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1 Supplemental Table 1: Impact of selected molecules involved in post-ischemic inflammation on stroke outcome Pathway Protein Species/strain Manipulation Model Days after I or I/R % Change a REF Interleukins IL-1α/β C57 double KO tMCAO 1 -60 1 ICE/Caspase 1 C57 KO pMCAO 1 -52 2 IL-1RA C57 KO tMCAO 1 +300 3 IL-1R1 C57 KO HI 1 -67 4 IL-6 C57 KO tMCAO 1 +65 5 C57 neutr Ab ip tMCAO 1 +32 6 rat rec protein icv pMCAO 1 +75 7 IL-10 SHR viral delivery icv pMCAO 5 -53 8 SHR viral delivery icv BCCAO 5 -45 8 C57 transgenic pMCAO 4 -40 9 SHR rec protein icv pMCAO 1 -20 10 SHR rec protein iv pMCAO 1 -40 10 C57 KO pMCAO 1 +29 11 IL-12 C57 neutr Ab ip tMCAO 7 -63 12 IL-17 C57 KO tMCAO 1, 4 -33 13 IL-18 C57 KO tMCAO 1 ne 14 C57 KO HI 3 -21 15 IL-20 rat neutr Ab iv tMCAO 3 -24 16 IL-23 C57 KO tMCAO 1, 4 -50 13 C57 neutr Ab ip tMCAO 7 -63 12 Interferons IFNγ C57 KO tMCAO 1, 4 ne 13 C57 KO tMCAO 1 -60 17 IFNβ rat rec protein sc tMCAO 1 -67 18 rat rec protein iv tMCAO 8 ne 19 C57 KO tMCAO 3 ne 20 TNF family TNF C57x129S6 KO pMCAO 1, 5 +59 21 SHR rec protein icv tMCAO 1 +21 22 SHR neutr Ab icv pMCAO 1 -20 22 SHR decoy receptor icv pMCAO 1 -26 22 rat TACE enzyme inhibitor ip pMCAO 1 -58 23 TNFR C57 double KO tMCAO 1 +36 24 TNFR1 C57 KO tMCAO 1 +21 25 TNFR2 C57 KO tMCAO 1 +3 25 CD95/Fas lpr loss of function mutant tMCAO 1 -64 26 TRAIL C57 decoy receptor icv BCCAO 3 -30 27 CD40/CD40L C57 KO tMCAO 1 -35 28 Nature Medicine doi:10.1038/nm.2399

Transcript of 1 Supplemental Table 1: Impact of selected molecules ... · 1 Supplemental Table 1: Impact of...

Page 1: 1 Supplemental Table 1: Impact of selected molecules ... · 1 Supplemental Table 1: Impact of selected molecules involved in post-ischemic inflammation on stroke outcome Pathway Protein

1 Supplemental Table 1: Impact of selected molecules involved in post-ischemic inflammation on stroke outcome

Pathway Protein Species/strain Manipulation Model Days after I or I/R % Changea REF Interleukins IL-1α/β C57 double KO tMCAO 1 -60 1 ICE/Caspase 1 C57 KO pMCAO 1 -52 2 IL-1RA C57 KO tMCAO 1 +300 3 IL-1R1 C57 KO HI 1 -67 4 IL-6 C57 KO tMCAO 1 +65 5 C57 neutr Ab ip tMCAO 1 +32 6 rat rec protein icv pMCAO 1 +75 7 IL-10 SHR viral delivery icv pMCAO 5 -53 8 SHR viral delivery icv BCCAO 5 -45 8 C57 transgenic pMCAO 4 -40 9 SHR rec protein icv pMCAO 1 -20 10 SHR rec protein iv pMCAO 1 -40 10 C57 KO pMCAO 1 +29 11 IL-12 C57 neutr Ab ip tMCAO 7 -63 12 IL-17 C57 KO tMCAO 1, 4 -33 13 IL-18 C57 KO tMCAO 1 ne 14 C57 KO HI 3 -21 15 IL-20 rat neutr Ab iv tMCAO 3 -24 16 IL-23 C57 KO tMCAO 1, 4 -50 13 C57 neutr Ab ip tMCAO 7 -63 12 Interferons IFNγ C57 KO tMCAO 1, 4 ne 13 C57 KO tMCAO 1 -60 17 IFNβ rat rec protein sc tMCAO 1 -67 18 rat rec protein iv tMCAO 8 ne 19 C57 KO tMCAO 3 ne 20 TNF family TNF C57x129S6 KO pMCAO 1, 5 +59 21 SHR rec protein icv tMCAO 1 +21 22 SHR neutr Ab icv pMCAO 1 -20 22 SHR decoy receptor icv pMCAO 1 -26 22 rat TACE enzyme inhibitor ip pMCAO 1 -58 23 TNFR C57 double KO tMCAO 1 +36 24 TNFR1 C57 KO tMCAO 1 +21 25 TNFR2 C57 KO tMCAO 1 +3 25 CD95/Fas lpr loss of function mutant tMCAO 1 -64 26 TRAIL C57 decoy receptor icv BCCAO 3 -30 27 CD40/CD40L C57 KO tMCAO 1 -35 28

