Granulocyte colony-stimulating factor improves neurological function and angiogenesis in intracerebral hemorrhage rats

Objective: Granulocyte colony-stimulating factor (G-CSF) plays a role in regulating phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K/Akt) pathway, affecting cell proliferation and Apoptosis, and inducing vascular endothelial growth factor (VEGF) expression. This study investigated the mechanism of G-CSF on angiogenesis and neural protection after intracerebral hemorrhage (ICH).

Materials and methods: The rats were divided into four groups, including sham, ICH, ICH+G-CSF, and ICH+G-CSF+LY294002 (PI3K/Akt signaling pathway specific inhibitor). Cerebral neurological dysfunction was tested by Garcia scoring. Cell Apoptosis was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Angiogenesis marker CD34 expression, PI3K/Akt signaling pathway, B-cell lymphoma-2 (Bcl-2), and VEGF expressions were compared by IHC. Rat cerebral nerve RN-c cells were divided into four groups, including control, oxygen-glucose deprivation (OGD), OGD+G-CSF, and OGD+G-CSF+LY294002.

Results: Neurological dysfunction was more evident; CD34+ cell number, VEGF expression, and cell Apoptosis significantly increased; phosphorylated Akt (p-AKT) and Bcl-2 levels markedly reduced in ICH group compared with sham group. G-CSF apparently up-regulated p-AKT and Bcl-2 expressions, attenuated cell Apoptosis, and elevated CD34+ cell number. LY294002 significantly decreased p-AKT, Bcl-2, and VEGF expressions, and alleviated the cell Apoptosis protective and angiogenesis effect induced by G-CSF. OGD treatment induced RN-c cell Apoptosis, down-regulated p-AKT and Bcl-2 expressions, and enhanced the tube capacity of vascular endothelial cells (VEC). G-CSF markedly elevated p-AKT and Bcl-2 contents in RN-c cells, declined cell Apoptosis, increased p-AKT and VEGF levels in VEC, and enhanced tube capacity.

Conclusions: G-CSF enhanced PI3K/Akt signaling pathway activity, promoted Bcl-2 and VEGF expression, reduced nerve cell Apoptosis, and enhanced tube capacity of VECs, which may be the mechanism of G-CSF in improving neurological function and angiogenesis after ICH.