{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:55:33Z","timestamp":1790823333068,"version":"4.1.0"},"reference-count":234,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked. Since trials of surgical intervention to remove CNS hemorrhage have been generally unsuccessful, the potent neurotoxicity of blood is generally viewed as a basic scientific curiosity rather than a clinically meaningful factor. In this review, we evaluate the direct role of blood as a neurotoxin and its subsequent clinical relevance. We first describe the molecular mechanisms of blood neurotoxicity. We then evaluate the clinical literature that directly relates to the evacuation of CNS hemorrhage. We posit that the efficacy of clot removal is a critical factor in outcome following surgical intervention. Future interventions for CNS hemorrhage should be guided by the principle that blood is exquisitely toxic to the brain.<\/jats:p>","DOI":"10.3390\/ijms22105132","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T22:46:14Z","timestamp":1620859574000},"page":"5132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["When the Blood Hits Your Brain: The Neurotoxicity of Extravasated Blood"],"prefix":"10.3390","volume":"22","author":[{"given":"Jesse A.","family":"Stokum","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0728-511X","authenticated-orcid":false,"given":"Gregory J.","family":"Cannarsa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Wessell","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phelan","family":"Shea","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Wenger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-1988","authenticated-orcid":false,"given":"J. Marc","family":"Simard","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Departments of Pathology and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1212\/01.wnl.0000304930.47751.75","article-title":"Intraventricular hemorrhage: Anatomic relationships and clinical implications","volume":"70","author":"Hallevi","year":"2008","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.5853\/jos.2016.00864","article-title":"Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update","volume":"19","author":"An","year":"2017","journal-title":"J. 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