title: Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage.
abstract: We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.
authors.affiliation: 1 Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kuo-Chuan
authors.initials: KC
authors.lastname: Wang
authors.affiliation: 2 Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Tang
authors.affiliation: 3 Department of Neurology, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Jing-Er
authors.initials: JE
authors.lastname: Lee
authors.affiliation: 4 Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-I
authors.initials: YI
authors.lastname: Li
authors.affiliation: 5 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
authors.affiliation: 6 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.|7 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.affiliation: 2 Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Jiann-Shing
authors.initials: JS
authors.lastname: Jeng
authors.affiliation: 8 Department of Physiology, Yong Loo Lin School Medicine, National University of Singapore, Singapore.
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
authors.affiliation: 1 Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yong-Kwang
authors.initials: YK
authors.lastname: Tu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D002478:Cells, Cultured; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000134:cerebrospinal fluid* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011994:Recombinant Proteins
keywords: Cell death mechanisms; cerebrospinal fluid; inflammation; receptors; subarachnoid hemorrhage
references.citation: Acta Neurochir (Wien). 1993;123(1-2):25-32
references.pmid: 8213274
references.citation: Stroke. 2007 Aug;38(8):2315-21
references.pmid: 17569871
references.citation: Acta Neurochir Suppl. 2011;110(Pt 1):57-61
references.pmid: 21116915
references.citation: J Neuroimmunol. 2003 Mar;136(1-2):119-24
references.pmid: 12620650
references.citation: Brain Res. 2013 Jun 23;1517:133-40
references.pmid: 23603413
references.citation: Nat Rev Immunol. 2005 Apr;5(4):331-42
references.pmid: 15803152
references.citation: Mol Neurobiol. 2012 Jun;45(3):499-506
references.pmid: 22580958
references.citation: N Engl J Med. 2006 Aug 31;355(9):928-39
references.pmid: 16943405
references.citation: Neurocrit Care. 2009 Dec;11(3):362-8
references.pmid: 19777384
references.citation: Prog Neurobiol. 2014 Apr;115:64-91
references.pmid: 24076160
references.citation: J Neurol Neurosurg Psychiatry. 2013 May;84(5):517-22
references.pmid: 23255728
references.citation: Pharmacol Ther. 2014 Mar;141(3):347-57
references.pmid: 24220159
references.citation: J Neurochem. 2007 May;101(3):729-36
references.pmid: 17254011
references.citation: Acta Neurochir (Wien). 2013 Feb;155(2):255-60
references.pmid: 23180171
references.citation: J Neurosurg. 2014 Dec;121(6):1388-93
references.pmid: 25280089
references.citation: Acta Neurochir Suppl. 2013;115:57-61
references.pmid: 22890645
references.citation: J Clin Invest. 1999 Jul;104(1):59-66
references.pmid: 10393699
references.citation: Nat Rev Neurol. 2014 Jan;10(1):44-58
references.pmid: 24323051
references.citation: J Neurosci. 2008 Nov 12;28(46):12023-31
references.pmid: 19005067
references.citation: Stroke. 2011 May;42(5):1420-8
references.pmid: 21474801
references.citation: Free Radic Biol Med. 2000 Jan 15;28(2):289-309
references.pmid: 11281297
references.citation: Neuroscience. 2012 Dec 13;226:510-6
references.pmid: 23122444
references.citation: J Neuroinflammation. 2014 Jun 10;11:101
references.pmid: 24912490
references.citation: J Neurochem. 2007 Oct;103(2):590-603
references.pmid: 17666052
references.citation: J Cereb Blood Flow Metab. 2004 Aug;24(8):916-25
references.pmid: 15362722
references.citation: Transl Stroke Res. 2011 Mar 1;2(1):72-9
references.pmid: 21479116
references.citation: Neurosurgery. 2013 Oct;73(4):617-23; discussion 623
references.pmid: 23787882
references.citation: Free Radic Biol Med. 1997;22(6):1075-99
references.pmid: 9034247
references.citation: Neuroimmunomodulation. 2013;20(2):113-8
references.pmid: 23328212
references.citation: Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):585-94
references.pmid: 23288172
references.citation: Transl Stroke Res. 2013 Aug;4(4):432-46
references.pmid: 23894255
references.citation: Autoimmun Rev. 2012 Oct;11(12):909-17
references.pmid: 22495229
references.citation: Lancet. 1975 Mar 1;1(7905):480-4
references.pmid: 46957
references.citation: Stroke Res Treat. 2013;2013:394036
references.pmid: 23533958
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13798-803
references.pmid: 17693552
references.citation: Exp Neurol. 2013 Dec;250:341-7
references.pmid: 24196452
references.citation: J Surg Res. 2015 Dec;199(2):523-8
references.pmid: 26076684