The Role of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Brain Repair during Chronic Stroke

Abstract

Chronic stroke is a highly important but under-investigated scientific problem in neurologic research. We have reported earlier that stem cell factor (SCF) in combination with granulocyte-colony stimulating factor (G-CSF) treatment during chronic stroke improves functional outcomes. Here we have determined the contribution of bone marrow-derived cells in angiogenesis and neurogenesis, which are enhanced by SCF+G-CSF treatment during chronic stroke. Using bone marrow tracking, flow cytometry, 2-photon live brain imaging, and immunohistochemistry, we observed that the levels of circulating bone marrow stem cells (BMSCs) (CD34+/c-kit+) were significantly increased by SCF+G-CSF treatment. In addition, live brain imaging revealed that numerous bone marrow-derived cells migrate into the brain parenchyma in the treated mice. We also found that bone marrow-derived cells, bone marrow-derived endothelial cells, vascular density, and bone marrow-derived neurons were significantly augmented by SCF+G-CSF. It is interesting that, in addition to the increase in bone marrow-derived endothelial cells, the number of bone marrow-derived pericytes was reduced after SCF+G-CSF treatment during chronic stroke. These data suggest that SCF+G-CSF treatment can enhance repair of brain damage during chronic stroke by mobilizing BMSCs, and promoting the contribution of bone marrow-derived cells to angiogenesis and neurogenesis.

NF-κB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke

“…Our previous work revealed that SCF + G-CSF treatment in chronic stroke increased the blood vessel density in the cortex adjacent to the infarct cavity (Piao et al, 2009). Stoltz et al (1996) reported that NF-κB crucially regulated angiogenesis.…”

“…We have demonstrated that systemic administration of SCF + G-CSF in the chronic phase of stroke enhances neuronal activity in the ipsilesional somatosensorimotor cortex and induces a stable and long-lasting functional improvement when compared to SCF or G-CSF alone (Zhao et al, 2007). Moreover, SCF + G-CSF treatment in chronic stroke also promotes neuronal network remodeling and blood vessel formation in the peri-infarct cortex Piao et al, 2009). However, how SCF + G-CSF treatment rebuilds neuronal and vascular networks in the chronic stroke brain remains unclear.…”

“…The procedures for this model have been described elsewhere (Piao et al, 2009). Briefly, after anesthetizing with Avertin (0.4 g/kg, i.p.)…”

Effects of Granulocyte-Colony Stimulating Factor After Stroke in Aged Rats

“…18 Likewise, administration of G-CSF alone or in combination with stem cell factor during chronic stroke improves functional outcomes, possibly by facilitating the proliferation of endogenous neural stem cells and enhancing cytokine-induced generation of neuronal cells from bone marrow-derived cells. 19,20 G-CSF treatment was recently shown to induce substantially more neural progenitor cells and immature neurons in subcortical regions adjacent to the infarcted area. G-CSF also increased neurogenesis in the dentate gyrus of the hippocampus.…”

The Possible Roles of Brain Pericytes in Brain Ischemia and Stroke

“…They may also originate from the immature cells in the local environment in the brain. Pericytes are considered to possess multipotent activity and are able to differentiate into different lineages similar to MSCs (Piao et al 2009). Pericytes may promote tissue repair by a balance between active angiogenesis under scarce pericytes and vessel maturation by rich pericyte coverage.…”