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2 Pathway Protein Species/strain Manipulation Model Days after I or I/R % Changea REF TGF family TGFβ rat decoy receptor cerebr tMCAO 1 +253 29 rat rec protein icv BCCAO 7 -27 30 CD1 viral delivery icv tMCAO 1 -41 31 Chemokines CCL2/MCP-1 C57 KO pMCAO 1 -29 32 C57 KO tMCAO 2 -31 33 SHR viral delivery of DN mutant icv pMCAO 5 -28 34 C57xDBA/2 transgenic pMCAO 1, 2 +70 35 CCL5/RANTES C57 KO tMCAO 1 -43 36 C57 CCL5 KO BM tMCAO 1 -40 36 CCL20/MIP-3α rat neutr Ab icv tMCAO 2 -38 37 CX3CL1/Fractalkine 129Sv/J KO tMCAO 1 -29 38 CXCL1 rat neutr Ab ip tMCAO 7 -28 39 CXCL8/IL-8 rat pharm antagonist iv/sc tMCAO 1 -44 40 rat pharm antagonist iv/sc pMCAO 1 ne 40 MIF C57 KO tMCAO 7 -23 41 CCR5 C57 KO pMCAO 2, 7 +36 42 CCR2 C57 KO tMCAO 1, 5 -58 43 C57 KO tMCAO 1, 2, 4, 7 ne 44 CCR5/2 ddY small-molecule inhbitor icv, iv tMCAO 2 -30 45 CXCR1/2/IL-8 receptor rat pharm antagonist iv/sc tMCAO 1 -44 40 rat pharm antagonist iv/sc pMCAO 1 ne 40 CX3CR1 C57 KO tMCAO 1 -32 46 TLR, DAMPR TLR2 C57 KO tMCAO 3 -58 47 C57 KO tMCAO 3 -30 48 C57 KO tMCAO 2 -27 49 C57 KO tMCAO 2 -44 50 C57 KO tMCAO 3 -83 51 TLR3 Balbc KO tMCAO 1 ne 52 TLR4 C57 KO tMCAO 1 -58 52 C57 KO tMCAO 1 -33 53 C3H/HeJ loss of function mutant tMCAO 1 -33 54

C3H/HeJ, C57BL/10ScNJ loss of function mutant pMCAO 1, 7 -24 55

C3H/HeJ loss of function mutant tMCAO 1 -33 56 C3H/HeJ loss of function mutant tMCAO 3 -50 51 C57BL/10ScNJ loss of function mutant BCCAO 3 -54 57 TLR9 Balb/c KO tMCAO 1 ne 52

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3 Pathway Protein Species/strain Manipulation Model Days after I or I/R % Changea REF HMGB1 C57 neutr Ab ip pMCAO 2 -28 58 rat neutr Ab iv tMCAO 1, 2 -76 59 C57 rec protein icv pMCAO 1 +47 60 C57 rec protein icv tMCAO 1 +36 53 rat rec protein icv tMCAO 1, 2 +175 59 Amyloidβ APP695.SWE tg transgenic pMCAO 1 +27 61 RAGE C57 KO pMCAO 2 -50 58 SR-A C57 KO tMCAO 1 -64 62 CD36 C57 KO tMCAO 3 -48 63,64 CD47 C57 KO tMCAO 1, 3 -29 65 CD39 C57BL/6 × 129/J KO tMCAO 1 +250 66 P2X7 rat pharm inhibitor ip pMCAO 1 -45 67 rat pharm inhibitor icv tMCAO 3 +50 68 P2 receptors rat pharm inhibitor icv pMCAO 1, 7 -36 69 A2AR C57 KO tMCAO 1 -63 70 Adhesion molec. P-selectin C57 KO tMCAO 1 -77 71 rat block Ab iv tMCAO 2 -42 72 rat block Ab iv pMCAO 1 -50 73 C57 E-/P-Selectin double KO tMCAO 1 ne 74 E-selectin C57 block Ab iv tMCAO 1 -63 75 C57 E-/P-Selectin double KO tMCAO 1 ne 74 L-selectin rabbit block Ab iv tICA 8 ne 76 Vcam-1 rat block Ab iv tMCAO 2 ne 77 CD1 block Ab iv tMCAO 4 ne 77 Icam-1 C57 block Ab iv tMCAO 1 -44 78 C57 KO pMCAO 2 -40 79 C57 KO tMCAO 2 -47 80 α4 integrin rat block Ab iv tMCAO 1 -57 81 rat block Ab ip tMCAO 2 -31 82 β2 integrin rat rec inhibitor pMCAO 7 ne 83 Enzymes iNOS C57xSV129 KO pMCAO 4 -28 84 COX-2 C57 KO pMCAO 4 -38 85 PTGES C57 KO tMCAO 1 -60 86

