Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage
Open accessAbstract
This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood-brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer's disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke.
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During and after ischemic stroke, blood-brain barrier disruption facilitates injury progression and increases the risk of hemorrhage, predicting poor patient outcome and limiting the use of thrombolytic treatment with recombinant tissue-type plasminogen activator.
“During and after ischemic stroke, BBB disruption facilitates injury progression and increases the risk of hemorrhage, predicting poor patient outcome and limiting the use of thrombolytic treatment with recombinant tissue-type plasminogen activator (tPA) (308, 370).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [308]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe virus can access the brain through the blood stream and infect BBB cells, as observed for other viruses.
“Further, the virus can access the brain through the blood stream and infect BBB cells, as observed for other viruses [131].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [131]
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- Authors
- Keep, R. F., Zhou, N., Xiang, J., Andjelkovic, A. V., Hua, Y., & Xi, G.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Keep, Richard F
- Venue
- Fluids and Barriers of the CNS
- Published
- 2014
- Volume
- 11
- Issue
- 1
- Pages
- 18
- ISSN
- 2045-8118 (ISSN-L)
- PMC
- PMC4130123
- OpenAlex
- W2103156349
- Cited by
- 220
- References
- 144
- Citations by year
- 2026: 22 · 2025: 20 · 2024: 17 · 2023: 19 · 2022: 23 · 2021: 18 · 2020: 29 · 2019: 17 · 2018: 9 · 2017: 24 · 2016: 12 · 2015: 9 · 2014: 1
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Fluids and Barriers of the CNS (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (NS073959, NS079157)
- National Institute of Neurological Disorders and Stroke (R21NS075757, R01NS034709, R21NS084049, R01NS079157)
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- intracerebral hemorrhage, blood-brain barrier dysfunction, hematoma expansion, vascular disruption, thrombin, hemoglobin, iron, neuroinflammation, iron chelation, hematoma evacuation, hypertension, vascular malformations, coagulopathy, Alzheimer's disease, secondary hemorrhage
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