title: Inflammatory responses in hypoxic ischemic encephalopathy.
abstract: Inflammation plays a critical role in mediating brain injury induced by neonatal hypoxic ischemic encephalopathy (HIE). The mechanisms underlying inflammatory responses to ischemia may be shared by neonatal and adult brains; however, HIE exhibits a unique inflammation phenotype that results from the immaturity of the neonatal immune system. This review will discuss the current knowledge concerning systemic and local inflammatory responses in the acute and subacute stages of HIE. The key components of inflammation, including immune cells, adhesion molecules, cytokines, chemokines and oxidative stress, will be reviewed, and the differences between neonatal and adult inflammatory responses to cerebral ischemic injury will also be discussed.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, USA. fliu@uchc.edu
authors.forename: Fudong
authors.initials: F
authors.lastname: Liu
authors.forename: Louise D
authors.initials: LD
authors.lastname: McCullough
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D016207:Cytokines
references.citation: Pediatr Res. 1994 Dec;36(6):699-706
references.pmid: 7898977
references.citation: J Neuroinflammation. 2013 Feb 07;10:24
references.pmid: 23390999
references.citation: Circ Res. 1997 Sep;81(3):304-10
references.pmid: 9285631
references.citation: Pediatr Res. 1996 Oct;40(4):603-9
references.pmid: 8888290
references.citation: J Reprod Immunol. 2011 Jun;90(1):74-81
references.pmid: 21641657
references.citation: J Nanosci Nanotechnol. 2005 Aug;5(8):1261-5
references.pmid: 16193989
references.citation: Acta Neurochir Suppl. 1997;70:1-3
references.pmid: 9416261
references.citation: Pediatr Res. 2004 Oct;56(4):656-62
references.pmid: 15295091
references.citation: Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H558-68
references.pmid: 15764676
references.citation: Neurobiol Dis. 2008 Jul;31(1):133-44
references.pmid: 18571099
references.citation: Eur J Pharmacol. 1998 Jan 19;342(1):47-9
references.pmid: 9544791
references.citation: Curr Top Med Chem. 2006;6(10):929-34
references.pmid: 16787266
references.citation: Glia. 1993 Jan;7(1):19-24
references.pmid: 7678581
references.citation: Dev Neurosci. 2005 Mar-Aug;27(2-4):143-8
references.pmid: 16046848
references.citation: Pediatr Res. 2010 Jul;68(1):41-7
references.pmid: 20351655
references.citation: J Bioenerg Biomembr. 2004 Aug;36(4):329-33
references.pmid: 15377867
references.citation: J Leukoc Biol. 2010 May;87(5):779-89
references.pmid: 20130219
references.citation: Acta Neuropathol. 1986;70(3-4):302-7
references.pmid: 3532687
references.citation: Blood. 2010 Aug 5;116(5):841-9
references.pmid: 20407037
references.citation: Eur J Pediatr. 1997 Dec;156(12):944-8
references.pmid: 9453378
references.citation: Neuropathol Appl Neurobiol. 1994 Apr;20(2):144-51
references.pmid: 8072645
references.citation: J Trop Pediatr. 2010 Jun;56(3):178-82
references.pmid: 19822562
references.citation: Acta Neurochir Suppl. 1996;66:27-31
references.pmid: 8780793
references.citation: J Cereb Blood Flow Metab. 1998 Dec;18(12):1336-45
references.pmid: 9850146
references.citation: Clin Appl Thromb Hemost. 2009 Oct;15(5):545-51
references.pmid: 18591180
references.citation: Brain Res Mol Brain Res. 1998 Apr;55(2):306-14
references.pmid: 9582443
references.citation: Glia. 2000 Oct;32(1):1-14
references.pmid: 10975906
references.citation: Prog Neurobiol. 1999 Jun;58(3):233-47
references.pmid: 10341362
references.citation: J Cereb Blood Flow Metab. 2005 Sep;25(9):1138-49
references.pmid: 15874975
references.citation: Nat Neurosci. 2007 Dec;10(12):1544-53
references.pmid: 18026096
references.citation: Fed Proc. 1987 May 15;46(7):2397-401
references.pmid: 3552737
references.citation: Ann Neurol. 2000 Jan;47(1):54-63
references.pmid: 10632101
references.citation: J Neuroinflammation. 2013 Jan 24;10:13
references.pmid: 23347579
references.citation: J Neuroimmune Pharmacol. 2013 Mar;8(1):66-78
