title: Functional deficits induced by cortical microinfarcts.
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.
authors.affiliation: 1 Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Summers
authors.affiliation: 1 Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hartmann
authors.affiliation: 2 Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Hui
authors.affiliation: 3 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Xingju
authors.initials: X
authors.lastname: Nie
authors.affiliation: 3 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Deardorff
authors.affiliation: 3 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Emilie T
authors.initials: ET
authors.lastname: McKinnon
authors.affiliation: 1 Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.|3 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Helpern
authors.affiliation: 3 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.|4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Jensen
authors.affiliation: 1 Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.|4 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Andy Y
authors.initials: AY
authors.lastname: Shih
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000523:psychology*; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000523:psychology*; D007150:Immunohistochemistry; D020767:Intracranial Thrombosis / Q000150:complications / Q000000981:diagnostic imaging / Q000523:psychology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D010812:Physical Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D013569:Synapses / Q000473:pathology; D014738:Vibrissae
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Microinfarcts; microcirculation; neurovascular coupling; two-photon microscopy; vascular cognitive impairment