Stroke is a debilitating disease and has the ability to culminate in devastating clinical outcomes. Ischemic stroke followed by reperfusion entrains cerebral ischemia / reperfusion (I/R) injury, which is a complex pathological process and is associated with serious clinical manifestations. Therefore, the development of a robust and effective post-stroke therapy is crucial. Granulocyte colony stimulating factor (GCSF) and erythropoietin (EPO), originally discovered as hematopoietic growth factors, are versatile and have transcended beyond their traditional role of orchestrating the proliferation, differentiation and survival of hematopoietic progenitors to one that fosters brain protection/ neuroregeneration. The clinical indication regarding GCSF and EPO as an auspicious therapeutic strategy is conferred in a plethora of illnesses, including anemia and neutropenia. EPO and GCSF alleviate cerebral I/R injury through a multitude of mechanisms, involving anti-apoptotic, anti-inflammatory, antioxidant, neurogenic and angiogenic effects. Despite bolstering evidence from preclinical studies, the multiple brain protective modalities of GCSF and EPO failed to translate in clinical trials and thereby raises several questions. The present review comprehensively compiles and discusses key findings from in vitro, in vivo and clinical data pertaining to the administration of EPO, GCSF, and other drugs which alter levels of colony stimulating factor (CSF) in the brain following cerebral I/R injury and elaborates on the contributing factors which led to the lost in translation of CSFs from bench to bedside. Any controversial findings are discussed to enable a clear overview of the role of EPO and GCSF as robust and effective candidates for post-stroke therapy.


中文翻译：

---

集落刺激因子在脑缺血/再灌注损伤中的保护和修复作用

中风是一种使人衰弱的疾病，并有能力最终导致毁灭性的临床结果。缺血性脑卒中继发再灌注引起脑缺血/再灌注（I/R）损伤，这是一个复杂的病理过程，与严重的临床表现有关。因此，开发稳健有效的卒中后治疗至关重要。粒细胞集落刺激因子 (GCSF) 和促红细胞生成素 (EPO) 最初是作为造血生长因子被发现的，它们用途广泛，已经超越了它们协调造血祖细胞增殖、分化和存活的传统作用，成为促进大脑保护/神经再生的作用。将 GCSF 和 EPO 作为一种吉祥的治疗策略的临床适应症被赋予了过多的疾病，包括贫血和中性粒细胞减少症。EPO 和 GCSF 通过多种机制减轻脑 I/R 损伤，包括抗凋亡、抗炎、抗氧化、神经源性和血管生成作用。尽管有临床前研究的证据，但 GCSF 和 EPO 的多种脑保护方式未能在临床试验中转化，从而引发了几个问题。本综述全面汇编和讨论了与 EPO、GCSF 和其他可改变脑 I/R 损伤后脑中集落刺激因子 (CSF) 水平的药物有关的体外、体内和临床数据的主要发现和详细阐述了导致 CSF 从工作台到床边的翻译过程中丢失的促成因素。