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Cited by 478Barrier Structure and Function StudiesAcute Ischemic Stroke ManagementIntracerebral and Subarachnoid Hemorrhage Research

Blood–brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke

Open access
Khatri, Rakesh, McKinney, Alexander M., Swenson, Barbara, Janardhan, Vallabh·2012·Neurology
DOI 10.1212/wnl.0b013e3182697e70
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Abstract

It has been more than a century since Paul Ehrlich, in 1885, and later his student Edwin Goldmann, proposed that a barrier existed between the CNS and the peripheral circulation. 1 While studying the limited permeation of potassium ferrocyanate into the brain in 1900, Lewandowsky coined the term bluthirnschranke, blood-brain barrier (BBB). 1 The BBB is considered the gatekeeper of the CNS, whose main role is to maintain the fragile homeostasis of the brain designed by segregating the CNS from the systemic circulation.

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  • Blood-brain barrier dysfunction is a prominent pathological feature of both ischemic and hemorrhagic stroke and is typically associated with poor outcome.

    “BBB dysfunction is a prominent pathological feature of both ischemic and hemorrhagic stroke and is typically associated with poor outcome (307, 312, 482).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [312]

    The sections on BBB changes in ischemic stroke and the clinical implications of BBB disruption describe disruption during ischemic stroke and hemorrhagic transformation, and associate a marker of BBB disruption with worse clinical outcome (page not available in our copy). They do not establish the claim for hemorrhagic stroke as a distinct stroke type; hemorrhagic transformation of an ischemic infarct is not the same claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Hemorrhagic stroke transformation is sometimes a consequence of thrombolytic tPA therapy for ischemia, and dysfunctional blood-brain barrier is the primary initiator of the pathology.

    “Hemorrhagic stroke transformation is sometimes a consequence of thrombolytic tPA therapy for ischemia, and dysfunctional BBB is the primary initiator of the pathology (306, 312).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [312]

    The ‘Clinical implication of BBB disruption’ section says hemorrhagic transformation can occur with r-tPA treatment and that thrombolytics amplify its risk. ‘BBB changes during HT’ calls BBB disruption the fundamental mechanism leading to blood extravasation, but describes hemorrhagic transformation as multifactorial and identifies other processes as potential triggers. It therefore does not establish BBB dysfunction as the primary initiator. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 23

  1. Oldendorf WH, Cornford ME, Brown WJ. The large ap- parent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1977;1: 409 -417.
  2. del Zoppo GJ. The neurovascular unit, matrix proteases, and innate inflammation. Ann NY Acad Sci 2010;1207: 46 -49.
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  5. Kulik T, Kusano Y, Aronhime S, Sandler AL, Winn HR. Regulation of cerebral vasculature in normal and ischemic brain. Neuropharmacology 2008;55:281-288.
  6. Kago T, Takagi N, Date I, Takenaga Y, Takagi K, Takeo S. Cerebral ischemia enhances tyrosine phosphorylation of occludin in brain capillaries. Biochem Biophys Res Com- mun 2006;339:1197-1203.
  7. Grossmann J. Molecular mechanisms of "detachment- induced apoptosis-Anoikis." Apoptosis 2002;7:247-260.
  8. Heo JH, Han SW, Lee SK. Free radicals as triggers of brain edema formation after stroke. Free Radic Biol Med 2005; 39:51-70.
  9. Huang WC, Chen JJ, Inoue H, Chen CC. Tyrosine phos- phorylation of I-kappa B kinase alpha/beta by protein kinase C-dependent c-Src activation is involved in TNF- alpha-induced cyclooxygenase-2 expression. J Immunol 2003;170:4767-4775.
  10. Janardhan V, Qureshi AI. Mechanisms of ischemic brain injury. Curr Cardiol Rep 2004;6:117-123.
  11. Warach S, Latour LL. Evidence of reperfusion injury, exac- erbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood- brain barrier disruption. Stroke 2004;35:2659 -2661.
  12. Neumann-Haefelin T, Kastrup A, de Crespigny A, et al. Serial MRI after transient focal cerebral ischemia in rats: dynamics of tissue injury, blood-brain barrier damage, and edema formation. Stroke 2000;31:1965-1973.
  13. Wang X, Tsuji K, Lee SR, et al. Mechanisms of hemor- rhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke. Stroke 2004;35: 2726 -2730.
  14. Castellanos M, Leira R, Serena J, et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 2003;34: 40 -46.
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  17. Yoon W, Seo JJ, Kim JK, Cho KH, Park JG, Kang HK. Contrast enhancement and contrast extravasation on com- puted tomography after intra-arterial thrombolysis in patients with acute ischemic stroke. Stroke 2004;35:876 - 881.
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  19. Wang X, Lo EH. Triggers and mediators of hemorrhagic transformation in cerebral ischemia. Mol Neurobiol 2003; 28:229 -244.
  20. Khatri P, Wechsler LR, Broderick JP. Intracranial hemor- rhage associated with revascularization therapies. Stroke 2007;38:431-440.
  21. Pfefferkorn T, Rosenberg GA. Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion. Stroke 2003;34:2025-2030.
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Cited by

Sorted by citations

Authors
Khatri, R., McKinney, A. M., Swenson, B., & Janardhan, V.
Affiliations
University of Minnesota (US)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-09-25
Volume
79
Issue
13_supplement_1
Pages
S52-7
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0b013e3182697e70
OpenAlex
W2045445343
Cited by
478
References
3
Citations by year
2026: 22 · 2025: 26 · 2024: 34 · 2023: 51 · 2022: 52 · 2021: 55 · 2020: 51 · 2019: 37 · 2018: 42 · 2017: 33 · 2016: 28 · 2015: 22 · 2014: 14 · 2013: 11
FWCI
7.49
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
Keywords
blood-brain barrier, ischemia-reperfusion injury, hemorrhagic transformation, acute ischemic stroke, brain homeostasis
MeSH terms
Animals, Blood-Brain Barrier, Cerebral Hemorrhage, Brain Ischemia, Humans, Reperfusion Injury, Stroke

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