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Table 1 TLRs preconditionings and effects

From: Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment

Animal Model Preconditioning time/approach TLR/ischemia Result and mechanism Author Reference
Mice MCAO, 60-min ischemia, 24-h reperfusion 72 h/12-min ischemia Ischemic preconditioning Decrease brain infarction volume, and IRF gene participate in brain protection Stevens SL [79]
Mice MCAO, 60-min ischemia, 6-h reperfusion 24 h/IP TLR2, Pam3CSK4 Decrease brain infarction and edema, improve neurological function, and maintain BBB function Hua F [60]
Mice MCAO, 45-min ischemia, 24-h reperfusion 72 h/subcutaneous injection TLR3, poly-ICLC Decrease brain infarction volume and improve neurological function Packard AEB [63]
Mice MCAO, 120-min ischemia, 22-h reperfusion 24 h/systemic injection TLR3 poly-IC Decrease brain infarction volume and neurological defect and lower the levels of TNF-α and IL-6 in cortex and striatum Pan LN [66]
Mice MCAO, 60-min ischemia, 24-h reperfusion 1 h/IP TLR3 poly-IC Decrease brain infarction and prevention of Fas/FADD interaction Zhang X [67]
Spontaneously hypertension rats MCAO, 120-min ischemia, 22-h reperfusion 2, 3, 4 days/IV TLR4 LPS Decrease brain infarction volume, mediated by TNF-α Tasaki K [72]
Mice MCAO, 120-min ischemia, 47-h reperfusion 48 h/IP TLR4 LPS Decrease brain infarction volume, inhibit the infiltration of neutrophil and activation of the microglia Rosenzweig HL [73]
Mice MCAO, 40-, 45-, 60-min ischemia, 24-h reperfusion 72 h/IP TLR4 LPS Decrease brain infarction volume that was mediated by IRF3 Marsh B [61]
Mice MCAO, 40-to 60-min ischemia, 24-h reperfusion 72 h/subcutaneous injection TLR4 LPS Decrease brain infarction volume, and TRIF-IRF3 play vital role Vartanian KB [58]
Mice MCAO, 60-min ischemia, 24-h reperfusion 72 h/IP TLR4 Decrease brain infarction volume, and inhibit TNF-α signaling pathway after cerebral ischemia Rosenzweig HL [76]
Mice MCAO, 45-to 60-min ischemia, 23-h reperfusion 72 h/subcutaneous injection TLR7 GDQ Decrease brain infarction volume and neurological functional score that was protected through I type interferon Leung PY [62]
Mice MCAO, 60-min ischemia, 72-h reperfusion 30 min/IV TLR8 R848 Increase neurological function defect and mortality, activate pro-apoptotic JNK pathway and inflammation Tang SC [56]
Mice MCAO, 60-min ischemia, 24-h reperfusion 72 h/IP TLR9 CpG-ODN Decrease brain infarction volume and TNF-α play a vital role Stevens SL [64]
Mice MCAO, 60-min ischemia, 24-h reperfusion 72 h/IP or subcutaneous injection TLR9 CpG-ODN Decrease brain infarction volume and IRF gene participate in cerebral protection after ischemia Stevens SL [79]
Mice MCAO, 60-min ischemia, 24-h reperfusion 1 h/IP TLR9 CpG-ODN Decrease brain infarction and activation of PI3K/Akt signaling Lu C [78]
  1. MCAO: middle cerebral artery occlusion; IP: intraperitoneal injection; IV: intravenous injection; HI: hypoxic-ischemic; ICA: internal carotid artery; IRF: interferon regulatory factor; TLR: toll-like receptor; BBB: blood-brain barrier; Poly-IC: polycytidylic acid; Poly-ICLC: polyinosinic-polycytidylic acid; FADD: Fas-Associated protein with Death Domain; LPS: lipopolysaccharide; IRF: interferon regulatory factor; TRIF: TIR-domain-containing adapter-inducing interferon-β; GDQ: gardiquimod; JNK: c-Jun N-terminal kinase; CpG-ODN: CpG-motif oligodeoxynucleotide. MCAO, 60-min ischemia, 24-h reperfusion: the mice was employed MCAO (cerebral ischemia) 60 min followed by reperfusion 24 h. 1 h/IP: mice were injected intraperitoneally with TLRs ligand 1 h prior to cerebral ischemia.
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