{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:25:33Z","timestamp":1773325533018,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"Supplement_3","funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The neurological sequelae of Bacillus anthracis infection include a rapidly progressive fulminant meningoencephalitis frequently associated with intracranial hemorrhage, including subarachnoid and intracerebral hemorrhage. Higher mortality than other forms of bacterial meningitis suggests that antimicrobials and cardiopulmonary support alone may be insufficient and that strategies targeting the hemorrhage might improve outcomes. In this review, we describe the toxic role of intracranial hemorrhage in anthrax meningoencephalitis. We first examine the high incidence of intracranial hemorrhage in patients with anthrax meningoencephalitis. We then review common diseases that present with intracranial hemorrhage, including aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage, postulating applicability of established and potential neurointensive treatments to the multimodal management of hemorrhagic anthrax meningoencephalitis. Finally, we examine the therapeutic potential of minocycline, an antimicrobial that is effective against B. anthracis and that has been shown in preclinical studies to have neuroprotective properties, which thus might be repurposed for this historically fatal disease.<\/jats:p>","DOI":"10.1093\/cid\/ciac521","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T18:49:28Z","timestamp":1666032568000},"page":"S451-S458","source":"Crossref","is-referenced-by-count":13,"title":["Anthrax Meningoencephalitis and Intracranial Hemorrhage"],"prefix":"10.1093","volume":"75","author":[{"given":"Nicholas","family":"Caffes","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Hendricks","sequence":"additional","affiliation":[{"name":"Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, San Diego School of Medicine and Rady Children\u2019s Hospital, University of California , San Diego, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy A","family":"Twenhafel","sequence":"additional","affiliation":[{"name":"Division of Pathology, United States Army Medical Research Institute of Infectious Diseases , Frederick, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-1988","authenticated-orcid":false,"given":"J Marc","family":"Simard","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery, Pathology and Physiology, University of Maryland School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"2022113009500657400_ciac521-B1","doi-asserted-by":"crossref","DOI":"10.3201\/eid2002.130687","article-title":"Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults","volume":"20","author":"Hendricks","year":"2014","journal-title":"Emerg Infect Dis"},{"key":"2022113009500657400_ciac521-B2","doi-asserted-by":"crossref","first-page":"S364","DOI":"10.1093\/cid\/ciac531","article-title":"Survival of patient with hemorrhagic meningitis associated with inhalation anthrax","volume":"75","author":"Lombarte Espinosa","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2022113009500657400_ciac521-B3","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fncel.2015.00080","article-title":"The choroid plexus\u2014a multi-role player during infectious diseases of the CNS","volume":"9","author":"Schwerk","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"2022113009500657400_ciac521-B4","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/01.LAB.0000080599.43791.01","article-title":"Pathology of inhalation anthrax in cynomolgus monkeys (Macaca fascicularis)","volume":"83","author":"Vasconcelos","year":"2003","journal-title":"Lab Invest"},{"key":"2022113009500657400_ciac521-B5","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.annemergmed.2005.11.035","article-title":"Anthrax: a systematic review of atypical presentations","volume":"48","author":"Holty","year":"2006","journal-title":"Ann Emerg Med"},{"key":"2022113009500657400_ciac521-B6","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1177\/0300985810378112","article-title":"Pathology of inhalational anthrax animal models","volume":"47","author":"Twenhafel","year":"2010","journal-title":"Vet Pathol"},{"key":"2022113009500657400_ciac521-B7","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1073\/pnas.90.6.2291","article-title":"Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979","volume":"90","author":"Abramova","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022113009500657400_ciac521-B8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mib.2003.12.001","article-title":"The roles of anthrax toxin in pathogenesis","volume":"7","author":"Moayeri","year":"2004","journal-title":"Curr Opin Microbiol"},{"key":"2022113009500657400_ciac521-B9","doi-asserted-by":"crossref","first-page":"e17921","DOI":"10.1371\/journal.pone.0017921","article-title":"Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages","volume":"6","author":"Mukherjee","year":"2011","journal-title":"PLoS One"},{"key":"2022113009500657400_ciac521-B10","first-page":"691","article-title":"Pathology of experimental inhalation anthrax in the rhesus monkey","volume":"73","author":"Fritz","year":"1995","journal-title":"Lab Invest"},{"key":"2022113009500657400_ciac521-B11","first-page":"1303","article-title":"CT and MR findings of anthrax meningoencephalitis: report of two cases and review of the literature","volume":"22","author":"Kim","year":"2001","journal-title":"AJNR Am J Neuroradiol"},{"key":"2022113009500657400_ciac521-B12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/00000441-195207000-00009","article-title":"Anthrax meningitis: review of literature and report of two cases with autopsies","volume":"224","author":"Haight","year":"1952","journal-title":"Am J Med Sci"},{"key":"2022113009500657400_ciac521-B13","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1093\/cid\/ciw184","article-title":"Identifying