Research: Low oxygen levels and nerve damage

Alix JJP et al. Central axons preparing to myelinate are highly sensitivity to ischaemic injury. Annal Neurol. DOI: 10.1002/ana.23690 (epub)

Objective: Developing central white matter is subject to ischaemic-type injury during the period that precedes myelination. At this stage in maturation, central axons initiate a programme of radial expansion and ion channel re-distribution. Here we test the hypothesis that during radial expansion axons display heightened ischaemic sensitivity, when clusters of Ca2+ channels decorate future node of Ranvier sites.

Methods: Functionality and morphology of central axons and glia were examined during and after a period of modeled ischaemia. Pathological changes in axons undergoing radial expansion were probed using electrophysiological, quantitative ultrastructural and morphometric analysis in neonatal rodent optic nerve and peri-ventricular white matter axons studied under modeled ischaemia in vitro or after hypoxia-ischaemia in vivo.

Results: Acute ischaemic injury of central axons undergoing initial radial expansion was mediated by Ca2+ influx through Ca2+ channels expressed in axolemma clusters. This form of injury operated only in this axon population, which was more sensitive to injury than neighboring myelinated axons, smaller axons yet to initiate radial expansion, astrocytes or oligodendroglia. A pharmacological strategy designed to protect both small and large diameter pre-myelinated axons proved 100% protective against acute ischaemia studied under modeled ischaemia in vitro or after hypoxia-ischaemia in vivo.

Interpretation:Recent clinical data highlight the importance of axon pathology in developing white matter injury. The elevated susceptibility of early maturing axons to ischaemic injury described here may significantly contribute to selective white matter pathology and places these axons alongside pre-oligodendrocytes as a potential primary target of both injury and therapeutics. 
This data is based on studying cells in a test tube but suggests that in conditions of low oxygen (hypoxia) concentrations in a non-myelinated nervem is liable to damage. This indicates further that anti-oxidative molecules may have benefit saving nerves. This work is done in the context of a developing nerve rather than remyelination and so the same events may not occur once the nerve has been myelinated and demyelinated. However, there is a consistency of obervations to suggest this may be plausible that hypoxia may not be good for nerves…..just as as it is not good for any tissue to be hypoxic over the long-term and further points towards therapeutic targets to slow nerve damage.

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  • There has been some evidence of a benefit of antioxidant Alpha Lipoic Acid for MS but nothing concrete. Interestingly the Germns are doing a study of green tea extract and neuroprotection in progressive MS

  • @Iain

    Yes the Germans are doing a study. But they focus on something different. It is called EGCG (Epigallocatechin gallate) on of the main agents to be found in green tea.

  • Wouldn't the results of this study appear to be self-evident? I realize that the researchers are zeroing in on a specific cell type, and studying the precise mechanisms by which ischemic hypoxia does its damage to those cells, but wouldn't it be fair to say that hypoxia in general is not good for living things, be they complex organisms or individual cell types? And doesn't this beg the question, why are MS brains subject to such chronic hypoxia? We know that MS patients demonstrate hypoperfusion of blood through the CNS, which can result in hypoxia. Is this a result of the disease or part of the cause?

    Just a touch on the subject of antioxidants, recent research has found that the ingredients included in the nutritional supplement Protandim have a synergistic effect that increases the potency of the combined ingredients beyond that which might be expected by studying the individual components themselves. The ingredients of Protandim are green tea extract, ashwagandha, milk thistle, bacopa, and curcumin.

  • My MS has been stable and relapse-free for years, but I have noted an intolerance to long-distance flights, which I certainly didn't have before diagnosis. Anything over ten hours leaves me wiped out for a couple of days, but, worse, I then develop leg pain and sensory symptoms which can last for weeks. I also suffered one horrendous episode of jet-lag, which lasted five weeks. My physio has always attributed all this to hypoxia during the flight. Could she be right?

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