{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:38:52Z","timestamp":1788475132141,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biochemistry and Medical Chemistry at Pomeranian Medical University in Szczecin, Poland","award":["RID\/SP\/0045\/2024\/01"],"award-info":[{"award-number":["RID\/SP\/0045\/2024\/01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute brain injury includes different pathologies: stroke, traumatic injury, subarachnoidale haemorhhage. In the pathophysiology of acute brain injury, secondary injury with hyperactivation of glia plays a crucial role. Activated glial cells induce prolonged inflammation that impacts the recovery and further cognitive functions of patients. In our study, we have examined the neuroprotective impact of exogenous neuropeptides\u2014Cerebrolysin on astrocytes under different conditions. In a model that simulates central nervous system damage associated with brain injury, stroke, and subarachnoid hemorrhage, the U87MG human brain cancer (glioblastoma astrocytoma like) cells were treated with Cerebrolysin and exposed to conditions of continuous and cyclic hypoxia and red blood cell lysate overload. The activity and expression of cyclooxygenases COX-1 and COX-2 and on cytokines (IL-8, IL-1\u03b2, IL-6, IL-10) and chemokines (CCL5\/RANTES, CXCL9\/MIG, CCL2\/MCP-1, and CXCL10\/IP-10) concentration were assessed. Cerebrolysin lowers IL-1\u03b2 and IL-6 and increases IL-10 under all conditions. Cerebrolysin may exhibit a neuroimmunotrophic function, reducing inflammation under conditions that replicate traumatic brain injury and hemorrhagic insults to the central nervous system. By modulating both pro-inflammatory and anti-inflammatory cytokines, Cerebrolysin can help create a more balanced immune response conducive to tissue repair and reduced secondary damage. Its ability to lower harmful mediators like IL-1\u03b2 and IL-6 while enhancing protective factors such as IL-10 suggests a promising therapeutic strategy in stroke, traumatic brain injury, and subarachnoid hemorrhage. Alongside other mechanisms such as neurotrophic factor enhancement and glial cell regulation, this cytokine modulation underscores the therapeutic potential of Cerebrolysin in a variety of central nervous system disorders.<\/jats:p>","DOI":"10.3390\/ijms26093953","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"3953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Influence of Exogenous Neuropeptides on the Astrocyte Response Under Conditions of Continuous and Cyclic Hypoxia and Red Blood Cell Lysate"],"prefix":"10.3390","volume":"26","author":[{"given":"Klaudyna","family":"Kojder","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin, Rybacka 1, 70-204 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9777-1378","authenticated-orcid":false,"given":"Magdalena","family":"G\u0105ssowska-Dobrowolska","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-7120","authenticated-orcid":false,"given":"Wojciech","family":"\u017bwiere\u0142\u0142o","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0686-3953","authenticated-orcid":false,"given":"Patrycja","family":"K\u0142os","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-0830","authenticated-orcid":false,"given":"Katarzyna","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Wszo\u0142ek","sequence":"additional","affiliation":[{"name":"Institute of Biology, University of Szczecin, W\u0105ska 13, 71-415 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-9717","authenticated-orcid":false,"given":"Agnieszka","family":"Maruszewska","sequence":"additional","affiliation":[{"name":"Institute of Biology, University of Szczecin, W\u0105ska 13, 71-415 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Gutowska","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-4395","authenticated-orcid":false,"given":"Dariusz","family":"Chlubek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-8895","authenticated-orcid":false,"given":"Irena","family":"Baranowska-Bosiacka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1093\/brain\/awl165","article-title":"Essential protective roles of reactive astrocytes in traumatic brain injury","volume":"129","author":"Myer","year":"2006","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1089\/neu.2015.4126","article-title":"Epidemiology of traumatic brain injury in Europe: A living systematic review","volume":"38","author":"Brazinova","year":"2021","journal-title":"J. Neurotrauma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/SHK.0000000000002014","article-title":"Multimodal treatment approaches to combined traumatic brain injury and hemorrhagic shock alter postinjury inflammatory response","volume":"58","author":"Wallen","year":"2022","journal-title":"Shock"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1400808","DOI":"10.3389\/fnmol.2024.1400808","article-title":"Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk","volume":"17","author":"Xie","year":"2024","journal-title":"Front. Mol. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1097\/00006123-199802000-00091","article-title":"Acute vasoconstriction after subarachnoid hemorrhage","volume":"42","author":"Bederson","year":"1998","journal-title":"Neurosurgery"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.pneurobio.2012.02.003","article-title":"The importance of early brain injury after subarachnoid hemorrhage","volume":"97","author":"Sehba","year":"2012","journal-title":"Prog. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3171\/jns.2004.101.4.0633","article-title":"Acute alterations in microvascular basal lamina after subarachnoid hemorrhage","volume":"101","author":"Sehba","year":"2004","journal-title":"J. Neurosurg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.3171\/jns.2005.102.6.1094","article-title":"Acute microvascular platelet aggregation after subarachnoid hemorrhage","volume":"102","author":"Sehba","year":"2005","journal-title":"DidnJ. Neurosurg."},{"key":"ref_9","first-page":"1082","article-title":"Inflammation in the brain after experimental subarachnoid hemorrhage","volume":"56","author":"Prunell","year":"2005","journal-title":"Neurosurgery"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1161\/STROKEAHA.122.037155","article-title":"Role of inflammatory processes in hemorrhagic stroke","volume":"54","author":"Ohashi","year":"2023","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.4049\/jimmunol.0902023","article-title":"Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression","volume":"184","author":"Ren","year":"2010","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1227\/01.NEU.0000068863.37133.9E","article-title":"Cerebral vasospasm after subarachnoid hemorrhage: Putative role of inflammation","volume":"53","author":"Dumont","year":"2003","journal-title":"Neurosurgery"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1089\/neu.2013.3087","article-title":"Post-traumatic hypoxia is associated with prolonged cerebral cytokine production, higher serum biomarker levels, and poor outcome in patients with severe traumatic brain injury","volume":"31","author":"Yan","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1186\/1742-2094-10-83","article-title":"The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage","volume":"10","author":"Hanafy","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13375","DOI":"10.1523\/JNEUROSCI.1551-15.2015","article-title":"Astrocyte Ca2+ signaling drives inversion of neurovascular coupling after subarachnoid hemorrhage","volume":"35","author":"Pappas","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2018.07.021","article-title":"Astrocyte activation and reactive gliosis\u2014A new target in stroke?","volume":"689","author":"Pekny","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Luo, C., Yao, J., Bi, H., Li, Z., Li, J., Xue, G., Li, K., Zhang, S., Zan, K., and Meng, W. (2022). Clinical value of inflammatory cytokines in patients with aneurysmal subarachnoid hemorrhage. Clin. Interv. Aging, 615\u2013626.","DOI":"10.2147\/CIA.S362854"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/sj.jcbfm.9600403","article-title":"Inflammation after intracerebral hemorrhage","volume":"27","author":"Wang","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/S0959-440X(01)00277-9","article-title":"Cyclooxygenase enzymes: Catalysis and inhibition","volume":"11","author":"Kurumbail","year":"2001","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jpain.2006.10.004","article-title":"Expression of COX-1 and COX-2 in a clinical model of acute inflammation","volume":"8","author":"Khan","year":"2007","journal-title":"J. Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.3892\/ol.2017.6094","article-title":"Blueberries inhibit cyclooxygenase-1 and cyclooxygenase-2 activity in human epithelial ovarian cancer","volume":"13","author":"Lin","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0090-6980(02)00029-1","article-title":"Distinct functions of COX-1 and COX-2","volume":"68\u201369","author":"Morita","year":"2002","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"960","DOI":"10.3892\/ijmm.2012.1052","article-title":"Transcriptional and translational regulation of COX-2 expression by cadmium in C6 glioma cells","volume":"30","author":"Park","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.3171\/2017.6.JNS171007","article-title":"Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury","volume":"129","author":"Zhang","year":"2018","journal-title":"J. Neurosurg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1007\/s12031-022-02078-8","article-title":"Cerebrolysin alleviating effect on glutamate-mediated neuroinflammation via glutamate transporters and oxidative stress","volume":"72","author":"Avci","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e370605","DOI":"10.1590\/acb370605","article-title":"Cerebrolysin alleviates early brain injury after traumatic brain injury by inhibiting neuroinflammation and apoptosis via TLR signaling pathway","volume":"37","author":"Lu","year":"2022","journal-title":"Acta Cir. Bras."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0091-3057(98)00144-0","article-title":"Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice","volume":"62","author":"Masliah","year":"1999","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3109\/02688697.2013.793287","article-title":"Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: Double-blind, placebo-controlled, randomized study","volume":"27","author":"Chen","year":"2013","journal-title":"Br. J. Neurosurg."