references.pmid: 22367679
references.citation: Neurology. 2001 Oct 23;57(8):1428-34
references.pmid: 11673584
references.citation: Am J Pathol. 1994 Sep;145(3):728-40
references.pmid: 8080052
references.citation: Blood. 1996 May 1;87(9):3929-33
references.pmid: 8611722
references.citation: J Neurosci. 2008 Nov 5;28(45):11650-61
references.pmid: 18987201
references.citation: Stroke. 2003 Nov;34(11):2543-8
references.pmid: 14563972
references.citation: Neurochem Res. 2003 Feb;28(2):215-23
references.pmid: 12608695
references.citation: J Cereb Blood Flow Metab. 1995 Nov;15(6):941-7
references.pmid: 7593354
references.citation: Brain Res Dev Brain Res. 1995 Feb 16;84(2):245-52
references.pmid: 7743644
references.citation: J Immunol. 1991 May 15;146(10):3372-9
references.pmid: 1709192
references.citation: Cardiovasc Res. 2005 Jan 1;65(1):16-27
references.pmid: 15621030
references.citation: J Comp Neurol. 1999 Mar 22;405(4):553-62
references.pmid: 10098945
references.citation: Curr Pharm Des. 2008;14(16):1625-43
references.pmid: 18673205
references.citation: Brain Pathol. 2000 Jan;10(1):95-112
references.pmid: 10668900
references.citation: Stroke. 1991 Apr;22(4):516-21
references.pmid: 2024281
references.citation: Pediatr Res. 1996 Jan;39(1):39-47
references.pmid: 8825384
references.citation: Nat Med. 2011 Jul 07;17(7):796-808
references.pmid: 21738161
references.citation: Exp Neurol. 2000 Oct;165(2):295-305
references.pmid: 10993690
references.citation: Glia. 1996 Dec;18(4):319-31
references.pmid: 8972800
references.citation: BMC Neurosci. 2005 Oct 31;6:63
references.pmid: 16259636
references.citation: Stroke. 2000 Jul;31(7):1752-61
references.pmid: 10884483
references.citation: Stroke. 1991 Jul;22(7):877-83
references.pmid: 1677219
references.citation: Circulation. 2006 May 2;113(17):2105-12
references.pmid: 16636173
references.citation: Cytokine. 2008 Jul;43(1):54-62
references.pmid: 18511291
references.citation: Adv Exp Med Biol. 2002;513:87-113
references.pmid: 12575818
references.citation: Eur J Neurosci. 2001 Nov;14(10):1651-8
references.pmid: 11860459
references.citation: Stroke. 2012 Nov;43(11):3063-70
references.pmid: 22933588
references.citation: Neurol Res. 1996 Apr;18(2):171-5
references.pmid: 9162874
references.citation: Pediatr Res. 2006 May;59(5):680-3
references.pmid: 16627881
references.citation: Neurochem Res. 2004 Mar;29(3):601-8
references.pmid: 15038607
references.citation: Curr Mol Med. 2004 Mar;4(2):193-205
references.pmid: 15032713
references.citation: Pediatr Res. 2004 Sep;56(3):377-84
references.pmid: 15201401
references.citation: Clin Exp Immunol. 1995 Jul;101(1):183-9
references.pmid: 7542575
references.citation: Brain Res. 1998 Mar 30;788(1-2):25-34
references.pmid: 9554941
references.citation: J Neurol Sci. 1996 May;137(2):69-78
references.pmid: 8782158
references.citation: Neurotherapeutics. 2010 Oct;7(4):378-91
references.pmid: 20880502
references.citation: Neurol Res. 2004 Dec;26(8):884-92
references.pmid: 15727272
references.citation: Clin Neurosci Res. 2006 Dec 1;6(5):293-313
references.pmid: 20300490
references.citation: Eur J Immunol. 1998 Oct;28(10):3086-99
references.pmid: 9808177
references.citation: Pediatr Res. 2005 Aug;58(2):199-205
references.pmid: 16006432
references.citation: Stroke. 1995 Jun;26(6):1093-100
references.pmid: 7762028
references.citation: Brain Res Dev Brain Res. 2003 Mar 14;141(1-2):25-32
references.pmid: 12644245
references.citation: Arch Immunol Ther Exp (Warsz). 2012 Aug;60(4):251-66
references.pmid: 22710659
references.citation: Prog Neurobiol. 1998 Oct;56(2):149-71
references.pmid: 9760699
references.citation: Early Hum Dev. 2012 Dec;88(12):931-6
references.pmid: 23078831
references.citation: J Neuroinflammation. 2008 Sep 22;5:39
references.pmid: 18808689
references.citation: Apoptosis. 1997;2(4):368-76
references.pmid: 14646533
references.citation: Pediatr Res. 2002 Jun;51(6):768-76
references.pmid: 12032276
