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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation

Authors: Hiramani Dhungana, Mikko T. Huuskonen, Merja Jaronen, Sighild Lemarchant, Humair Ali, Velta Keksa-Goldsteine, Gundars Goldsteins, Katja M. Kanninen, Jari Koistinaho, Tarja Malm

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Ischemic stroke is one of the main causes of death and disability worldwide. It is caused by the cessation of cerebral blood flow resulting in the insufficient delivery of glucose and oxygen to the neural tissue. The inflammatory response initiated by ischemic stroke in order to restore tissue homeostasis in the acute phase of stroke contributes to delayed brain damage.

Methods

By using in vitro models of neuroinflammation and in vivo model of permanent middle cerebral artery occlusion, we demonstrate the neuroprotective and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO).

Results

SSO significantly reduced the lipopolysaccharide/interferon-γ-induced production of nitric oxide, interleukin-6 and tumor necrosis factor-α, and the protein levels of inflammatory enzymes including nitric oxide synthase 2, cyclooxygenase-2 (COX-2), and p38 mitogen-activated protein kinase (MAPK) in microglia, without causing cell toxicity. Although SSO failed to directly alleviate glutamate-induced excitotoxicity in murine cortical neurons, it prevented inflammation-induced neuronal death in microglia-neuron co-cultures. Importantly, oral administration of SSO in Balb/c mice subjected to permanent occlusion of the middle cerebral artery reduced microglial activation in the peri-ischemic area and attenuated brain damage. This in vivo neuroprotective effect of SSO was associated with a reduction in the COX-2 and heme oxygenase-1 immunoreactivities.

