Effect of Combination Therapy Using Hypothermia and Granulocyte Colony-Stimulating Factor in a Rat Transient Middle Cerebral Artery Occlusion Model

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.

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Effect of Combination Therapy Using Hypothermia and Granulocyte Colony-Stimulating Factor in a Rat Transient Middle Cerebral Artery Occlusion Model

Cited by 7 publications

References 30 publications

Neuroprotective effect of ethanol and Modafinil on focal cerebral ischemia in rats

Neuroprotective effect of ethanol and Modafinil on focal cerebral ischemia in rats

A Systematic Review and Meta-Analysis of Therapeutic Hypothermia and Pharmacological Cotherapies in Animal Models of Ischemic Stroke

The Protective and Reparative Role of Colony-Stimulating Factors in the Brain with Cerebral Ischemia/Reperfusion Injury

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