references.citation: Curr Med Res Opin. 2002;18 Suppl 2:s18-22
references.pmid: 12365824
references.citation: Curr Opin Investig Drugs. 2003 May;4(5):522-9
references.pmid: 12833644
references.citation: J Cereb Blood Flow Metab. 2001 Sep;21(9):1115-24
references.pmid: 11524616
references.citation: J Neurosci. 2004 Feb 11;24(6):1350-7
references.pmid: 14960606
references.citation: Stroke. 1995 Aug;26(8):1438-42; discussion 1443
references.pmid: 7631350
references.citation: J Exp Med. 1995 Feb 1;181(2):669-75
references.pmid: 7530761
references.citation: N Engl J Med. 2006 Mar 2;354(9):899-910
references.pmid: 16510744
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):18150-5
references.pmid: 23071306
references.citation: Brain Res. 2005 Dec 20;1066(1-2):49-56
references.pmid: 16336947
references.citation: Semin Neonatol. 2000 Feb;5(1):3-16
references.pmid: 10802746
references.citation: Stroke. 2002 Sep;33(9):2304-10
references.pmid: 12215603
references.citation: JAMA Neurol. 2013 Feb;70(2):172-82
references.pmid: 23128399
references.citation: J Neurosci Res. 1991 Jul;29(3):336-45
references.pmid: 1656059
references.citation: J Clin Invest. 1996 Jan 1;97(1):209-16
references.pmid: 8550836
references.citation: Pediatr Res. 1994 Dec;36(6):799-804
references.pmid: 7534904
references.citation: Leg Med (Tokyo). 2003 Mar;5 Suppl 1:S45-57
references.pmid: 12935551
references.citation: Pediatr Res. 1996 Jul;40(1):6-14
references.pmid: 8798238
references.citation: Exp Neurol. 1994 Dec;130(2):362-7
references.pmid: 7867766
references.citation: Ann Neurol. 2011 Oct;70(4):550-65
references.pmid: 21796662
references.citation: J Neurosci. 2001 Mar 15;21(6):1931-8
references.pmid: 11245678
references.citation: Ann Neurol. 1994 Apr;35(4):458-63
references.pmid: 8154873
references.citation: Stroke. 2002 Mar;33(3):795-801
references.pmid: 11872906
references.citation: Thromb Haemost. 2011 Mar;105(3):409-20
references.pmid: 21174009
references.citation: J Neurochem. 2012 Mar;120(6):964-73
references.pmid: 22192001
references.citation: J Neuropathol Exp Neurol. 2004 Jan;63(1):84-96
references.pmid: 14748564
references.citation: Neuroscience. 2003;121(3):619-28
references.pmid: 14568022
references.citation: Neurol Res. 2012 May;34(4):338-45
references.pmid: 22643077
references.citation: J Clin Invest. 1981 Oct;68(4):863-74
references.pmid: 7287906
references.citation: Blood. 1999 Jul 15;94(2):600-9
references.pmid: 10397727
references.citation: J Cereb Blood Flow Metab. 2010 Jul;30(7):1306-17
references.pmid: 20145655
references.citation: J Neurochem. 2012 Nov;123 Suppl 2:148-55
references.pmid: 23050652
references.citation: Am J Respir Cell Mol Biol. 1991 Mar;4(3):195-203
references.pmid: 2001288
references.citation: N Engl J Med. 2012 May 17;366(20):1870-80
references.pmid: 22591293
references.citation: J Neuroinflammation. 2011 Dec 10;8:174
references.pmid: 22152337
references.citation: Pediatr Res. 1997 May;41(5):607-16
references.pmid: 9128280
references.citation: J Cereb Blood Flow Metab. 2006 May;26(5):654-65
references.pmid: 16121126
references.citation: Immunol Cell Biol. 2008 Jul;86(5):398-408
references.pmid: 18392044
references.citation: Neurology. 1995 Apr;45(4):815-9
references.pmid: 7723976
references.citation: Pediatr Res. 1999 Apr;45(4 Pt 1):500-9
references.pmid: 10203141
references.citation: Curr Pharm Des. 2008;14(33):3574-89
references.pmid: 19075734
references.citation: Neuroscience. 2000;101(3):737-44
references.pmid: 11113322
references.citation: Stroke. 1992 Sep;23(9):1367-79
references.pmid: 1519296
references.citation: Pediatr Res. 2003 Jan;53(1):132-6
references.pmid: 12508092
references.citation: Science. 2003 Dec 5;302(5651):1760-5
references.pmid: 14615545
references.citation: J Child Neurol. 2009 Sep;24(9):1119-26
references.pmid: 19605775
references.citation: Free Radic Res. 2009 Apr;43(4):348-64
references.pmid: 19241241
references.citation: Am J Pathol. 1994 Jan;144(1):188-99
references.pmid: 8291608
