Cerebral microhemorrhages: mechanisms, consequences, and prevention.
The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes, and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs. CMHs are also now recognized by the National Institutes of Health as a major factor in Alzheimer's disease pathology. Moreover, the presence of CMHs is an independent risk factor for subsequent larger intracerebral hemorrhages. In this article, we review the epidemiology, detection, risk factors, clinical significance, and pathogenesis of CMHs. The potential age-related cellular mechanisms underlying the development of CMHs are discussed, with a focus on the structural determinants of microvascular fragility, age-related alterations in cerebrovascular adaptation to hypertension, the role of oxidative stress and matrix metalloproteinase activation, and the deleterious effects of arterial stiffening, increased pulse pressure, and impaired myogenic autoregulatory protection on the brain microvasculature. Finally, we examine potential treatments for the prevention of CMHs based on the proposed model of aging- and hypertension-dependent activation of the reactive oxygen species-matrix metalloproteinases axis, and we discuss critical questions to be addressed by future studies.
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; zoltan-ungvari@ouhsc.edu.|Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Zoltan
Z
Ungvari
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.|Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Stefano
S
Tarantini
Veterans Affairs Medical Center, Oklahoma City, Oklahoma.|Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and.
Angelia C
AC
Kirkpatrick
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.|Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Anna
A
Csiszar
Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Calin I
CI
Prodan
D000367:Age Factors; D000368:Aged; D000375:Aging; D000818:Animals; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control* / Q000523:psychology; D002560:Cerebrovascular Circulation; D003071:Cognition; D003072:Cognition Disorders / Q000453:epidemiology / Q000503:physiopathology / Q000523:psychology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008568:Memory; D008569:Memory Disorders / Q000453:epidemiology / Q000503:physiopathology / Q000523:psychology; D008833:Microcirculation; D055806:Microvessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D066253:Vascular Remodeling
D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases
cerebromicrovascular; cerebrovascular; stroke; transient ischemic attack; vascular aging; vascular cognitive impairment; vascular contributors to cognitive impairment and dementia