Ann Neurol. 2013 Aug 16. doi: 10.1002/ana.24006. [Epub ahead of print]
Neurological deficits caused by tissue hypoxia in neuroinflammatory disease.
Davies AL, Desai RA, Bloomfield PS, McIntosh PR, Chapple KJ, Linington C, Fairless R, Diem R, Kasti M, Murphy MP, Smith KJ.
Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London, WC1N 3BG.
To explore the presence and consequences of tissue hypoxia in experimental autoimmune encephalomyelitis ((EAE), an animal model of multiple sclerosis (MS)).
EAE was induced in Dark Agouti (DA) rats by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) and adjuvant. Tissue hypoxia was assessed in vivo using two independent methods: an immunohistochemical probe administered intravenously, and insertion of a physical, oxygen-sensitive probe into the spinal cord. Indirect markers of tissue hypoxia (e.g. expression of hypoxia-inducible factor-1α (HIF-1α), vessel diameter and number) were also assessed. The effects of brief (one hour) and continued (7 days) normobaric oxygen treatment on function were evaluated in conjunction with other treatments, namely administration of a mitochondrially-targeted antioxidant (MitoQ) and inhibition of inducible nitric oxide synthase (1400W).
Observed neurological deficits were quantitatively, temporally and spatially correlated with spinal white and grey matter hypoxia. The tissue expression of HIF-1α also correlated with loss of function. Spinal microvessels became enlarged during the hypoxic period, and their number increased at relapse. Notably, oxygen administration significantly restored function within one hour, with improvement persisting at least one week with continuous oxygen treatment. MitoQ and 1400W also caused a small but significant improvement.
We present chemical, physical, immunohistochemical and therapeutic evidence that functional deficits caused by neuroinflammation can arise from tissue hypoxia, consistent with an energy crisis in inflamed CNS tissue. The neurological deficit was closely correlated with spinal white and grey matter hypoxia. This realization may indicate new avenues for therapy of neuroinflammatory diseases such as MS. ANN NEUROL 2013. ©
Ok, it appears that neuroinflammation causes hypoxia, and that this hypoxia is correlated with observable neurological deficits, and that by restoring oxygen to normal, the neurological deficits get restored function.
So even if you had absolutely no venous obstructions, the inflammation present in MS would lead to hypoxia in the brain tissue during the time when the inflammation occurs. If you have venous obstructions and there was already underlying hypoxia, then that's a double whammy.
This provides a possible explanation for the immediate improvements sometimes seen after CCSVI angioplasty: when hypoxia is suddenly relieved, neurological deficits get restored function, sometimes within the hour as seen in the rats. This also provides evidence for the neurologists and/or Big Pharma to pursue treatment of hypoxia in MS. It's a long way from rats to humans but this is a start.