title: Oxidative mechanisms of brain dysfunction during sepsis.
abstract: Oxidative stress has drawn a lot of attention in the past few decades, since it has been reported to participate in the mechanism of many diseases. Therefore, it seemed to be a good rationale to aim oxidative stress on therapeutic research. Sepsis is a complex systemic syndrome characterized by an imbalance between pro- and anti-inflammatory responses to a pathogen; its pathophysiology is a dynamic process which involves components of the immune system, the coagulation pathway, parenchymal cells, and the endocrine and metabolic pathways. It is well characterized that oxidative stress plays a crucial role in sepsis development, but the relation between central nervous system dysfunction and oxidative stress during sepsis is not well understood. Thus, we here summarize the current knowledge on the role of free radicals in the development of brain dysfunction in sepsis focusing on oxidative damage and the redox control of brain inflammatory pathways.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: Cristiane
authors.initials: C
authors.lastname: Ritter
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Cassol
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Fabrícia
authors.initials: F
authors.lastname: Petronilho
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Zugno
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction
references.citation: Kidney Int. 2007 Sep;72(5):557-65
references.pmid: 17538569
references.citation: Arch Surg. 1989 Dec;124(12):1386-9
references.pmid: 2589962
references.citation: Ann N Y Acad Sci. 2002 Apr;959:263-74
references.pmid: 11976201
references.citation: Clin Sci (Lond). 1999 May;96(5):461-6
references.pmid: 10209077
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11393-7
references.pmid: 7972071
references.citation: Crit Care Med. 1993 Jan;21(1):98-103
references.pmid: 8420739
references.citation: Physiol Res. 2006;55(1):33-8
references.pmid: 15857166
references.citation: Blood. 1999 Mar 1;93(5):1464-76
references.pmid: 10029572
references.citation: J Neurosci. 2005 Apr 20;25(16):4082-90
references.pmid: 15843610
references.citation: Biochim Biophys Acta. 2006 Apr;1757(4):262-72
references.pmid: 16626626
references.citation: Arch Surg. 1986 Feb;121(2):196-208
references.pmid: 3484944
references.citation: J Hypertens. 1999 Sep;17(9):1249-56
references.pmid: 10489101
references.citation: Lab Invest. 2007 Dec;87(12):1186-94
references.pmid: 17922019
references.citation: Clin Invest Med. 1990 Dec;13(6):297-304
references.pmid: 2078909
references.citation: Biochemistry (Mosc). 2005 Feb;70(2):200-14
references.pmid: 15807660
references.citation: Neuroendocrinology. 1998 Feb;67(2):109-16
references.pmid: 9508041
references.citation: J Pharmacol Exp Ther. 2006 Apr;317(1):181-7
references.pmid: 16368897
references.citation: Mol Cell Biol. 1994 Jul;14(7):4443-54
references.pmid: 8007951
references.citation: Brain Res. 1999 Mar 13;821(2):322-32
references.pmid: 10064818
references.citation: Free Radic Biol Med. 2004 Aug 15;37(4):433-41
references.pmid: 15256215
references.citation: J Neurochem. 2001 Nov;79(3):648-57
references.pmid: 11701768
references.citation: Intensive Care Med. 2004 Nov;30(11):2009-16
references.pmid: 15372146
references.citation: Exp Neurol. 2008 Sep;213(1):114-21
references.pmid: 18586243
references.citation: Am J Respir Crit Care Med. 2001 May;163(6):1389-94
references.pmid: 11371406
references.citation: Neurol Res. 1998 Mar;20(2):100-6
references.pmid: 9522343
references.citation: Ann Trop Paediatr. 2000 Mar;20(1):27-33
references.pmid: 10824210
references.citation: Neurosci Lett. 2005 Mar 16;376(3):171-6
references.pmid: 15721216
references.citation: Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):716-22
references.pmid: 10934111
references.citation: Proc Soc Exp Biol Med. 1987 Jun;185(2):206-10
references.pmid: 3554261
references.citation: Crit Care. 2005 Apr;9(2):145-6
references.pmid: 15774066
