why and the answer is there must be some advantage to doing this. So our hopes for stem cells fly in the face of nature.


Although stem cells and nerve regrowth are part of MS research, this has been the focus in spinal cord injury research for along time. This can teach us a lot. Furthermore the problem in spinal cord injury is less challenging as you do not have to deal with the ongoing disease process that drives the process forward as occurs in MS. So watching to see how success in this area is coming along will be a good gauge of where MS nerve repair could be.

The nervous system is the information superhighway of the body and damage to it can stop of slow movement of this information However, just like the internet if there is damage to one pathway the internet has the option to use other pathways to get the same information to you. This is done in nano and milliseconds and if it goes down the wrong pathway it can regroup and go down another at no cost except a bit of lost time. However, the human body is less resilient yet it can learn to adapt and can form new connectivity pathways and this is called Nervous plasticity

If it works, you regain lost abilities, but if you get it wrong then may be pain is coming your way so the consequences of choosing the wrong pathway is more of a problem than using the internet. 


In this study after the injury the nervous system in the spine remodelled itself to try and make new connections and without any guidance cues, when the dots (nervous connections) were joined up (in the wrong way) then it caused more problems. So misguided regrow of nerves can be a bad thing and so it will be important to understand how cues to desired nerve growth patterns occur. Stem cell replacement is not a simple task of injecting cells and hoping for the best. They have to get into the right place they have to survive and they have to change into the desired cell type and then make the desired connections and then the brain has to adapt.





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