Functional deficits induced by cortical microinfarcts

Philipp M. Summers, David A. Hartmann, Edward S. Hui, Xingju Nie, Rachael L. Deardorff, Emilie T. McKinnon, Joseph A. Helpern, Jens H. Jensen, Andy Y. Shih (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

45 Citations (Scopus)

Abstract

Clinical studies have revealed a strong link between increased burden of cerebral microinfarcts and risk for cognitive impairment. Since the sum of tissue damage incurred by microinfarcts is a miniscule percentage of total brain volume, we hypothesized that microinfarcts disrupt brain function beyond the injury site visible to histological or radiological examination. We tested this idea using a mouse model of microinfarcts, where single penetrating vessels that supply mouse cortex were occluded by targeted photothrombosis. We found that in vivo structural and diffusion MRI reliably reported the acute microinfarct core, based on spatial co-registrations with post-mortem stains of neuronal viability. Consistent with our hypothesis, c-Fos assays for neuronal activity and in vivo imaging of single vessel hemodynamics both reported functional deficits in viable peri-lesional tissues beyond the microinfarct core. We estimated that the volume of tissue with functional deficit in cortex was at least 12-fold greater than the volume of the microinfarct core. Impaired hemodynamic responses in peri-lesional tissues persisted at least 14 days, and were attributed to lasting deficits in neuronal circuitry or neurovascular coupling. These data show how individually miniscule microinfarcts could contribute to broader brain dysfunction during vascular cognitive impairment and dementia.

Original languageEnglish
Pages (from-to)3599-3614
Number of pages16
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number11
DOIs
Publication statusPublished - 16 Jan 2017
Externally publishedYes

Keywords

  • microcirculation
  • Microinfarcts
  • neurovascular coupling
  • two-photon microscopy
  • vascular cognitive impairment

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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