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhang, D., Dong, Y., Li, Y., Chen, J., Wang, J., and Hou, L. (2017). Efficacy and Safety of Cerebrolysin for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/4191670"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"910697","DOI":"10.3389\/fneur.2022.910697","article-title":"Efficacy of cerebrolysin treatment as an add-on therapy to mechanical thrombectomy in patients with acute ischemic stroke due to large vessel occlusion: Study protocol for a prospective, open label, single-center study with 12 Months of follow-up","volume":"13","author":"Staszewski","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/1545968318809916","article-title":"Cerebrolysin reduces astrogliosis and axonal injury and enhances neurogenesis in rats after closed head injury","volume":"33","author":"Zhang","year":"2019","journal-title":"Neurorehabilit. Neural Repair"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0168-0102(99)00056-5","article-title":"In vivo upregulation of the blood\u2013brain barrier GLUT1 glucose transporter by brain-derived peptides","volume":"34","author":"Boado","year":"1999","journal-title":"Neurosci. Res."},{"key":"ref_33","first-page":"350","article-title":"Neuroprotective and consequent neurorehabilitative clinical outcomes, in patients treated with the pleiotropic drug cerebrolysin","volume":"2","author":"Onose","year":"2009","journal-title":"J. Med. Life"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.3389\/fphar.2019.01245","article-title":"Cerebrolysin ameliorates focal cerebral ischemia injury through neuroinflammatory inhibition via CREB\/PGC-1\u03b1 pathway","volume":"10","author":"Guan","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1161\/STROKEAHA.111.628537","article-title":"Cerebrolysin in patients with acute ischemic stroke in Asia: Results of a double-blind, placebo-controlled randomized trial","volume":"43","author":"Heiss","year":"2012","journal-title":"Stroke"},{"key":"ref_36","first-page":"2299","article-title":"Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke","volume":"10","author":"Nazarbaghi","year":"2014","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s007020170067","article-title":"Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons","volume":"108","author":"Hartbauer","year":"2001","journal-title":"J. Neural Transm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/10298420290007637","article-title":"In vitro models of brain ischemia: The peptidergic drug cerebrolysin protects cultured chick cortical neurons from cell death","volume":"4","author":"Gutmann","year":"2002","journal-title":"Neurotox. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00702-005-0302-8","article-title":"A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication","volume":"113","author":"Riley","year":"2006","journal-title":"J. Neural Transm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00702-005-0384-3","article-title":"Neuroprotection of cerebrolysin in tissue culture models of brain ischemia: Post lesion application indicates a wide therapeutic window","volume":"113","author":"Schauer","year":"2006","journal-title":"J. Neural Transm."},{"key":"ref_41","first-page":"25","article-title":"Cerebrolysin enhances functional recovery following focal cerebral infarction in rats","volume":"25","author":"Ren","year":"2007","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1166\/ajnn.2009.1010","article-title":"Cerebrolysin reduces infarct volume in a rat model of focal cerebral ischemic damage","volume":"1","author":"Hanson","year":"2009","journal-title":"Am. J. Neuroprot. Neuroregener."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Woo, P.Y.M., Ho, J.W.K., Ko, N.M.W., Li, R.P.T., Jian, L., Chu, A.C.H., Kwan, M.C.L., Chan, Y., Wong, A.K.S., and Wong, H.-T. (2020). Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage. BMC Neurol., 20.","DOI":"10.1186\/s12883-020-01908-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3389\/fneur.2017.00244","article-title":"Role of interleukin-10 in acute brain injuries","volume":"8","author":"Garcia","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00011-015-0895-9","article-title":"Anti-inflammatory effects of fimasartan via Akt, ERK, and NFkappaB pathways on astrocytes stimulated by hemolysate","volume":"65","author":"Yang","year":"2016","journal-title":"Inflamm. Res."},{"key":"ref_46","first-page":"137","article-title":"Efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke","volume":"3","author":"Bajenaru","year":"2010","journal-title":"J. Med. Life"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jacquens, A., Needham, E.J., Zanier, E.R., Degos, V., Gressens, P., and Menon, D. (2022). Neuro-inflammation modulation and post-traumatic brain injury lesions: From bench to bed-side. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911193"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"973","DOI":"10.4103\/NRR.NRR-D-23-02091","article-title":"Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury","volume":"20","author":"Cieri","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.mcn.2007.07.005","article-title":"Interleukin-1\u03b2 mediates proliferation and differentiation of multipotent neural precursor cells through the activation of SAPK\/JNK pathway","volume":"36","author":"Wang","year":"2007","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1471-4159.2007.04558.x","article-title":"Arachidonic acid metabolism in brain physiology and pathology: Lessons from genetically altered mouse models","volume":"102","author":"Bosetti","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"L1094","DOI":"10.1152\/ajplung.2001.280.6.L1094","article-title":"IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways","volume":"280","author":"Schraufstatter","year":"2001","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/00004647-199703000-00005","article-title":"Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood\u2013brain barrier dysfunction and nerve growth factor production","volume":"17","author":"Kossmann","year":"1997","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.3109\/02699052.2014.916818","article-title":"Increased levels of interleukin-6,-8 and-10 are associated with fatal outcome following severe traumatic brain injury","volume":"28","author":"Ferreira","year":"2014","journal-title":"Brain Inj."