A cause and protective treatment for acute and progressive disability and grey matter atrophy

TY - JOUR

T1 - A cause and protective treatment for acute and progressive disability and grey matter atrophy

AU - Aguzzi, Erika A.

AU - Desai, Roshni A.

AU - Yang, Zhiyuan

AU - Davies, Andrew L.

AU - Mahad, Don

AU - Siow, Bernard

AU - Yenicelik, Ayse G.

AU - Desai, Radha

AU - Giama, Eleni

AU - Almasri, Al Beshr

AU - Colman, Miranda

AU - Geywitz, Celine

AU - Schirmer, Lucas

AU - Felts, Paul A.

AU - Smith, Kenneth J.

N1 - Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.

PY - 2026/4

Y1 - 2026/4

N2 - Acutely inflamed CNS lesions can be sufficiently hypoxic to cause temporary neurological disability. A new experimental lesion reveals that brief hypoxia can also ignite a slow-burning atrophy of the grey matter, resulting in a lifetime of slowly progressive disability. The progressive disability eventually exceeds that observed acutely, indicating that acutely functioning tissue can nevertheless be destined to atrophy. Remarkably, both the temporary initial disability and the ensuing progressive disability and atrophy are significantly reduced if the acute hypoxia is avoided by four days of treatment with vasodilating nimodipine, or by simply breathing raised oxygen concentration. Thus, a lifetime of progressive disability and neurodegeneration can be the legacy of a few days of inflammatory hypoxia experienced in young adulthood, and avoided by maintaining lesion oxygenation. The findings may help to understand and treat some progressive neurological disorders, including multiple sclerosis.

AB - Acutely inflamed CNS lesions can be sufficiently hypoxic to cause temporary neurological disability. A new experimental lesion reveals that brief hypoxia can also ignite a slow-burning atrophy of the grey matter, resulting in a lifetime of slowly progressive disability. The progressive disability eventually exceeds that observed acutely, indicating that acutely functioning tissue can nevertheless be destined to atrophy. Remarkably, both the temporary initial disability and the ensuing progressive disability and atrophy are significantly reduced if the acute hypoxia is avoided by four days of treatment with vasodilating nimodipine, or by simply breathing raised oxygen concentration. Thus, a lifetime of progressive disability and neurodegeneration can be the legacy of a few days of inflammatory hypoxia experienced in young adulthood, and avoided by maintaining lesion oxygenation. The findings may help to understand and treat some progressive neurological disorders, including multiple sclerosis.

KW - disease progression

KW - grey matter atrophy

KW - neurodegeneration

KW - neuroinflammation

KW - neuroprotection

KW - relapse

UR - https://www.scopus.com/pages/publications/105035242577

U2 - 10.1093/brain/awaf465

DO - 10.1093/brain/awaf465

M3 - Article

C2 - 41396858

AN - SCOPUS:105035242577

SN - 0006-8950

VL - 149

SP - 1144

EP - 1152

JO - Brain

JF - Brain

IS - 4

ER -