{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:00:39Z","timestamp":1793736039542,"version":"4.6.1"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza, University of Rome","doi-asserted-by":"publisher","award":["AR11916B89103E01"],"award-info":[{"award-number":["AR11916B89103E01"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perihematomal hypoperfusion may lead to ischemic damage during intraparenchymal cerebral hemorrhage (ICH), resulting in worse prognosis. We aimed to (1) investigate the relationship between serum biomarkers related to oxidative stress and vasoactive substances and the occurrence of hypoperfusion and ischemic perihematomal lesions in ICH and (2) evaluate their correlation with the volumetric evolution of the hematoma and perihematomal edema. We enrolled 28 patients affected by ICH. Blood samples were collected at three different time points from symptom onset: T0, T1, and T2 (admission, 12\u201324 h, and 48\u201372 h, respectively), to measure endothelin-1 (ET-1), nitrites\/nitrates (NO), soluble nicotinamide adenine dinucleotide 2 (NOX2)-derived peptide (sNOX2-dp), and asymmetric dimethylarginine (ADMA). Patients underwent brain MRI with perfusion study at T1 and MRI without perfusion at T2. 12 patients had ischemic perihematomal lesions at T1. A higher sNOX2-dp concentration at T0 was observed in patients with ischemic perihematomal lesions compared to those without (p = 0.051) and with a more severe perihematomal edema at T2 (p = 0.011). The ischemic perihematomal lesions development was also associated with an increased hematoma volume (p &lt; 0.005), perilesional edema (p = 0.046), and greater midline shift (p = 0.036). ET-1 values at T1 were inversely correlated with hemorrhage volume at T2 (\u03c1 = \u22120.717, p = 0.030). NOX2 activation may have a role in the development of ischemic perihematomal lesions. The association between higher ET-1 values and a lower hemorrhage volume could be related to the ET-1 vasoconstriction action on the ruptured vessel wall.<\/jats:p>","DOI":"10.3390\/ijms252313180","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T04:01:37Z","timestamp":1733716897000},"page":"13180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Secondary Brain Injury After Parenchymal Cerebral Hemorrhage in Humans: The Role of NOX2-Mediated Oxidative Stress and Endothelin-1"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-4309","authenticated-orcid":false,"given":"Manuela","family":"De Michele","sequence":"first","affiliation":[{"name":"Stroke Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-9408","authenticated-orcid":false,"given":"Paolo","family":"Amisano","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar G.","family":"Schiavo","sequence":"additional","affiliation":[{"name":"Stroke Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-5945","authenticated-orcid":false,"given":"Vittoria","family":"Cammisotto","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-9595","authenticated-orcid":false,"given":"Roberto","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University, 04100 Latina, Italy"},{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-0534","authenticated-orcid":false,"given":"Maurizio","family":"Forte","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1591-5118","authenticated-orcid":false,"given":"Vittorio","family":"Picchio","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3282-4672","authenticated-orcid":false,"given":"Antonio","family":"Ciacciarelli","sequence":"additional","affiliation":[{"name":"Stroke Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Berto","sequence":"additional","affiliation":[{"name":"Stroke Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Angeloni","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Umberto I Hospital, Emergency Department, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Toni","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Lorenzano","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Stroke Collaborators (2021). 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