Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage.
The CD4+CD25+regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model. Tregs treatment reduced the content of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and malondialdehyde, while increasing the superoxide dismutase (SOD) enzymatic activity at day (1, 3 and 7) following ICH. Furthermore, Tregs treatment obviously reduced the number of NF-κB+, IL-6+, TUNEL+and active caspase-3+cells at day 3 after ICH. These results indicate that adoptive transfer of Tregs may provide neuroprotection following ICH in mouse models.
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.
Lei-Lei
LL
Mao
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.|Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, 271016, Shandong, China.
Hui
H
Yuan
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.
Wen-Wen
WW
Wang
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.
Yu-Jing
YJ
Wang
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.
Ming-Feng
MF
Yang
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.|Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, 271016, Shandong, China.
Bao-Liang
BL
Sun
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China. zongyongzhanghust@163.com.
Zong-Yong
ZY
Zhang
Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China. xyyang@tsmc.edu.cn.
Xiao-Yi
XY
Yang
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006406:Hematoma / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D013482:Superoxide Dismutase / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism
D016207:Cytokines; D051996:Transcription Factor RelA; D008315:Malondialdehyde; D013482:Superoxide Dismutase
Intracerebral hemorrhage; Neurological deficits; Pro-inflammatory cytokines; Regulatory T cells
Transl Stroke Res. 2015 Feb;6(1):4-8
25533878
Nat Immunol. 2010 Jan;11(1):7-13
20016504
Lancet Neurol. 2012 Aug;11(8):720-31
22698888
Transl Stroke Res. 2016 Aug;7(4):313-21
27030356
Brain Res. 2009 Nov 17;1298:13-23
19728990
J Neurochem. 2007 May;101(3):652-63
17250675
Neurosci Lett. 2015 Mar 30;591:115-120
25703227
Prog Neurobiol. 2014 Apr;115:25-44
24291544
Neurosurgery. 2006 Mar;58(3):542-50; discussion 542-50
16528196
Clin Dev Immunol. 2013;2013:746068
24223607
Ann Neurol. 2013 Sep;74(3):458-71
23674483
Crit Care Med. 2016 Apr;44(4):790-7
26757167
Behav Brain Res. 2014 May 1;264:151-60
24518201
J Neuroinflammation. 2012 Mar 06;9:46
22394415
Cerebrovasc Dis. 2011;31(3):211-22
21178344
Nat Rev Immunol. 2008 Jul;8(7):523-32
18566595
Acta Neuropathol. 2009 Aug;118(2):197-217
19404652
Mol Neurobiol. 2017 Jan;54(1):1-14
26708209
Oxid Med Cell Longev. 2016;2016:1203285
27190572
Nanotechnology. 2016 Apr 29;27(17):175101
26965041
Nat Med. 2009 Feb;15(2):192-9
19169263
Stroke. 2013 Dec;44(12):3509-15
24092548
Int Immunopharmacol. 2014 Oct;22(2):522-5
25000335
J Neurosurg. 2000 Jan;92(1):108-20
10616089
Stroke. 1999 Nov;30(11):2472-7; discussion 2477-8
10548686
Curr Neurovasc Res. 2016;13(2):121-6
26972078
Acta Neurochir Suppl. 2008;105:59-65
19066084
Neurosci Lett. 1992 Dec 14;148(1-2):137-40
1300486
Stroke. 2015 Nov;46(11):3088-92
26396030
J Neuroimmunol. 2009 Jan 3;206(1-2):112-7
19058859
J Neurosci Methods. 2002 Jun 30;117(2):207-14
12100987
J Cereb Blood Flow Metab. 2006 May;26(5):654-65
16121126
Oxid Med Cell Longev. 2016;2016:3215391
26843907
J Neurochem. 2007 Aug;102(3):900-12
17561941
Neurol Res. 2005 Apr;27(3):268-79
15845210
J Cereb Blood Flow Metab. 2016 Dec;36(12):2134-2145
26661220
Nat Protoc. 2008;3(1):122-8
18193028
J Cereb Blood Flow Metab. 2017 Mar;37(3):967-979
27174997
Cell Mol Neurobiol. 2015 Mar;35(2):147-57
25179154
J Cereb Blood Flow Metab. 2013 Jan;33(1):37-47
22968321
Neurology. 2002 Feb 26;58(4):624-9
11865143