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Journal of Neurology and Neurorehabilitation Research | Volume 3
August 23-24, 2018 | Paris, France
Neurology and Neurological Disorders
18
th
International Conference on
The role of Hypoxia in periventricular white matter degeneration
Santiago Martinez Sosa
UCL Institute of Neurology, UK
T
he deep and periventricular white matter is preferentially
affected in several neurological disorders, including cerebral
smallvesseldisease(SVD)andmultiplesclerosis(MS),suggesting
that common pathogenic mechanisms may be involved in this
injury. Here we consider the potential pathogenic role of tissue
hypoxia in lesion development, arising partly from the vascular
anatomy of the affectedwhitematter. Specifically, these regions
are supplied by a sparse vasculature fed by long, narrow end
arteries/arterioles that are vulnerable to oxygen desaturation
if perfusion is reduced (as in SVD, MS and diabetes) or if the
surrounding tissue is hypoxic (as in MS, at least). The oxygen
crisis is exacerbated by a local preponderance of veins, as
these can become highly desaturated ‘sinks’ for oxygen that
deplete it from surrounding tissues. Additional hemodynamic
deficiencies, including sluggish flow and impaired vasomotor
reactivity and vessel compliance, further exacerbate oxygen
insufficiency. The cells most vulnerable to hypoxic damage,
including oligodendrocytes, die first, resulting in demyelination.
Indeed, in preclinical models, demyelination is prevented if
adequate oxygenation is maintained by raising inspired oxygen
concentrations. In agreement with this interpretation, there is a
predilection of lesions for the anterior and occipital horns of the
lateral ventricles, namely regions located at arterial watersheds,
or border zones, known to be especially susceptible to
hypoperfusion and hypoxia. Finally, mitochondrial dysfunction
due to genetic causes, as occurs in leukodystrophies or due to
free radical damage, as occurs inMS, will compound any energy
insufficiency resulting from hypoxia. Viewing lesion formation
from the standpoint of tissue oxygenation not only reveals that
lesion distribution is partly predictable but may also informnew
therapeutic strategies.
Speaker Biography
Santiago Martinez Sosa is a medical student at University College London, from
where he also received his bachelor’s in Neuroscience (Hons). His interests include
hippocampal physiology, neuroinflammation, and neurodegenerative disease. He is the
UCL Medical Society coordinator for the Neurology society, which serves to facilitate
student involvement in all branches of the specialty. This is his first publication.
e:
zchamar@ucl.ac.uk