title: Hematopoietic cytokines--on the verge of conquering neurology.
abstract: Two hematopoietic cytokines are currently gaining increasing attention within neurological research. Erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) have long been known for their ability to induce the proliferation of certain populations of hematopoietic lineage cells. However, it has recently been found that EPO, G-CSF, and their respective receptors are also expressed in the human central nervous system (CNS) and may be an important part of the brain's endogenous system of protection. Both hematopoietic cytokines have been shown to have neuroprotective potential in a variety of animal disease models both in vitro and in vivo, through the inhibition of apoptosis, induction of angiogenesis, exertion of anti-inflammatory and neurotrophic effects, as well as by the enhancement of neurogenesis. EPO and G-CSF have been extensively studied in the context of hematological disorders and have recently been successfully applied in the first clinical trials in stroke patients. Intravenous high-dose EPO therapy was associated with an improvement in the clinical outcome and preclinical studies with intravenous high-dose G-CSF therapy have clearly shown that it has considerable neuroprotective potential in the acute, as well as in the chronic phase of stroke. In this review, the current knowledge of the neuroprotective mechanisms of EPO and G-CSF is summarized with regard to in vitro and in vivo data. Focus is placed on the role of EPO in neurological disease models with an emphasis on its influence on functional outcome. New experimental results are assessed in detail and correlated with the findings of recent clinical studies.
authors.affiliation: Deptartment of Neurology, Georg-August-University Göttingen, Faculty of Medicine, S1-Laboratory, Waldweg 33, 37073 Göttingen, Germany. ltoenge@gwdg.de
authors.forename: Lars
authors.initials: L
authors.lastname: Tönges
authors.forename: Johannes C M
authors.initials: JC
authors.lastname: Schlachetzki
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Weishaupt
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000502:physiology*; D004921:Erythropoietin / Q000494:pharmacology / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D008959:Models, Neurological; D018919:Neovascularization, Physiologic; D009422:Nervous System Diseases / Q000188:drug therapy; D009462:Neurology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy; D012107:Research Design; D015398:Signal Transduction; D020521:Stroke / Q000188:drug therapy
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor