title: Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex.
abstract: Small cerebral infarcts, i.e. microinfarcts, are common in the aging brain and linked to vascular cognitive impairment. However, little is known about the acute growth of these minute lesions and their effect on blood flow in surrounding tissues. We modeled microinfarcts in the mouse cortex by inducing photothrombotic clots in single penetrating arterioles. The resultant hemodynamic changes in tissues surrounding the occluded vessel were then studied using in vivo two-photon microscopy. We were able to generate a spectrum of infarct volumes by occluding arterioles that carried a range of blood fluxes. Those resulting from occlusion of high-flux penetrating arterioles (flux of 2 nL/s or higher) exhibited a radial outgrowth that encompassed unusually large tissue volumes. The gradual expansion of these infarcts was propagated by an evolving insufficiency in capillary flow that encroached on territories of neighboring penetrating arterioles, leading to the stagnation and recruitment of their perfusion domains into the final infarct volume. Our results suggest that local collapse of microvascular function contributes to tissue damage incurred by single penetrating arteriole occlusions in mice, and that a similar mechanism may add to pathophysiology induced by microinfarcts of the human brain.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Taylor
authors.affiliation: Department of Diagnostic Radiology, The University of Hong Kong, Hong Kong.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Hui
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Watson
authors.affiliation: Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Xingju
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Deardorff
authors.affiliation: Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Jensen
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Helpern
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA shiha@musc.edu.
authors.forename: Andy Y
authors.initials: AY
authors.lastname: Shih
mesh_terms: D000818:Animals; D001160:Arterioles / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000000981:diagnostic imaging; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D018613:Microscopy, Confocal
keywords: Ischemia; cerebral blood flow; microcirculation; two-photon microscopy; venous thrombosis