Pre‐ and post‐conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta‐analysis

Background Toll‐like receptor (TLR) agonist polyinosinic–polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear. Methods We evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion. Results Poly I:C reduces BIV and N.S. ( p  = 0.00 and p  = 0.03). Interestingly, both pre‐ and post‐conditioning decrease BIV (preC p  = 0.04 and postC p  = 0.00) and N.S. (preC p  = 0.03 and postC p  = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p  = 0.00], downregulates nuclear factor‐κB (NF‐κB) [SMD = −1.78; CIs (−2.67, −0.88); p  = 0.0)], and tumor necrosis factor alpha (TNF‐α) [SMD = −16.83; CIs (−22.63, −11.02); p  = 0.00]. Conclusion We showed that poly I:C is neuroprotective and acts via the TLR3/NF‐κB/TNF‐α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.