Conclusions

Our results suggest that SSO is an anti-inflammatory and a possible therapeutic candidate in diseases such as stroke where inflammation is a central hallmark.
Literature
1.
Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22:391–7.CrossRefPubMed
2.
Vidale S, Consoli A, Arnaboldi M, Consoli D. Postischemic inflammation in acute stroke. J Clin Neurol (Seoul, Korea), 13. 2017:1–9.
3.
4.
5.
6.
Dong HJ, Shang CZ, Peng DW, Xu J, PX X, Zhan L, Wang P. Curcumin attenuates ischemia-like injury induced IL-1beta elevation in brain microvascular endothelial cells via inhibiting MAPK pathways and nuclear factor-kappaB activation. Neurol Sci. 2014;35:1387–92.CrossRefPubMed
7.
Tikka TM, Koistinaho JE. Minocycline provides neuroprotection against N-methyl-d-aspartate neurotoxicity by inhibiting microglia. J Immunol. 2001;166:7527–33.CrossRefPubMed
8.
Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A. 1998;95:15769–74.CrossRefPubMedPubMedCentral
9.
Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA, Lizasoain I. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation. 2007;115:1599–608.CrossRefPubMed
10.
Minnerup J, Sutherland BA, Buchan AM, Kleinschnitz C. Neuroprotection for stroke: current status and future perspectives. Int J Mol Sci. 2012;13:11753–72.CrossRefPubMedPubMedCentral
11.
Abe T, Shimamura M, Jackman K, Kurinami H, Anrather J, Zhou P, Iadecola C. Key role of CD36 in Toll-like receptor 2 signaling in cerebral ischemia. Stroke. 2010;41:898–904.CrossRefPubMedPubMedCentral
12.
13.
Cho S, Park EM, Febbraio M, Anrather J, Park L, Racchumi G, Silverstein RL, Iadecola C. The class B scavenger receptor CD36 mediates free radical production and tissue injury in cerebral ischemia. J Neurosci. 2005;25:2504–12.CrossRefPubMed
14.
Simantov R, Silverstein RL. CD36: a critical anti-angiogenic receptor. Front Biosci. 2003;8:s874–82.CrossRefPubMed
15.
Malm T, Mariani M, Donovan LJ, Neilson L, Landreth GE. Activation of the nuclear receptor PPARδ is neuroprotective in a transgenic mouse model of Alzheimer’s disease through inhibition of inflammation. J Neuroinflammation. 2015;12:7.CrossRefPubMedPubMedCentral
16.
Gresa-Arribas N, Viéitez C, Dentesano G, Serratosa J, Saura J, Solà C. Modelling neuroinflammation in vitro: a tool to test the potential neuroprotective effect of anti-inflammatory agents. Plos One. 2012;7:e45227.
17.
Dhungana H, Rolova T, Savchenko E, Wojciechowski S, Savolainen K, Ruotsalainen A-K, Sullivan P, Koistinaho J, Malm T. Western-type diet modulates inflammatory responses and impairs functional outcome following permanent middle cerebral artery occlusion in aged mice expressing the human apolipoprotein E4 allele. J Neuroinflammation. 2013;10:102.CrossRefPubMedPubMedCentral
18.
Hrometz SL, Ebert JA, Grice KE, Nowinski SM, Mills EM, Myers BJ, Sprague JE. Potentiation of Ecstasy-induced hyperthermia and FAT/CD36 expression in chronically exercised animals. Temperature. 2016;3:557–66.CrossRef
19.
Liu H, Xu W, Yu Q, Yang Q. 4,4′-diaponeurosporene-producing Bacillus subtilis increased mouse resistance against S. Typhimurium infection in a CD36 dependent manner. Front Immunol. 2017;8
20.
Shuaib A, Xu Wang C, Yang T, Noor R. Effects of nonpeptide V(1) vasopressin receptor antagonist SR-49059 on infarction volume and recovery of function in a focal embolic stroke model. Stroke. 2002;33:3033–7.CrossRefPubMed
21.
Karunakaran U, Moon JS, Lee HW, Won KC. CD36 initiated signaling mediates ceramide-induced TXNIP expression in pancreatic beta-cells. Biochim Biophys Acta (BBA) - Mol Basis Dis. 2015;1852:2414–22.CrossRef
22.
Kim JY, Kawabori M, Yenari MA. Innate inflammatory responses in stroke: mechanisms and potential therapeutic targets. Curr Med Chem. 2014;21:2076–97.CrossRefPubMedPubMedCentral
23.
Chan ED, Riches DWH. IFN-γ + LPS induction of iNOS is modulated by ERK, JNK/SAPK, and p38<sup> <em>mapk</em> </sup> in a mouse macrophage cell line. Am J Physiol Cell Physiol. 2001;280:C441–50.PubMed
24.
Jung YS, Park JH, Kim H, Kim SY, Hwang JY, Hong KW, Bae SS, Choi BT, Lee S-W, Shin HK. Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice. Acta Pharmacol Sin. 2016;37:1031–44.CrossRefPubMedPubMedCentral
25.
W-J O, Jung U, Eom H-S, Shin H-J, Park H-R. Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling. Molecules. 2013;18:9195.CrossRef
26.
Kilic U, Kilic E, Matter CM, Bassetti CL, Hermann DM. TLR-4 deficiency protects against focal cerebral ischemia and axotomy-induced neurodegeneration. Neurobiol Dis. 2008;31:33–40.CrossRefPubMed
27.
Zhao S-C, Ma L-S, Chu Z-H, Xu H, Wu W-Q, Liu F. Regulation of microglial activation in stroke. Acta Pharmacol Sin. 2017;38:445–58.CrossRefPubMed
28.
Cao CX, Yang QW, Lv FL, Cui J, Fu HB, Wang JZ. Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice. Biochem Biophys Res Commun. 2007;353:509–14.CrossRefPubMed
29.
Barone FC, Irving EA, Ray AM, Lee JC, Kassis S, Kumar S, Badger AM, White RF, McVey MJ, Legos JJ, et al. SB 239063, a second-generation p38 mitogen-activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia. J Pharmacol Exp Ther. 2001;296:312–21.PubMed
30.
Legos JJ, Erhardt JA, White RF, Lenhard SC, Chandra S, Parsons AA, Tuma RF, Barone FC. SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia. Brain Res. 2001;892:70–7.CrossRefPubMed
31.
Piao CS, Kim JB, Han PL, Lee JK. Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult. J Neurosci Res. 2003;73:537–44.CrossRefPubMed
32.
Nurmi A, Lindsberg PJ, Koistinaho M, Zhang W, Juettler E, Karjalainen-Lindsberg ML, Weih F, Frank N, Schwaninger M, Koistinaho J. Nuclear factor-kappaB contributes to infarction after permanent focal ischemia. Stroke. 2004;35:987–91.CrossRefPubMed
