Introduction
Introduction of TLRs and their signaling pathways
Toll-like receptors and cerebral ischemic injury
TLR2 and cerebral ischemic injury
TLR3, TLR9, and cerebral ischemic injury
TLR4 and cerebral ischemic injury
TLR8 and cerebral ischemic injury
Preconditioning with TLR ligands and cerebral ischemic injury
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] |
TLR2 ligand preconditioning and ischemic injury
TLR3 ligand preconditioning and cerebral ischemic injury
TLR4 ligand preconditioning and cerebral ischemic injury
TLR7 ligand preconditioning and cerebral ischemic injury
TLR8 ligand preconditioning and cerebral ischemic injury
TLR9 ligand preconditioning and cerebral ischemic injury
Mechanism of the protection against cerebral ischemia by TLR preconditioning
TLR ligand postconditioning and cerebral ischemic injury
Animal
|
Model
|
Postconditioning time/approach
|
TLR/ischemia
|
Results/mechanism
|
Author
|
References
|
---|---|---|---|---|---|---|
Mice | MCAO, ischemia 2 h | CCA 10-s ligation, subsequently 30-s open, a total of 3 cycles | Ischemic postconditioning | Decrease brain infarction volume and improve neurological function. Activate AKT signaling pathway | Gao X | [92] |
Mice | MCAO, 60-min ischemia, 24-h reperfusion | 30 min/systemic injection | TLR2, Pam3CSK4 | Decrease brain infarction volume and improve neurological function. Activate TLR2/PI3K/Akt signaling pathway | Lu C | [65] |
Mice | MCAO, 60-min ischemia, 24-h reperfusion | 30 min/IP | TLR3 poly-IC | Decrease brain infarction and prevention of Fas/FADD interaction | Zhang X | [67] |
Mice | MCAO, 60-min ischemia, 48-h reperfusion | 3 h/IP | TLR3 poly-IC | Decrease brain infarction volume and improve neurological function. Downregulate TLR4 signaling pathway by TLR3 | Wang PF | [90] |
Mice | MCAO, 60-min ischemia, 24-h reperfusion | 15 min/IP | TLR9 CpG-ODN | Decrease brain infarction and activation of PI3K/Akt Signaling | Lu C | [78] |