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J Cereb Blood Flow Metab. 2017 Nov;37(11):3599-3614. doi: 10.1177/0271678X16685573. Epub 2017 Jan 16.

Functional deficits induced by cortical microinfarcts.

Author information

1
1 Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
2
2 Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong.
3
3 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.
4
4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.

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.

KEYWORDS:

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

PMID:
28090802
PMCID:
PMC5669342
DOI:
10.1177/0271678X16685573
[Indexed for MEDLINE]
Free PMC Article

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