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-kappa B (NF-kappa B) [SMD = -1.78; CIs (-2.67, -0.88); p = 0.0)], and tumor necrosis factor alpha (TNF-alpha) [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-kappa B/TNF-alpha 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.