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1620\/tjem.211.387","article-title":"Plasma interleukin-8 as a potential predictor of mortality in adult patients with severe traumatic brain injury","volume":"211","author":"Gopcevic","year":"2007","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cyto.2018.01.012","article-title":"Pro-and anti-inflammatory biomarkers and traumatic brain injury outcomes: A review","volume":"110","author":"Rodney","year":"2018","journal-title":"Cytokine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1131","DOI":"10.1016\/j.wneu.2019.05.102","article-title":"Plasma levels of IL-6, IL-8, IL-10, ICAM-1, VCAM-1, IFN\u03b3, and TNF\u03b1 are not associated with delayed cerebral ischemia, cerebral vasospasm, or clinical outcome in patients with subarachnoid hemorrhage","volume":"128","author":"Rasmussen","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_57","first-page":"141","article-title":"Increase of the IL-1beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH","volume":"25","author":"Hendryk","year":"2004","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.3889\/oamjms.2018.390","article-title":"High Il-1\u03b2 Serum as a Predictor of Decreased Cognitive Function in Mild Traumatic Brain Injury Patients","volume":"6","author":"Samatra","year":"2018","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1161\/STROKEAHA.109.549592","article-title":"Role of interleukin-1\u03b2 in early brain injury after subarachnoid hemorrhage in mice","volume":"40","author":"Sozen","year":"2009","journal-title":"Stroke"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/156720210790820226","article-title":"Interleukin-1\u03b2 plays a role in the activation of peripheral leukocytes after blood-brain barrier rupture in the course of subarachnoid hemorrhage","volume":"7","author":"Straszak","year":"2010","journal-title":"Curr. Neurovascular Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e362","DOI":"10.1016\/j.wneu.2017.12.076","article-title":"Levels of interleukin-1\u03b2, interleukin-18, and tumor necrosis factor-\u03b1 in cerebrospinal fluid of aneurysmal subarachnoid hemorrhage patients may be predictors of early brain injury and clinical prognosis","volume":"111","author":"Lv","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"828447","DOI":"10.3389\/fimmu.2022.828447","article-title":"Interleukins and ischemic stroke","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s10072-017-3214-0","article-title":"Safety and efficacy of Cerebrolysin in early post-stroke recovery: A meta-analysis of nine randomized clinical trials","volume":"39","author":"Bornstein","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s10072-019-04181-y","article-title":"Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: Results from the CAPTAIN II trial","volume":"41","author":"Muresanu","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Jarosz, K., Kojder, K., Andrzejewska, A., Solek-Pastuszka, J., and Jurczak, A. (2023). Cerebrolysin in patients with TBI: Systematic review and meta-analysis. Brain Sci., 13.","DOI":"10.3390\/brainsci13030507"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1007\/s12325-018-0832-8","article-title":"Cerebrolysin for the treatment of aneurysmal subarachnoid hemorrhage in adults: A retrospective chart review","volume":"35","author":"Park","year":"2018","journal-title":"Adv. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1172\/JCI65167","article-title":"MFGE8 inhibits inflammasome-induced IL-1\u03b2 production and limits postischemic cerebral injury","volume":"123","author":"Deroide","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/01.WCB.0000073905.87928.6D","article-title":"Heme and iron metabolism: Role in cerebral hemorrhage","volume":"23","author":"Wagner","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1161\/hs1201.099820","article-title":"Mechanisms of edema formation after intracerebral hemorrhage: Effects of extravasated red blood cells on blood flow and blood-brain barrier integrity","volume":"32","author":"Xi","year":"2001","journal-title":"Stroke"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3171\/jns.1994.81.2.0261","article-title":"The role of hemolysate in the facilitation of oxyhemoglobin-induced contraction in rabbit basilar arteries","volume":"81","author":"Aoki","year":"1994","journal-title":"J. Neurosurg."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1161\/STROKEAHA.110.596718","article-title":"Molecular pathophysiology of cerebral hemorrhage: Secondary brain injury","volume":"42","author":"Aronowski","year":"2011","journal-title":"Stroke"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/3953\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:19:32Z","timestamp":1760030372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/3953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26093953"],"URL":"https:\/\/doi.org\/10.3390\/ijms26093953","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]}}}