Does pathology of small venules contribute to cerebral microinfarcts and dementia?

• Type of Material: Article
• Authors: David A. Hartmann, Medical University of South Carolina; Hyacinth Hyacinth, Emory University; Francesca-Fang Liao, University of Tennessee; Andy Y. Shih, Medical University of South Carolina
• Language: English
• Date: 2018-03-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 International Society for Neurochemistry
• Final Published Version (URL): http://dx.doi.org/10.1111/jnc.14228
• Title of Journal or Parent Work: Journal of Neurochemistry
• ISSN: 0022-3042
• Volume: 144
• Issue: 5
• Start Page: 517
• End Page: 526
• Grant/Funding Information: F.F.L. is supported by NIH 1R21 NS091593-01 and ZEN-16-362441 from Alzheimer's Association.; Our work is supported by grants to A.Y.S. from the NIH-NINDS (NS085402, NS096997), National Science Foundation (1539034), the Dana Foundation, the American Heart Association (14GRNT20480366), South Carolina Clinical and Translational Institute (UL1TR000062), Charleston Conference on Alzheimer’s Disease New Vision Award, and an Institutional Development Award (IDeA) from the NIGMS under grant number P20GM12345.; HIH is supported by NIH-NHLBI (U01HL117721, R01HL138423) and Emory University Pediatrics Center Pilot/HeRO Award; D.A.H. is supported by awards NIH T32 GM08716, NIH-NCATS (UL1 TR001450 and TL1 TR001451), and NIH-NINDS F30NS096868.
• Keywords: venule; Neurosciences; microvascular; Neurosciences & Neurology; ALZHEIMERS-DISEASE; Science & Technology; Life Sciences & Biomedicine; penetrating arteriole; BLOOD-FLOW; venous collagenosis; WHITE-MATTER HYPERINTENSITIES; microinfarct; vascular cognitive impairment; SMALL-VESSEL DISEASE; DEEP MEDULLARY VEINS; CORTICAL MICROINFARCTS; Biochemistry & Molecular Biology; CEREBROVASCULAR-DISEASE; VASCULAR COGNITIVE IMPAIRMENT; AMYLOID ANGIOPATHY; SICKLE-CELL-ANEMIA
• Research Categories: Biology, Neuroscience; Health Sciences, Pharmacology; Health Sciences, Pathology

Abstract

Microinfarcts are small, but strikingly common, ischemic brain lesions in the aging human brain. There is mounting evidence that microinfarcts contribute to vascular cognitive impairment and dementia, but the origins of microinfarcts are unclear. Understanding the vascular pathologies that cause microinfarcts may yield strategies to prevent their occurrence and reduce their deleterious effects on brain function. Current thinking suggests that cortical microinfarcts arise from the occlusion of penetrating arterioles, which are responsible for delivering oxygenated blood to small volumes of tissue. Unexpectedly, pre-clinical studies have shown that the occlusion of penetrating venules, which drain deoxygenated blood from cortex, lead to microinfarcts that appear identical to those resulting from arteriole occlusion. Here we discuss the idea that cerebral venule pathology could be an overlooked source for brain microinfarcts in humans. (Figure presented.). This article is part of the Special Issue “Vascular Dementia”. Cover Image for this Issue: doi: 10.1111/jnc.14167.