33.
Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M. NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat Med. 1999;5:554–9.CrossRefPubMed
34.
Lv Y, Qian Y, Ou-Yang A, Fu L. Hydroxysafflor yellow A attenuates neuron damage by suppressing the lipopolysaccharide-induced TLR4 pathway in activated microglial cells. Cell Mol Neurobiol. 2016;36:1241–56.CrossRefPubMed
35.
Coort SLM, Willems J, Coumans WA, van der Vusse GJ, Bonen A, Glatz JFC, Luiken JJFP. Sulfo-N-succinimidyl esters of long chain fatty acids specifically inhibit fatty acid translocase (FAT/CD36)-mediated cellular fatty acid uptake. Mol Cell Biochem. 2002;239:213–9.CrossRefPubMed
36.
Kuda O, Pietka TA, Demianova Z, Kudova E, Cvacka J, Kopecky J, Abumrad NA. Sulfo-N-succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164: SSO also inhibits oxidized low density lipoprotein uptake by macrophages. J Biol Chem. 2013;288:15547–55.CrossRefPubMedPubMedCentral
37.
Pohl J, Ring A, Korkmaz U, Ehehalt R, Stremmel W. FAT/CD36-mediated long-chain fatty acid uptake in adipocytes requires plasma membrane rafts. Mol Biol Cell. 2005;16:24–31.CrossRefPubMedPubMedCentral
38.
39.
Kunz A, Abe T, Hochrainer K, Shimamura M, Anrather J, Racchumi G, Zhou P, Iadecola C. Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion. J Neurosci. 2008;28:1649–58.CrossRefPubMedPubMedCentral
40.
Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K. Membrane sorting of Toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem. 2006;281:31002–11.CrossRefPubMed
41.
Cho S, Febbraio M. CD36: an inflammatory mediator in acute brain injury. In: Chen J, Hu X, Stenzel-Poore M, Zhang JH, editors. Immunological mechanisms and therapies in brain injuries and stroke. New York, NY: Springer New York; 2014. p. 321–47.CrossRef
42.
Woo MS, Wang X, Faustino JV, Derugin N, Wendland MF, Zhou P, Iadecola C, Vexler ZS. Genetic deletion of CD36 enhances injury after acute neonatal stroke. Ann Neurol. 2012;72:961–70.CrossRefPubMedPubMedCentral
43.
Cao D, Luo J, Chen D, Xu H, Shi H, Jing X, Zang W. CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells. Sci Rep. 2016;6:23132.
44.
Kim E, Tolhurst AT, Szeto HH, Cho S. Targeting CD36-mediated inflammation reduces acute brain injury in transient, but not permanent, ischemic stroke. CNS Neurosci Therapeut. 2015;21:385–91.CrossRef
45.
Iadecola C, Gorelick PB. The janus face of cyclooxygenase-2 in ischemic stroke: shifting toward downstream targets. Stroke. 2005;36:182–5.CrossRefPubMed
46.
Houssier M, Raoul W, Lavalette S, Keller N, Guillonneau X, Baragatti B, Jonet L, Jeanny JC, Behar-Cohen F, Coceani F, et al. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents. PLoS Med. 2008;5:e39.CrossRefPubMedPubMedCentral
47.
Bujold K, Rhainds D, Jossart C, Febbraio M, Marleau S, Ong H. CD36-mediated cholesterol efflux is associated with PPARγ activation via a MAPK-dependent COX-2 pathway in macrophages. Cardiovasc Res. 2009;83:457–64.CrossRefPubMed
48.
Kuda O, Jenkins CM, Skinner JR, Moon SH, Su X, Gross RW, Abumrad NA. CD36 protein is involved in store-operated calcium flux, phospholipase A2 activation, and production of prostaglandin E2. J Biol Chem. 2011;286:17785–95.CrossRefPubMedPubMedCentral
49.
Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci. 2016;73:3221–47.CrossRefPubMedPubMedCentral
50.
Yao Y, Miao W, Liu Z, Han W, Shi K, Shen Y, Li H, Liu Q, Fu Y, Huang D, Shi F-D. Dimethyl fumarate and monomethyl fumarate promote post-ischemic recovery in mice. Transl Stroke Res. 2016;7:535–47.CrossRefPubMedPubMedCentral
51.
Peng Z, Wang S, Chen G, Cai M, Liu R, Deng J, Liu J, Zhang T, Tan Q, Hai C. Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway. Neurochem Res. 2015;40:661–73.CrossRefPubMed
52.
Wang B, Tian S, Wang J, Han F, Zhao L, Wang R, Ning W, Chen W, Qu Y. Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke. Brain Res. 2015;30:89–97.CrossRef
53.
Suh SJ, Chung TW, Son MJ, Kim SH, Moon TC, Son KH, Kim HP, Chang HW, Kim CH. The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. Arch Biochem Biophys. 2006;447:136–46.CrossRefPubMed
54.
Rushworth SA, MacEwan DJ, O’Connell MA. Lipopolysaccharide-induced expression of NAD(P)H:quinone oxidoreductase 1 and heme oxygenase-1 protects against excessive inflammatory responses in human monocytes. J Immunol (Baltimore, Md : 1950). 2008;181:6730–7.CrossRef
55.
Kwon Y-W, Cheon SY, Park SY, Song J, Lee J-H. Tryptanthrin suppresses the activation of the LPS-treated BV2 microglial cell line via Nrf2/HO-1 antioxidant signaling. Front Cell Neurosci. 2017;11:18.CrossRefPubMedPubMedCentral
56.
Min KJ, Kim JH, Jou I, Joe EH. Adenosine induces hemeoxygenase-1 expression in microglia through the activation of phosphatidylinositol 3-kinase and nuclear factor E2-related factor 2. Glia. 2008;56:1028–37.CrossRefPubMed
57.
del Zoppo GJ, Milner R, Mabuchi T, Hung S, Wang X, Berg GI, Koziol JA. Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke. 2007;38:646–51.CrossRefPubMed
58.
Pun PBL, Lu J, Moochhala S. Involvement of ROS in BBB dysfunction. Free Radic Res. 2009;43:348–64.CrossRefPubMed
Metadata
Title
Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced neuroinflammation
Authors
Hiramani Dhungana
Mikko T. Huuskonen
Merja Jaronen
Sighild Lemarchant
Humair Ali
Velta Keksa-Goldsteine
Gundars Goldsteins
Katja M. Kanninen
Jari Koistinaho
Tarja Malm
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-1010-7

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