New targets for established proteins: exploring G-CSF for the treatment of stroke.
Several recent reports describe the efficacy of the hematopoietic factor granulocyte-colony-stimulating factor (G-CSF) in models of stroke and neurodegeneration. Here, we discuss the role of G-CSF as a novel type of multifactorial drug with which to treat stroke, and describe aspects of its modes of action in stroke, in addition to the relationship between clinical trials and the preclinical dataset. Neuroprotective activity in stroke models seems to be based on a direct anti-apoptotic activity in neurons that is mediated by the neuronally expressed G-CSF receptor. Explanations for the long-term effects that improve recovery in different experimental models of stroke include the enhancement of neurogenesis in the adult brain and the stimulation of blood vessel formation. Additional beneficial effects might be based on systemic influences on immunocompetence and inflammation parameters, and the activation of bone-marrow-derived stem cells. Several clinical trials have been initiated in stroke patients, mainly to demonstrate the safety of G-CSF in this setting.
Schäbitz
Wolf-Rüdiger
WR
Department of Neurology, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. schabitz@uni-muenster.de
Schneider
Armin
A
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy; D002986:Clinical Trials as Topic; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D020521:Stroke / Q000188:drug therapy*
D016179:Granulocyte Colony-Stimulating Factor