meningitis during an anthrax mass casualty incident: systematic review of systemic anthrax since 1880","volume":"62","author":"Katharios-Lanwermeyer","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2022113009500657400_ciac521-B14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1212\/WNL.59.3.327","article-title":"Anthrax meningoencephalitis","volume":"59","author":"Lanska","year":"2002","journal-title":"Neurology"},{"key":"2022113009500657400_ciac521-B15","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1212\/WNL.25.6.525","article-title":"Bacillus anthracis meningitis","volume":"25","author":"Rangel","year":"1975","journal-title":"Neurology"},{"key":"2022113009500657400_ciac521-B16","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22105132","article-title":"When the blood hits your brain: the neurotoxicity of extravasated blood","volume":"22","author":"Stokum","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2022113009500657400_ciac521-B17","doi-asserted-by":"crossref","first-page":"10281","DOI":"10.1523\/JNEUROSCI.2806-06.2006","article-title":"Combination of thrombin and matrix metalloproteinase-9 exacerbates neurotoxicity in cell culture and intracerebral hemorrhage in mice","volume":"26","author":"Xue","year":"2006","journal-title":"J Neurosci"},{"key":"2022113009500657400_ciac521-B18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0006-8993(82)90147-0","article-title":"Formation of malonaldehyde and focal brain edema induced by subpial injection of FeCl2 into rat isocortex","volume":"246","author":"Willmore","year":"1982","journal-title":"Brain Res"},{"key":"2022113009500657400_ciac521-B19","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1179\/135100009X12525712409931","article-title":"Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke","volume":"14","author":"Robinson","year":"2009","journal-title":"Redox Rep"},{"key":"2022113009500657400_ciac521-B20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/cc8983","article-title":"Hypertension may be the most important component of hyperdynamic therapy in cerebral vasospasm","volume":"14","author":"Harrigan","year":"2010","journal-title":"Crit Care"},{"key":"2022113009500657400_ciac521-B21","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1111\/cns.13222","article-title":"Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage","volume":"25","author":"Daou","year":"2019","journal-title":"CNS Neurosci Ther"},{"key":"2022113009500657400_ciac521-B22","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1172\/JCI114475","article-title":"Loss of cerebrovascular autoregulation in experimental meningitis in rabbits","volume":"85","author":"Tureen","year":"1990","journal-title":"J Clin Invest"},{"key":"2022113009500657400_ciac521-B23","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1097\/00003246-200004000-00019","article-title":"Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis","volume":"28","author":"Moller","year":"2000","journal-title":"Crit Care Med"},{"key":"2022113009500657400_ciac521-B24","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1136\/bmj.298.6674.636","article-title":"Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial","volume":"298","author":"Pickard","year":"1989","journal-title":"BMJ"},{"key":"2022113009500657400_ciac521-B25","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1097\/00003246-200007000-00060","article-title":"Reduction of intracranial pressure by nimodipine in experimental pneumococcal meningitis","volume":"28","author":"Paul","year":"2000","journal-title":"Crit Care Med"},{"key":"2022113009500657400_ciac521-B26","first-page":"271","article-title":"Effects of nimodipine on the cerebrovascular and neuronal changes during pneumococcal meningitis in the rat","volume":"44","author":"Hosoglu","year":"1997","journal-title":"Acta Microbiol Immunol Hung"},{"key":"2022113009500657400_ciac521-B27","doi-asserted-by":"crossref","DOI":"10.1111\/jnc.14324","article-title":"Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis [manuscript published online ahead of print 23 February 2018]","author":"Ingwersen","year":"2018","journal-title":"J Neurochem"},{"key":"2022113009500657400_ciac521-B28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0022-510X(01)00529-9","article-title":"Use of statins in CNS disorders","volume":"187","author":"Cucchiara","year":"2001","journal-title":"J Neurol Sci"},{"key":"2022113009500657400_ciac521-B29","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1161\/STROKEAHA.107.508341","article-title":"Do statins improve outcomes and reduce the incidence of vasospasm after aneurysmal subarachnoid hemorrhage: a meta-analysis","volume":"39","author":"Sillberg","year":"2008","journal-title":"Stroke"},{"key":"2022113009500657400_ciac521-B30","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1161\/STROKEAHA.109.556332","article-title":"Effect of statin treatment on vasospasm, delayed cerebral ischemia, and functional outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update","volume":"41","author":"Vergouwen","year":"2010","journal-title":"Stroke"},{"key":"2022113009500657400_ciac521-B31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.intimp.2008.11.019","article-title":"Simvastatin attenuates leukocyte recruitment in experimental bacterial meningitis","volume":"9","author":"Winkler","year":"2009","journal-title":"Int Immunopharmacol"},{"key":"2022113009500657400_ciac521-B32","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.3389\/fimmu.2018.02137","article-title":"Prophylactic treatment with simvastatin modulates the immune response and increases animal survival following lethal sepsis infection","volume":"9","author":"Braga Filho","year":"2018","journal-title":"Front Immunol"},{"key":"2022113009500657400_ciac521-B33","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1212\/WNL.0000000000000917","article-title":"Intensive