Propofol Inhibits NLRP3 Inflammasome and Attenuates Blast-Induced Traumatic Brain Injury in Rats.
Increasing evidence has demonstrated that inflammatory response plays a crucial role in the pathogenesis of secondary injury following blast-induced traumatic brain injury (bTBI). Propofol, a lipid-soluble intravenous anesthetic, has been shown to possess therapeutic benefit during neuroinflammation on various brain injury models. Recent findings have proved that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome involved in the process of the inflammatory response following brain trauma, may probably be a promising target in the treatment of bTBI. Rats were randomly divided into six groups (n = 8): normal group; bTBI-12 and 24 h group; bTBI-12 h and bTBI-24 h group treated with propofol; and bTBI treated with control dimethyl sulfoxide (DMSO) group. The effect of propofol on the expression and activation of NLRP3 inflammasome and the degree of oxidative stress and inflammatory cascades, as well as the brain trauma biomarkers were evaluated in rats suffering from bTBI. The enhanced expressions and activation of NLRP3 inflammasome in the cerebral cortex of bTBI rats were substantially suppressed by the administration of propofol, which was paralleled with the decreased oxidative stress, cytokines production, and the amelioration of cerebral cortex damage. Our results have, for the first time, revealed that over-activation of NLRP3 inflammasome in the cerebral cortex may be involved in the process of neuroinflammation during the secondary injury of bTBI in rats. Propofol might relieve the inflammatory response and attenuate brain injury by inhibiting ROS and reluctant depressing NLRP3 inflammasome activation and pro-inflammatory cytokines maturation.
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China.
Jie
J
Ma
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China.
Wenjing
W
Xiao
Department of Orthopaedics, Chengdu Second People's Hospital, Chengdu, Sichuan, 610017, People's Republic of China.
Junrui
J
Wang
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China.
Juan
J
Wu
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China.
Jiandong
J
Ren
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China.
Jun
J
Hou
Department of Neurosurgery, The 306th Hospital of PLA, NO.9, Anxiang Beili, Deshengmen, Chaoyang District, Beijing, 100101, China. gujianwen5000@sina.com.|Department of Neurosurgery, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China. gujianwen5000@sina.com.
Jianwen
J
Gu
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China. fankh2012@sina.com.
Kaihua
K
Fan
Department of Pharmacy, Chengdu Military General Hospital, No.270, Rongdu Aveneue, Jinniu District, Chengdu, Sichuan, 610083, China. botao_yu@sina.com.
Botao
B
Yu
D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D058847:Inflammasomes / Q000037:antagonists & inhibitors*; D007249:Inflammation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D017382:Reactive Oxygen Species; D015742:Propofol
NLRP3 inflammasome; blast-induced traumatic brain injury; inflammation; oxidative stress; propofol
Brain Inj. 2014;28(7):879-95
24766453
Eur J Anaesthesiol. 2005 Jun;22(6):467-70
15991512
J Int Neuropsychol Soc. 2009 Jan;15(1):1-8
19128523
Prog Neurobiol. 2000 Dec;62(6):649-71
10880854
Cell Biochem Biophys. 2013 Nov;67(2):615-22
23494261
J Neurotrauma. 2000 Oct;17(10):871-90
11063054
J Immunol. 2011 Nov 15;187(10 ):5440-51
22003197
PLoS One. 2014 Sep 04;9(9):e106680
25188406
J Neurotrauma. 2007;24 Suppl 1:S1-106
17511534
Curr Opin Immunol. 2009 Feb;21(1):10-6
19223160
JAMA. 2011 Aug 3;306(5):477-9
21813422
Yao Xue Xue Bao. 2009 Apr;44(4):344-9
19545049
Br J Pharmacol. 2006 Jan;147 Suppl 1:S232-40
16402109
Curr Pharm Des. 2004;10(29):3639-49
15579060
Am J Respir Crit Care Med. 2002 Jan 1;165(1):54-60
11779730
Lancet Neurol. 2013 Sep;12 (9):882-893
23884075
Nat Immunol. 2010 Feb;11(2):136-40
20023662
Brain Res. 2011 Sep 2;1410:24-32
21783180
Science. 2008 May 2;320(5876):674-7
18403674
Neurosci Lett. 2005 Sep 23;386(1):40-5
16024175
Brain Behav Immun. 2012 Nov;26(8):1191-201
22728326
Cell. 2010 Mar 19;140(6):821-32
20303873
J Cereb Blood Flow Metab. 2010 Feb;30(2):255-66
19809467
J Neurotrauma. 2004 Feb;21(2):149-61
15000756
Inflammopharmacology. 2013 Aug;21(4):309-20
23296919
Ann Biomed Eng. 2012 Jan;40(1):185-202
22012085
Mediators Inflamm. 2014;2014:930894
25214720
Acta Neurochir Suppl. 2000;76:397-9
11450053
Science. 2010 Jan 15;327(5963):296-300
20075245
Philos Trans R Soc Lond B Biol Sci. 2011 Jan 27;366(1562):241-50
21149359
Front Immunol. 2012 Sep 18;3:288
23024646
J Clin Neurosci. 2009 May;16(5):614-9
19285410
Nat Immunol. 2008 Aug;9(8):857-65
18604209
Neurochem Res. 2011 Oct;36(10):1724-31
21556843
Childs Nerv Syst. 2010 Feb;26(2):221-6
19940996
Neurochem Res. 2013 Oct;38(10 ):2072-83
23892989
J Cereb Blood Flow Metab. 2014 Apr;34(4):660-7
24424382
J Neurol Sci. 2010 Jul 15;294(1-2):23-8
20478573