references.citation: Crit Care. 2005 Apr;9(2):R96-109
references.pmid: 15774056
references.citation: Curr Pharm Des. 2006;12(32):4123-34
references.pmid: 17100615
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1610-5
references.pmid: 11818564
references.citation: Intensive Care Med. 2003 Oct;29(10):1782-9
references.pmid: 12783160
references.citation: Neurology. 2002 Jan 22;58(2):186-91
references.pmid: 11805243
references.citation: Crit Care. 2006;10(6):238
references.pmid: 17118217
references.citation: Arch Biochem Biophys. 1985 Mar;237(2):408-14
references.pmid: 2983613
references.citation: Exp Mol Med. 2007 Aug 31;39(4):421-38
references.pmid: 17934330
references.citation: Br J Pharmacol. 2005 Jun;145(4):460-8
references.pmid: 15806113
references.citation: Brain Pathol. 2004 Jan;14(1):21-33
references.pmid: 14997934
references.citation: Internist (Berl). 1998 May;39(5):485-92
references.pmid: 9647983
references.citation: Neurochem Int. 1999 Feb;34(2):91-9
references.pmid: 10213066
references.citation: Exp Neurol. 2002 Jul;176(1):175-82
references.pmid: 12093094
references.citation: Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):113-85
references.pmid: 17562450
references.citation: Int J Biochem Cell Biol. 2005 Dec;37(12):2478-503
references.pmid: 16103002
references.citation: Am J Respir Crit Care Med. 2000 Jun;161(6):1907-11
references.pmid: 10852765
references.citation: Am Surg. 1997 Jan;63(1):20-3
references.pmid: 8985066
references.citation: N Engl J Med. 2003 Jan 9;348(2):138-50
references.pmid: 12519925
references.citation: J Alzheimers Dis. 2003 Apr;5(2):105-17
references.pmid: 12719628
references.citation: Intensive Care Med. 2004 Nov;30(11):1997-2008
references.pmid: 15549252
references.citation: Brain Res Brain Res Rev. 1999 Aug;30(2):153-63
references.pmid: 10525172
references.citation: J Neurosci. 2001 Sep 1;21(17):6480-91
references.pmid: 11517237
references.citation: J Neurochem. 2000 May;74(5):1989-98
references.pmid: 10800942
references.citation: Exp Physiol. 2007 Sep;92(5):807-11
references.pmid: 17675415
references.citation: FASEB J. 2002 Nov;16(13):1713-20
references.pmid: 12409313
references.citation: Annu Rev Immunol. 1997;15:351-69
references.pmid: 9143692
references.citation: J Clin Invest. 1995 Mar;95(3):1086-91
references.pmid: 7883956
references.citation: Glia. 1996 Feb;16(2):165-73
references.pmid: 8929903
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):9010-4
references.pmid: 12060716
references.citation: Am J Pathol. 1993 Apr;142(4):1265-78
references.pmid: 8475997
references.citation: Crit Care Med. 2008 Jun;36(6):1925-32
references.pmid: 18496362
references.citation: Free Radic Biol Med. 2003 Mar 15;34(6):766-73
references.pmid: 12633753
references.citation: Life Sci. 2008 May 23;82(21-22):1111-6
references.pmid: 18452953
references.citation: Neurochem Res. 2005 Jun-Jul;30(6-7):791-6
references.pmid: 16187214
references.citation: J Neuroinflammation. 2008 Sep 15;5:38
references.pmid: 18793399
references.citation: Cell. 2005 Jun 3;121(5):667-70
references.pmid: 15935753
references.citation: Adv Exp Med Biol. 2003;530:725-36
references.pmid: 14562771
references.citation: Nucleic Acids Res. 1999 Aug 1;27(15):3213-8
references.pmid: 10454620
references.citation: Nat Med. 1996 May;2(5):581-4
references.pmid: 8616720
references.citation: Anesthesiology. 2006 Oct;105(4):819-37
references.pmid: 17006082
references.citation: Brain Res. 1992 Aug 7;587(2):250-6
references.pmid: 1381982
references.citation: Cell Metab. 2005 Jun;1(6):401-8
references.pmid: 16054089
references.citation: Anesth Analg. 2001 Mar;92(3):681-7
references.pmid: 11226101
references.citation: Shock. 2004 May;21(5):458-65
references.pmid: 15087823
references.citation: Glia. 2000 Jan 1;29(1):1-13
references.pmid: 10594918
references.citation: J Endocrinol. 2003 Jul;178(1):5-12
references.pmid: 12844330
references.citation: Crit Care Med. 2007 Sep;35(9):2233-4
references.pmid: 17713382
references.citation: J Clin Invest. 1996 Jan 1;97(1):209-16
