title: Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats.
abstract: Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O₂, 2.5 atmosphere absolutes) 1 h daily for 5 days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl₂), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats.
authors.affiliation: Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Soejima
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Paul R
authors.initials: PR
authors.lastname: Krafft
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fujii
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control; D003035:Cobalt / Q000494:pharmacology; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000633:toxicity; D006454:Hemoglobins / Q000378:metabolism; D006931:Hyperbaric Oxygenation / Q000379:methods*; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013053:Spectrophotometry; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D016166:Free Radical Scavengers; D006454:Hemoglobins; D017382:Reactive Oxygen Species; D003035:Cobalt; D045726:Metalloproteases; C018021:cobaltous chloride; D005947:Glucose
keywords: Hemorrhagic transformation; Hyperbaric oxygen preconditioning; MCAO; MMP-2 and MMP-9
references.citation: Stroke. 2004 Nov;35(11 Suppl 1):2726-30
references.pmid: 15459442
references.citation: Exp Neurol. 2009 Mar;216(1):35-46
references.pmid: 19073180
references.citation: Transl Stroke Res. 2011 Sep 1;2(3):316-27
references.pmid: 23060945
references.citation: Arch Neurol. 2001 Aug;58(8):1209-12
references.pmid: 11493160
references.citation: Acta Neurochir Suppl. 2010;106:217-20
references.pmid: 19812952
references.citation: Lancet Neurol. 2009 Apr;8(4):398-412
references.pmid: 19296922
references.citation: EMBO J. 2012 May 30;31(11):2448-60
references.pmid: 22562152
references.citation: Mol Neurobiol. 2003 Dec;28(3):229-44
references.pmid: 14709787
references.citation: Med Gas Res. 2012 Apr 11;2(1):9
references.pmid: 22494892
references.citation: BMC Neurosci. 2005 Aug 03;6:49
references.pmid: 16078993
references.citation: Neurobiol Dis. 2008 Jan;29(1):1-13
references.pmid: 17822911
references.citation: N Engl J Med. 1996 Jun 20;334(25):1642-8
references.pmid: 8628361
references.citation: Antioxid Redox Signal. 2011 Sep 1;15(5):1305-23
references.pmid: 21294658
references.citation: J Cereb Blood Flow Metab. 2006 May;26(5):666-74
references.pmid: 16136055
references.citation: Transplant Rev (Orlando). 2012 Apr;26(2):115-24
references.pmid: 22000660
references.citation: Stroke. 1995 Apr;26(4):627-34; discussion 635
references.pmid: 7709410
references.citation: Transl Stroke Res. 2011 Sep;2(3):391-8
references.pmid: 21909340
references.citation: Transl Stroke Res. 2012 Jun;3(2):296-304
references.pmid: 23626658
references.citation: Cancer Metastasis Rev. 2010 Jun;29(2):285-93
references.pmid: 20393783
references.citation: Stroke. 2003 Sep;34(9):2215-20
references.pmid: 12907821
references.citation: Transl Stroke Res. 2010 Mar;1(1):2-3
references.pmid: 24323449
references.citation: Brain Res. 2008 May 30;1212:71-8
references.pmid: 18439571
references.citation: Eur J Appl Physiol. 2001 Nov;86(1):24-7
references.pmid: 11820317
references.citation: Acta Neurochir Suppl. 2008;105:191-6
references.pmid: 19066108
references.citation: Free Radic Biol Med. 2007 Nov 1;43(9):1219-25
references.pmid: 17893032
references.citation: Stroke. 2011 Jun;42(6):1750-6
references.pmid: 21474807
references.citation: J Appl Physiol (1985). 2009 Mar;106(3):988-95
references.pmid: 18845776