Brain Repair by Hematopoietic Growth Factors in a Rat Model of Stroke

Abstract

Background and Purpose— Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are essential growth factors in hematopoiesis. We determined whether receptors for SCF and G-CSF exist in the brain and whether exogenous SCF and G-CSF are beneficial to brain repair after brain ischemia. Methods— A well-established rat model of experimental stroke was used in this study. SCF, G-CSF, SCF+G-CSF, or saline was subcutaneously administered 3 hours to 7 days after brain ischemia. Bromodeoxyuridine was administered simultaneously. Sensorimotor function was evaluated with a limb placement test and foot fault test over time. Results— We observed that receptors for SCF and G-CSF were expressed in both neurogenic regions and neurons. SCF-treated rats showed the best functional restoration at 1 week that was maintained 4, 7, and 10 weeks after the final injection. G-CSF-induced functional recovery was limited and unstable. Interestingly, stable but delayed functional improvement was seen in SCF+G-CSF-treated rats. Infarction size was significantly reduced in all growth factor-treated rats. In addition, SCF and SCF+G-CSF enhanced neural progenitor cell proliferation in the subventricular zone bilaterally, whereas G-CSF and SCF+G-CSF treatment increased bromodeoxyuridine -positive cells in periinfarct areas. Conclusions— SCF and G-CSF are neuroprotective and beneficial to functional restoration when administered during the acute phase after brain ischemia, indicating hematopoietic growth factors play a role in brain repair.

Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia

“…However, our analysis showed that only 1 study 33 investigated G-CSF efficacy in animals with a comorbidity (hypertension), whereas no studies investigated G-CSF in stroke models with other conditions such as diabetes or high age. This lack of information should certainly be addressed in future studies.…”

Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy

“…G-CSF is an essential growth factor in hematopoiesis and may play a role in brain repair. It is neuroprotective and beneficial to functional restoration when administered after brain ischemia (45) and may also have significant neuroprotective effects on motoneuron cell lines in models of ALS (46). A pilot study of G-CSF mobilization of peripheral blood stem cells in ALS has been conducted, under the hypothesis that transiently increasing the number of circulating hematopoietic stem cells might be beneficial in treatment of this disease (47).…”

Granulocyte-colony stimulating factor in experimental stroke and its effects on infarct size and functional outcome: A systematic review

“…The majority of included studies were randomised (Gibson et al, 2005a;Gibson et al, 2005b;Han et al, 2008;Komine-Kobayashi et al, 2006;Lan et al, 2008;Lee et al, 2005;Schabitz et al, 2003;Schneider et al, 2005; Yanqing et al, 2006;Zhao et al, 2007c) and although each study varied in G-CSF dose regimen, only one study specifically addressed the optimal time window of drug administration (Lee et al, 2005). One study assessed dose response (Taguchi et al 2007).…”