references.pmid: 8550836
references.citation: Crit Care Med. 1991 May;19(5):732-5
references.pmid: 2026037
references.citation: J Neurosci. 1999 May 15;19(10):3809-17
references.pmid: 10234013
references.citation: J Neurochem. 2006 Jun;97(6):1634-58
references.pmid: 16805774
references.citation: Brain Res. 2004 Sep 17;1021(1):20-31
references.pmid: 15328028
references.citation: Am J Respir Crit Care Med. 1998 Feb;157(2):421-7
references.pmid: 9476853
references.citation: Ann N Y Acad Sci. 2000;899:136-47
references.pmid: 10863535
references.citation: Nature. 1954 Oct 9;174(4432):689-91
references.pmid: 13213980
references.citation: Crit Care. 2004 Apr;8(2):R91-8
references.pmid: 15025783
references.citation: J Mol Cell Cardiol. 2001 Jun;33(6):1065-89
references.pmid: 11444914
references.citation: Am Surg. 1993 Jan;59(1):9-12
references.pmid: 8480936
references.citation: Crit Care Med. 2005 Dec;33(12 Suppl):S498-501
references.pmid: 16340433
references.citation: Biosci Rep. 1997 Feb;17(1):3-8
references.pmid: 9171915
references.citation: Intensive Care Med. 2000 Apr;26(4):474-6
references.pmid: 10872143
references.citation: Mitochondrion. 2008 Sep;8(4):313-8
references.pmid: 18657632
references.citation: Biochem J. 1980 Nov 1;191(2):421-7
references.pmid: 6263247
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7534-9
references.pmid: 18490655
references.citation: Free Radic Res. 2003 Jan;37(1):19-27
references.pmid: 12653213
references.citation: Neuroscience. 2006 Jul 21;140(4):1157-68
references.pmid: 16713109
references.citation: Mol Cell Biochem. 2003 May;247(1-2):83-94
references.pmid: 12841635
references.citation: Am J Emerg Med. 1991 Mar;9(2):139-43
references.pmid: 1994941
references.citation: J Surg Res. 1985 Mar;38(3):267-71
references.pmid: 2858604
references.citation: Ann Neurol. 1996 Mar;39(3):385-9
references.pmid: 8602759
references.citation: J Surg Res. 2007 Aug;141(2):252-6
references.pmid: 17490683
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13798-803
references.pmid: 17693552
references.citation: Ann Neurol. 2005 Oct;58(4):495-505
references.pmid: 16178023
references.citation: Exp Mol Med. 2007 Dec 31;39(6):812-9
references.pmid: 18160852
references.citation: Crit Care Med. 1989 May;17(5):399-403
references.pmid: 2495896
references.citation: Free Radic Res. 2006 Jul;40(7):685-95
references.pmid: 16983995
references.citation: Intensive Care Med. 2007 Jun;33(6):941-50
references.pmid: 17410344
references.citation: Free Radic Biol Med. 2007 Jan 15;42(2):153-64
references.pmid: 17189821
references.citation: Neuroimmunomodulation. 2005;12(5):255-69
references.pmid: 16166805
references.citation: FASEB J. 2000 Oct;14(13):1889-900
references.pmid: 11023973
references.citation: Gen Pharmacol. 1997 Aug;29(2):159-66
references.pmid: 9251894
references.citation: Cardiovasc Res. 1999 Mar;41(3):511-3
references.pmid: 10435022
references.citation: Am J Respir Crit Care Med. 1999 Jul;160(1):50-6
references.pmid: 10390379
references.citation: J Neurochem. 2000 Oct;75(4):1455-64
references.pmid: 10987825
references.citation: Biochim Biophys Acta. 1988 Dec 7;936(3):377-85
references.pmid: 2848580
references.citation: Intensive Care Med. 1990;16 Suppl 3:S192-6
references.pmid: 2289989
references.citation: Eur J Pharmacol. 2008 Jun 24;588(1):106-13
references.pmid: 18499097
references.citation: Crit Care Med. 2006 Mar;34(3):886-9
references.pmid: 16505668
references.citation: J Biol Chem. 2002 Aug 16;277(33):29584-92
references.pmid: 12048217
references.citation: Mol Aspects Med. 2004 Feb-Apr;25(1-2):125-39
references.pmid: 15051322
references.citation: Surgery. 1994 Nov;116(5):859-67
references.pmid: 7940190
references.citation: Fundam Clin Pharmacol. 2008 Apr;22(2):203-9
references.pmid: 18353115
references.citation: Int Arch Allergy Immunol. 1997 Dec;114(4):336-42
references.pmid: 9414136
references.citation: Mol Cell Biol. 2007 Jan;27(2):411-25
references.pmid: 17074805
references.citation: Clinics (Sao Paulo). 2006 Feb;61(1):71-6
references.pmid: 16532228