references.citation: Pediatr Res. 2000 Jan;47(1):79-83
references.pmid: 10625086
references.citation: Ann Neurol. 1995 Dec;38(6):935-42
references.pmid: 8526467
references.citation: J Intern Med. 2001 Aug;250(2):91-104
references.pmid: 11489059
references.citation: Am J Obstet Gynecol. 1998 Jul;179(1):194-202
references.pmid: 9704787
references.citation: J Neuropathol Exp Neurol. 2003 Feb;62(2):127-36
references.pmid: 12578222
references.citation: Nat Rev Immunol. 2007 Sep;7(9):678-89
references.pmid: 17717539
references.citation: Nat Neurosci. 2005 Jun;8(6):752-8
references.pmid: 15895084
references.citation: J Immunol. 2003 Nov 1;171(9):4700-7
references.pmid: 14568945
references.citation: Dev Neurosci. 2005 Mar-Aug;27(2-4):100-11
references.pmid: 16046843
references.citation: Neurosci Lett. 1999 Mar 19;263(1):72-6
references.pmid: 10218914
references.citation: Am J Obstet Gynecol. 1998 Jan;178(1 Pt 1):24-32
references.pmid: 9465798
references.citation: Am J Pathol. 2008 Jan;172(1):1-7
references.pmid: 18079440
references.citation: Br J Pharmacol. 2012 Jun;166(4):1211-24
references.pmid: 22352897
references.citation: Brain Behav Immun. 2012 Nov;26(8):1331-9
references.pmid: 22982341
references.citation: Stroke. 1986 Mar-Apr;17(2):246-53
references.pmid: 3961835
references.citation: Arch Dis Child. 1993 May;68(5 Spec No):561-5
references.pmid: 7686738
references.citation: Am J Pathol. 1996 Jan;148(1):241-8
references.pmid: 8546211
references.citation: J Leukoc Biol. 2008 Aug;84(2):477-9
references.pmid: 18495784
references.citation: J Cereb Blood Flow Metab. 1995 Jan;15(1):42-51
references.pmid: 7528223
references.citation: J Biomed Biotechnol. 2011;2011:609813
references.pmid: 21197402
references.citation: J Neurochem. 2007 Feb;100(4):893-904
references.pmid: 17212701
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
references.pmid: 23401516
references.citation: J Neurosci. 2002 Jul 15;22(14):5910-9
references.pmid: 12122053
references.citation: Mol Cell Neurosci. 2012 Mar;49(3):311-21
references.pmid: 22270046
references.citation: J Obstet Gynaecol Res. 2005 Apr;31(2):185-91
references.pmid: 15771647
references.citation: Dev Med Child Neurol. 1992 Nov;34(11):1010-4
references.pmid: 1358734
references.citation: Neurochem Int. 1997 Apr-May;30(4-5):375-83
references.pmid: 9106251
references.citation: Stroke. 1999 Sep;30(9):1916-23; discussion 1923-4
references.pmid: 10471445
references.citation: Mol Psychiatry. 2000 May;5(3):230-2
references.pmid: 10889520
references.citation: J Neurotrauma. 2001 Mar;18(3):351-9
references.pmid: 11284554
references.citation: Pediatrics. 1997 Dec;100(6):1004-14
references.pmid: 9374573
references.citation: Pediatr Res. 2004 Aug;56(2):219-26
references.pmid: 15181184
references.citation: Blood. 1990 Dec 15;76(12):2613-21
references.pmid: 1979926
references.citation: Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H636-44
references.pmid: 11788413
references.citation: Science. 2005 May 27;308(5726):1314-8
references.pmid: 15831717
references.citation: Clin Immunol Immunopathol. 1997 Jul;84(1):56-64
references.pmid: 9191884
references.citation: Biol Neonate. 2001;79(3-4):224-7
references.pmid: 11275656
references.citation: Pediatr Int. 2006 Feb;48(1):22-8
references.pmid: 16490065
references.citation: Ann N Y Acad Sci. 1998 Sep 29;856:62-8
references.pmid: 9917865
references.citation: J Neurol Sci. 1994 Aug;125(1):3-10
references.pmid: 7964886
references.citation: N Engl J Med. 2004 Nov 4;351(19):1985-95
references.pmid: 15525724
references.citation: J Neurol Neurosurg Psychiatry. 1969 Oct;32(5):404-13
references.pmid: 5360048
references.citation: Stroke. 1994 Jul;25(7):1469-75
references.pmid: 8023364
references.citation: Neurochem Int. 2000 Apr;36(4-5):291-300
references.pmid: 10732996
references.citation: World J Pediatr. 2008 May;4(2):140-4
references.pmid: 18661772
references.citation: Pediatr Res. 2004 Apr;55(4):549-56
references.pmid: 14739365