Brain Swelling versus Infarct Size: A Problematizing Review

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke,...

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Published inBrain sciences Vol. 14; no. 3; p. 229
Main Authors Simard, J Marc, Wilhelmy, Bradley, Tsymbalyuk, Natalya, Shim, Bosung, Stokum, Jesse A, Evans, Madison, Gaur, Anandita, Tosun, Cigdem, Keledjian, Kaspar, Ciryam, Prajwal, Serra, Riccardo, Gerzanich, Volodymyr
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Abstract In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.
AbstractList In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.
Audience Academic
Author Simard, J Marc
Tosun, Cigdem
Tsymbalyuk, Natalya
Shim, Bosung
Ciryam, Prajwal
Gerzanich, Volodymyr
Stokum, Jesse A
Serra, Riccardo
Wilhelmy, Bradley
Gaur, Anandita
Keledjian, Kaspar
Evans, Madison
AuthorAffiliation 2 Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
3 Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
1 Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; bradley.wilhelmy@som.umaryland.edu (B.W.); ntsymbalyuk@som.umaryland.edu (N.T.); bosung.shim@som.umaryland.edu (B.S.); jstokum@som.umaryland.edu (J.A.S.); madison.evans@som.umaryland.edu (M.E.); anangaur@terpmail.umd.edu (A.G.); ctosun@som.umaryland.edu (C.T.); kkeledjian@som.umaryland.edu (K.K.); rserra@som.umaryland.edu (R.S.); vgerzanich@som.umaryland.edu (V.G.)
4 Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; pciryam@som.umaryland.edu
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  surname: Gerzanich
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Issue 3
Keywords brain edema
cerebral ischemia
review
SUR1-TRPM4
stroke
middle cerebral artery occlusion
brain swelling
Language English
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SubjectTerms Animal models
brain edema
Brain research
brain swelling
cerebral ischemia
Edema
Genes
Health aspects
Ischemia
middle cerebral artery occlusion
Mortality
Review
Stroke
SUR1-TRPM4
Translation
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Title Brain Swelling versus Infarct Size: A Problematizing Review
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