blood pressure reduction in acute intracerebral hemorrhage: a meta-analysis","volume":"83","author":"Tsivgoulis","year":"2014","journal-title":"Neurology"},{"key":"2022113009500657400_ciac521-B34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrneurol.2014.264","article-title":"Targeting secondary injury in intracerebral haemorrhage\u2014perihaematomal oedema","volume":"11","author":"Urday","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"2022113009500657400_ciac521-B35","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1161\/STROKEAHA.115.010054","article-title":"Perihematomal edema and functional outcomes in intracerebral hemorrhage: influence of hematoma volume and location","volume":"46","author":"Murthy","year":"2015","journal-title":"Stroke"},{"key":"2022113009500657400_ciac521-B36","first-page":"21","article-title":"Current management of spontaneous intracerebral haemorrhage","volume":"2","author":"Dastur","year":"2017","journal-title":"BMJ"},{"key":"2022113009500657400_ciac521-B37","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1161\/STROKEAHA.115.009357","article-title":"Mannitol and outcome in intracerebral hemorrhage: propensity score and multivariable intensive blood pressure reduction in acute cerebral hemorrhage trial 2 results","volume":"46","author":"Wang","year":"2015","journal-title":"Stroke"},{"key":"2022113009500657400_ciac521-B38","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1097\/CCM.0b013e3182120d13","article-title":"Superior effect of hypertonic saline over mannitol to attenuate cerebral edema in a rabbit bacterial meningitis model","volume":"39","author":"Liu","year":"2011","journal-title":"Crit Care Med"},{"key":"2022113009500657400_ciac521-B39","doi-asserted-by":"crossref","first-page":"104050","DOI":"10.1016\/j.micpath.2020.104050","article-title":"Combinations of early generation antibiotics and antimicrobial peptides are effective against a broad spectrum of bacterial biothreat agents","volume":"142","author":"Cote","year":"2020","journal-title":"Microb Pathog"},{"key":"2022113009500657400_ciac521-B40","first-page":"31","article-title":"Comparison of therapeutic effects of antibiotics of the tetracycline group in the treatment of anthrax caused by a strain inheriting tet-gene of plasmid pBC16 [in Russian]","volume":"37","author":"Pomerantsev","year":"1992","journal-title":"Antibiot Khimioter"},{"key":"2022113009500657400_ciac521-B41","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1128\/AAC.8.6.713","article-title":"Relation between lipophilicity and pharmacological behavior of minocycline, doxycycline, tetracycline, and oxytetracycline in dogs","volume":"8","author":"Barza","year":"1975","journal-title":"Antimicrob Agents Chemother"},{"key":"2022113009500657400_ciac521-B42","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/1073858405275175","article-title":"Minocycline as a neuroprotective agent","volume":"11","author":"Stirling","year":"2005","journal-title":"Neuroscientist"},{"key":"2022113009500657400_ciac521-B43","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.bcp.2009.07.028","article-title":"Mitochondria and calcium flux as targets of neuroprotection caused by minocycline in cerebellar granule cells","volume":"79","author":"Garcia-Martinez","year":"2010","journal-title":"Biochem Pharmacol"},{"key":"2022113009500657400_ciac521-B44","doi-asserted-by":"crossref","first-page":"9685","DOI":"10.1073\/pnas.0600554103","article-title":"Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations","volume":"103","author":"Alano","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022113009500657400_ciac521-B45","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s00415-018-8935-3","article-title":"Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials","volume":"265","author":"Malhotra","year":"2018","journal-title":"J Neurol"},{"key":"2022113009500657400_ciac521-B46","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1128\/AAC.1.5.397","article-title":"Minocycline in the chemoprophylaxis of meningococcal disease","volume":"1","author":"Guttler","year":"1972","journal-title":"Antimicrob Agents Chemother"},{"key":"2022113009500657400_ciac521-B47","doi-asserted-by":"crossref","first-page":"834","DOI":"10.2174\/187152711798072383","article-title":"Meta-analysis of the effectiveness and safety of prophylactic use of nimodipine in patients with an aneurysmal subarachnoid haemorrhage","volume":"10","author":"Liu","year":"2011","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"2022113009500657400_ciac521-B48","doi-asserted-by":"crossref","first-page":"14345","DOI":"10.1038\/s41598-017-13111-x","article-title":"Blood pressure management for acute intracerebral hemorrhage: a meta-analysis","volume":"7","author":"Shi","year":"2017","journal-title":"Sci Rep"},{"key":"2022113009500657400_ciac521-B49","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/CCM.0b013e318206b9be","article-title":"Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials","volume":"39","author":"Kamel","year":"2011","journal-title":"Crit Care Med"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/Supplement_3\/S451\/47446016\/ciac521.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/Supplement_3\/S451\/47446016\/ciac521.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T14:54:23Z","timestamp":1669820063000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/75\/Supplement_3\/S451\/6762179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,15]]},"references-count":49,"journal-issue":{"issue":"Supplement_3","published-online":{"date-parts":[[2022,10,17]]},"published-print":{"date-parts":[[2022,10,17]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac521","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10,15]]},"published":{"date-parts":[[2022,10,15]]}}}