Effects of granulocyte colony-stimulating factor on focal cerebral ischemia- reperfusion injury in rats

Abstract

Abstract: Objective To study the therapeutic effects of granulocyte colony-stimulating factor (G-CSF) on focal cerebral ischemia-reperfusion injury in rats.Methods Adult male SD rats were subjected to transient (2 h) middle cerebral artery occlusion (MCAO) and scored 48 h later for such neurological functions as spontaneous movement, paresis, forelimb motor function, climbing ability, pain sensation, and position sense. Twenty rats with the total score less than 12 were divided equally into two groups to receive daily subcutaneous injection of 20 μg/kg of G-CSF for 19 days or the same dose of saline injection (control group). The rats in the two groups were also given intraperitoneal injection of Brdu10 mg/kg for 19 days. The neurological functions of the rats in both groups were examined on a weekly basis after MCAO and on day 21, the rats were killed to prepare frozen sections of the brain tissues for double immunohistochemical staining with Brdu and glial fibrillary acidic protein antibody to identify the neural cells newly evolved from the stem cells.Results The rats in G-CSF group showed better neurological function recovery than the control rats 3 weeks after MCAO (P<0.05). Obvious regeneration of the neural cells was observed around the infarction area in the rats receiving G-CSF treatment.Conclusion G-CSF promotes neurological function recovery and neural cell regeneration after cerebral infarction in rats and can be effective for intervention of focal cerebral ischemia-reperfusion injury.

CLC Number:

Q254
R651.1

CHEN Song-lin, ZHANG Cheng, HUANG Wen, YAO Xiao-li. Effects of granulocyte colony-stimulating factor on focal cerebral ischemia- reperfusion injury in rats[J]. Journal of Southern Medical University, 2005, 25(05): 503-507.

References

[1] Gould E, Reeves AJ, Grazano MS, et al. Neurogenesis in the neocortex of adult primates [J]. Science, 1999, 286(27): 548-52.
[2] Kuhn HG, Winkler J, Kempermann G, et al. Epidermal growth factor and fibroblast growth factor-2 have different effects on neura progenitors in the adult brain[J]. J Neurosci, 1997, 17(9): 5820-9.
[3] Park KI. Transplantation of neural stem cell: cellular and gene therapy for hypoxic ischmic brain injury [J]. Yonsei Med J, 2000, 41 (6):825-35.
[4] Nagasawa H, Kogure K. Correlation between cerebral blood and histologic change in a new rat model of cerebral artery occlusion [J]. Stroke, 1989, 20(6): 1037-41.
[5] Garcia JH. Waner S, Liu KF, et al. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats statistical validation. [J]. Stroke, 1995, 26(4): 627-34.
[6] 陈松林,张成,黄文,等.骨髓干细胞移植治疗Duchenne型肌营养不良鼠的实验研究[J].中华神经科杂志,2003,36(6):443-6.Chen SL, Zhang C, Huang W, et al. Duchenne muscular dystrophic mice treated by bone marrow stem cells transplantation [J]. Chin J Neurol, 2003, 36(6): 443-6.
[7] Abe K. Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury [J]. J Cereb Blood Flow Metab,2000, 20(10): 1393-408.
[8] 路艳蒙,傅文玉,朴英杰人骨髓间充质于细胞的培养及性质鉴定[J].第一军医大学学报,2001,21(8):571-3.Lu YM, Fu WY, Piao YJ. In vitro culture and identification of human bone marrow mesenchymal stem cell [J]. J First Mil Med Univ/Di Yi Jun Yi Da Xue Xue Bao, 2001, 21(8): 571-3.
[9] Eglitis MA, Mezey E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice [J]. Proc Natl Acad Sci USA, 1997, 94(67): 4080-5.
[10] 林竞韧,郭坤元,李江琪,等.人骨髓基质干细胞克隆的培养及其向神经元样细胞的定向诱导分化[J].第一军医大学学报,2003,23(3):251-5Lin JR, Guo KY, Li JQ, et al. In vitro culture of human bone marrow mesenchymal stem cell clonies and induced differentiation into neuron-like cells [J]. J First Mil Med Univ/Di Yi Jun Yi Da Xue Xue Bao, 2003, 23(3): 251-5.
[11] Chen JL, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats [J]. Stroke, 2001, 32(29): 1005-11.
[12] Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac fuction[J]. Nat Med, 2001, 7(4): 430-6.
[13] Park KI. Transplantation of neural stem cell: cellular and gene therapy for hypoxic ischmic brain injury[J]. Yonsei Med J, 2000,41(6): 825-35.
[14] Mampalam TJ, Gonzalez MF, Weinstein P, et al. Neuronal changes in fetal cortex transplanted to ischemic adult rat cortex [J]. J Neurosurg, 1998, 69(53): 904-12.
[15] Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development ofa neurologic examination[J]. Stroke, 1986, 17(13): 472-6.
[16] De Ryck M, Reempts JV, Borgers M, et al. Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats[J]. Stroke, 1989, 20(17): 1383-90.
[17] Jiang W, Gu WG, Brannstrom T, et al. Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion [J]. Stroke,2001, 32(27): 1201-7.
[18] 张卉,王纪佐,孙红宇,等.诱导成人骨髓基质细胞成为神经干细胞及其分化的实验研究[J].中风与神经疾病杂志,2002,19(2):79-82Zhang H, Wang JZ, Sun HY, et al. Induction of human bone marrow stromal cells to neural stem cells and neural cells in vitro [J].Apoplexy Nerv Dis, 2002, 19(2): 79-82.
[19] Cheng H, Wu JP, Zeng SF. Neuroprotetion of glial cell line-derived neurotropic factor in damaged spinal cords following contusive injury[J]. J Neurosci Res, 2002, 69(3): 397-405..
[20] Jin K, Mao XO, Sun YJ, et al. Stem cell factor stimulates neurogenesis in vitro and in vivo[J]. J Clin Invest, 2002, 110(89): 311-9.
[21] Yagita Y, Kitagawa K, Ohtsuki T, et al. Neurogenesis by progenitor Ccells in the ischemic adult rat hippocampus [J]. Stroke, 2001, 32(30): 1890-6.
[22] Six I, Gasan G, Mura E, et al. Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia [J].Eur J Pharmaco12003, 458(3): 327-8.
[23] Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia[J]. Stroke, 2003, 34: 745.
[24] Cavallaro AM, Lilleby K, Majolino I, et al. Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor [J]. Bone Marow Transplant,2000, 25(13): 85-9.