Vasodilator dysfunction and oligodendrocyte dysmaturation in aging white matter

Zsolt Bagi, Dieter D. Brandner, Phuong Le, David W. McNeal, Xi Gong, Huijuan Dou, David J. Fulton, Allison Beller, Thuan Ngyuen, Eric B. Larson, Thomas J. Montine, C. Dirk Keene, Stephen A. Back

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objective: Microvascular brain injury (mVBI) is a common pathological correlate of vascular contributions to cognitive impairment and dementia (VCID) that leads to white matter (WM) injury (WMI). VCID appears to arise from chronic recurrent white matter ischemia that triggers oxidative stress and an increase in total oligodendrocyte lineage cells. We hypothesized that mVBI involves vasodilator dysfunction of white matter penetrating arterioles and aberrant oligodendrocyte progenitor cell (OPC) responses to WMI. Methods: We analyzed cases of mVBI with low Alzheimer's disease neuropathological change in prefrontal cortex WM from rapid autopsies in a population-based cohort where VCID frequently occurs. Arteriolar vasodilator function was quantified by videomicroscopy. OPC maturation was quantified using lineage specific markers. Results: Acetylcholine-mediated arteriolar dilation in mVBI was significantly reduced in WM penetrators relative to pial arterioles. Astrogliosis-defined WMI was positively associated with increased OPCs and was negatively associated with decreased mature oligodendrocytes. Interpretation: Selectively impaired vasodilator function of WM penetrating arterioles in mVBI occurs in association with aberrant differentiation of OPCs in WMI, which supports that myelination disturbances in VCID are related to disrupted maturation of myelinating oligodendrocytes. Ann Neurol 2018;83:142–152.

Original languageEnglish (US)
Pages (from-to)142-152
Number of pages11
JournalAnnals of Neurology
Volume83
Issue number1
DOIs
StatePublished - Jan 2018

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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