Department of Physical Therapy, College of Healthcare Medical Science & Engineering, Gimhae, Korea.
Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea.
CNS Neurosci Ther. 2022 Aug;28(8):1168-1182. doi: 10.1111/cns.13851. Epub 2022 May 5.
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.
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.
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].
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.
Toll 样受体（TLR）激动剂聚肌苷酸-聚胞苷酸（poly I:C）对脑缺血（CI）具有神经保护作用，但具体作用机制尚不清楚。
通过评估脑梗死体积（BIV）、神经功能缺损评分（N.S.）和信号通路蛋白等 CI 指标，评估 poly I:C 的神经保护作用。此外，我们进行了叙述性综述，以说明 TLR 的作用机制及其在 CI 中的作用。我们的搜索确定了 164 篇文章，其中 10 篇符合纳入标准。
poly I:C 降低 BIV 和 N.S.（p=0.00 和 p=0.03）。有趣的是，预处理和后处理均降低 BIV（预处理 p=0.04 和后处理 p=0.00）和 N.S.（预处理 p=0.03 和后处理 p=0.00）。此外，poly I:C 上调 TLR3 [SMD=0.64；CI（0.56，0.72）；p=0.00]，下调核因子-κB（NF-κB）[SMD=-1.78；CI（-2.67，-0.88）；p=0.0]，下调肿瘤坏死因子-α（TNF-α）[SMD=-16.83；CI（-22.63，-11.02）；p=0.00]。
我们表明 poly I:C 具有神经保护作用，作用机制是通过 TLR3/NF-κB/TNF-α 通路。我们的综述表明，抑制 TLR2/4 可能会对 CI 产生神经保护作用。进一步研究 poly I:C 同时激活 TLR3 和抑制 TLR2/4 可能为开发针对 CI 的治疗方法开辟新的前景。
