Sharif Ayni, Jeffers Matthew S, Fergusson Dean A, Bapuji Raj, Nicholls Stuart G, Humphrey John, Johnston Warren, Mitchell Ed, Speirs Mary-Ann, Stronghill Laura, Vuckovic Michele, Wulf Susan, Shorr Risa, Dowlatshahi Dar, Corbett Dale, Lalu Manoj M
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, Canada.
School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada.
Elife. 2025 Apr 7;14:RP103245. doi: 10.7554/eLife.103245.
C-C chemokine receptor type 5 (CCR5) antagonists may improve both acute stroke outcome and long-term recovery. Despite their evaluation in ongoing clinical trials, gaps remain in the evidence supporting their use. With a panel of patients with lived experiences of stroke, we performed a systematic review of animal models of stroke that administered a CCR5 antagonist and assessed infarct size or behavioural outcomes. MEDLINE, Web of Science, and Embase were searched. Article screening and data extraction were completed in duplicate. We pooled outcomes using random effects meta-analyses. We assessed risk of bias using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool and alignment with the Stroke Treatment Academic Industry Roundtable (STAIR) and Stroke Recovery and Rehabilitation Roundtable (SRRR) recommendations. Five studies representing 10 experiments were included. CCR5 antagonists reduced infarct volume (standard mean difference -1.02; 95% confidence interval -1.58 to -0.46) when compared to stroke-only controls. Varied timing of CCR5 administration (pre- or post-stroke induction) produced similar benefit. CCR5 antagonists significantly improved 11 of 16 behavioural outcomes reported. High risk of bias was present in all studies and critical knowledge gaps in the preclinical evidence were identified using STAIR/SRRR. CCR5 antagonists demonstrate promise; however, rigorously designed preclinical studies that better align with STAIR/SRRR recommendations and downstream clinical trials are warranted. Prospective Register of Systematic Reviews (PROSPERO CRD42023393438).
C-C趋化因子受体5（CCR5）拮抗剂可能会改善急性中风的预后和长期恢复情况。尽管它们正在进行临床试验评估，但支持其使用的证据仍存在差距。我们与一组有中风亲身经历的患者合作，对给予CCR5拮抗剂并评估梗死面积或行为结果的中风动物模型进行了系统评价。检索了MEDLINE、科学网和Embase。文章筛选和数据提取由两人独立完成。我们使用随机效应荟萃分析汇总结果。我们使用实验动物系统评价中心（SYRCLE）工具评估偏倚风险，并与中风治疗学术产业圆桌会议（STAIR）和中风恢复与康复圆桌会议（SRRR）的建议进行比对。纳入了代表10项实验的5项研究。与仅患有中风的对照组相比，CCR5拮抗剂减少了梗死体积（标准平均差-1.02；95%置信区间-1.58至-0.46）。CCR5给药的不同时间（中风诱导前或后）产生了类似的益处。在报告的16项行为结果中，CCR5拮抗剂显著改善了11项。所有研究均存在高偏倚风险，并且使用STAIR/SRRR确定了临床前证据中的关键知识空白。CCR5拮抗剂显示出前景；然而，需要严格设计的临床前研究，使其更好地符合STAIR/SRRR建议，并开展下游临床试验。系统评价前瞻性注册库（PROSPERO CRD42023393438）。