5-lipoxigenase C57 KO pMCAO, tMCAO 7 ne 87

Nox2/gp91phox C57xE129 KO tMCAO 1 -50 88 myeloperoxidase C57 KO tMCAO 1 +56 89 elastase rat pharm inhibitor pMCAO 1 -30 90

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4 Pathway Protein Species/strain Manipulation Model Days after I or I/R % Changea REF MMP9 C57 KO pMCAO 1 ne 91 C57 KO tMCAO 1 -37 91 C57 KO tMCAO 1 -37 92 Complement C1q C57 KO tMCAO 1 ne 93 C3a C57 receptor antagonist ip tMCAO 1 -42 94 C57 receptor antagonist ip pMCAO 1 ne 94 C57 KO tMCAO 1 -34 93 C57 KO tMCAO 7 +24 95 C5a C57 receptor antagonist ip tMCAO 1 -21 96 C57 KO tMCAO 1 ne 93 CD59a C57 KO tMCAO 3 +67 97 C57 KO tMCAO 2 ne 97 CD93/C1q receptor 1 C57 KO tMCAO 2, 3 +154 98 CD64/FcγRI C57 KO tMCAO 1, 3, 14 -39 99 Growth factors CSF1/M-CSF C3H/HeJ rec protein cereb, ip fCTX les. 6 -50 100 op/op loss of function mutant fCTX les. 6 +121 101 op/op rec protein cereb, ip fCTX les. 6 -50 102 CSF2/GM-CSF rat rec protein iv tMCAO 3 -35 103 rat rec protein iv BCCAO 3 -27 103 rat rec protein ia tMCAO 2 -48 104 CSF3/G-CSF rat rec protein ip tMCAO 1 -52 105 C57/129 KO tMCAO 2 +41 106 C57 rec protein iv tMCAO 1, 3 -34 107 rat rec protein iv tMCAO 1 -53 108 rat rec protein iv tMCAO 1 -37 109 BDNF rat rec protein icv pMCAO 1 -33 110 rat viral delivery cereb tMCAO 42-49 -21 111 NGF rat rec protein icv pMCAO 1 ne 112 C57 transgenic pMCAO 1 -40 113 rat viral delivery cereb tMCAO 42-49 ne 111 GDNF rat rec protein cereb, icv tMCAO 1 -75 114 rat rec protein cereb pMCAO 1 -49 115 rat viral delivery cereb tMCAO 3 -42 116 C57 viral delivery cereb tMCAO 3 -50 117 C57 rec TAT-fusion protein iv tMCAO 3 -90 118 FGF-2 rat rec protein iv pMCAO 1 -52 119 rat rec protein iv tMCAO 7 -40 120

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5 Pathway Protein/metabolite Species/strain Manipulation Model Days after I or I/R % Changea REF rat viral delivery icv pMCAO 2 -44 121 HB-EGF rat rec protein iv tMCAO 7 -45 122 rat viral delivery icv tMCAO 8, 28 ne 123 IGF-1 rat rec protein icv sc tMCAO 3 -64 124 EPO rat rec protein ip tMCAO 1 -60 125 rat rec protein iv tMCAO 1 -50 126 rat rec protein iv tMCAO 1 -50 127 VEGF C57 decoy receptor ip tMCAO 84 -30 128 rat viral delivery icv tMCAO 2 +30 129 rat rec protein icv tMCAO 3, 7, 14, 28 -35 130 C57 transgenic tMCAO 1 -45 131 C57 rec protein icv tMCAO 1 -35 132 Lipid mediators Lipoxin A4 rat LipoxinA4-methylester icv tMCAO 1 -50 133 Docosanoids C57 10,17S-docosatriene icv tMCAO 2 -50 134 Unclassified fetuin-A C57 KO pMCAO 1 ne 135 rat rec protein iv pMCAO 1 -90 135

Abbreviations: Ab, antibodies; block, blocking; C57, C57Bl6; cerebr, cerebral; DN, dominant negative; fCTX les., focal cortical lesions; HI, hypoxia-ischemia; I, ischemia; I/R, ischemia/reperfusion; ia, intra-arterial; icv, intracerebroventricular; ip, intraperitoneal; iv, intravenous; KO, knock-out; ne, no effect; neutr, neutralizing; rec, recombinant; pMCAO, permanent middle cerebral artery occlusion; sc, subcutaneous; SHR, spontaneous hypertensive rats; tICA, transient internal carotid artery occlusion; tMCAO, transient middle cerebral artery occlusion; Notes: a, % increase (+) or decrease (-) of infarct volumes or neuronal cell loss when compared to control animals undergoing the same ischemic treatment.

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