{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:28:33Z","timestamp":1780986513105,"version":"3.54.1"},"reference-count":184,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"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>Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.<\/jats:p>","DOI":"10.3390\/ijms24097832","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T02:30:52Z","timestamp":1682476252000},"page":"7832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An \u201cHeparin Oriented\u201d Systematic Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-9547","authenticated-orcid":false,"given":"Fulvio","family":"Tartara","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Montalbetti","sequence":"additional","affiliation":[{"name":"A.O.U. Maggiore della Carit\u00e0 University Hospital, Department of Neurosurgery, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Crobeddu","sequence":"additional","affiliation":[{"name":"A.O.U. Maggiore della Carit\u00e0 University Hospital, Department of Neurosurgery, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Armocida","sequence":"additional","affiliation":[{"name":"A.U.O. Policlinico Umberto I, Neurosurgery Division, Human Neurosciences Department, Sapienza University, 00185 Rome, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cardia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Neurocenter of Southern Switzerland, EOC, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cenzato","sequence":"additional","affiliation":[{"name":"Ospedale Niguarda Ca\u2019 Granda, Department of Neurosurgery, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Boeris","sequence":"additional","affiliation":[{"name":"Ospedale Niguarda Ca\u2019 Granda, Department of Neurosurgery, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-7133","authenticated-orcid":false,"given":"Diego","family":"Garbossa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, Neurosurgery Unit, University of Turin, 10095 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Cofano","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Rita Levi Montalcini, Neurosurgery Unit, University of Turin, 10095 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1227\/01.neu.0000430290.93304.33","article-title":"The Epidemiology of Admissions of Nontraumatic Subarachnoid Hemorrhage in the United States","volume":"73","author":"Rincon","year":"2013","journal-title":"Neurosurgery"},{"key":"ref_2","first-page":"e519","article-title":"Cognitive and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage","volume":"41","author":"Macdonald","year":"2010","journal-title":"Stroke"},{"key":"ref_3","first-page":"143","article-title":"Cerebrovascular pathophysiology of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage","volume":"36","author":"Suzuki","year":"2021","journal-title":"Histol. 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