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Mar;286(3):R491-7
references.pmid: 14604843
references.citation: Lancet. 2003 Nov 29;362(9398):1799-805
references.pmid: 14654318
references.citation: Crit Care Med. 2000 Nov;28(11):3599-605
references.pmid: 11098960
references.citation: Crit Care. 2005 Feb;9(1):37-44
references.pmid: 15693982
references.citation: Am J Physiol. 1999 Dec;277(6):H2240-6
references.pmid: 10600842
references.citation: Crit Care Med. 2000 Aug;28(8):3019-24
references.pmid: 10966289
references.citation: Am J Respir Crit Care Med. 2005 Feb 15;171(4):340-7
references.pmid: 15542793
references.citation: Mol Med. 1997 Nov;3(11):750-64
references.pmid: 9407551
references.citation: J Alzheimers Dis. 2005 Mar;8(4):369-75
references.pmid: 16556968
references.citation: Chem Biol Interact. 2006 Nov 7;163(3):207-17
references.pmid: 16982041
references.citation: Neurol Res. 1997 Aug;19(4):369-76
references.pmid: 9263215
references.citation: J Neurochem. 2008 Jul;106(2):770-80
references.pmid: 18419763
references.citation: Can J Neurol Sci. 2003 May;30(2):98-105
references.pmid: 12774948
references.citation: Trends Neurosci. 2000 Apr;23(4):175-80
references.pmid: 10717677
references.citation: Antioxid Redox Signal. 2005 May-Jun;7(5-6):829-34
references.pmid: 15890031
references.citation: Crit Care Med. 1999 Dec;27(12):2656-61
references.pmid: 10628605
references.citation: Prog Neurobiol. 2002 Jun;67(2):161-72
references.pmid: 12126659
references.citation: J Biol Chem. 2003 Sep 19;278(38):36027-31
references.pmid: 12840017
references.citation: J Neurochem. 1998 Jul;71(1):88-94
references.pmid: 9648854
references.citation: Glia. 2005 May;50(3):235-46
references.pmid: 15739188
references.citation: Annu Rev Biochem. 1995;64:97-112
references.pmid: 7574505
references.citation: Psychol Med. 1999 Mar;29(2):291-7
references.pmid: 10218921
references.citation: J Neurosci. 1998 Mar 1;18(5):1633-41
references.pmid: 9464988
references.citation: Br J Pharmacol. 1999 May;127(2):482-8
references.pmid: 10385249
references.citation: J Neuropathol Exp Neurol. 2001 Aug;60(8):759-67
references.pmid: 11487050
references.citation: Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):238-46
references.pmid: 9387883
references.citation: J Infect Dis. 1994 Aug;170(2):457-60
references.pmid: 8035037
references.citation: Crit Care Med. 1990 Aug;18(8):801-6
references.pmid: 2379391
references.citation: Trends Biochem Sci. 2005 Aug;30(8):453-61
references.pmid: 15996871
references.citation: Neuron. 2006 Jan 5;49(1):67-79
references.pmid: 16387640
references.citation: Biochemistry. 2003 Apr 22;42(15):4520-6
references.pmid: 12693948
references.citation: Glia. 2008 Jul;56(9):1028-37
references.pmid: 18381655
references.citation: J Immunol. 1992 Oct 15;149(8):2736-41
references.pmid: 1383325
references.citation: J Neurochem. 2007 Aug;102(3):667-78
references.pmid: 17403137
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28
references.pmid: 11076791
references.citation: J Immunol. 2008 Jul 1;181(1):680-9
references.pmid: 18566435
references.citation: Curr Infect Dis Rep. 2003 Oct;5(5):365-371
references.pmid: 13678565
references.citation: J Biol Chem. 2002 Aug 16;277(33):29626-33
references.pmid: 12050154
references.citation: Glia. 2005 Jun;50(4):329-39
references.pmid: 15846802
references.citation: Nature. 1990 Oct 25;347(6295):768-70
references.pmid: 1700301
references.citation: Behav Brain Res. 2006 Jul 15;171(1):94-108
references.pmid: 16677721
references.citation: Crit Care Med. 2005 Jan;33(1):221-3; discussion 262-3
references.pmid: 15644673
references.citation: J Neurochem. 2006 Sep;98(6):1852-65
references.pmid: 16945104
references.citation: J Neurochem. 2002 Jan;80(1):73-80
references.pmid: 11796745
references.citation: J Pharmacol Exp Ther. 2003 Jan;304(1):1-7
references.pmid: 12490568
references.citation: Crit Care Med. 1997 Oct;25(10):1700-6
references.pmid: 9377885
references.citation: Science. 1999 Mar 5;283(5407):1488-93
references.pmid: 10066163