粒细胞集落刺激因子对大鼠脑出血模型的保护作用
|
摘要
中风是全球成年人致死性疾病的第三位，并长期位于成年人致残性疾病的首位。脑出血(ICH)约占西方人群中所有中风性疾病的10-15％，在亚洲人群中比例更高，至少达到30％。生长因子是一类参与调节神经细胞生存、增殖、分化发育的多肽。很多生长因子在脑创伤或中风后给药都显示出神经保护和神经营养作用。
粒细胞集落刺激因子(G-CSF)是生长因子类细胞因子的一员，分子量约20KD。粒细胞集落刺激因子现已广泛的应用于临床，包括肿瘤化疗所致的白细胞减少症、骨髓的重构、造血干细胞的募集等。近年来研究发现，一些中风模型的造模小鼠给予粒细胞集落刺激因子后可诱导受损脑组织周围的神经发生，最终促进小鼠神经功能的恢复。但粒细胞集落刺激因子在脑出血过程中是否扮演相同角色尚未见报道。
本研究试图探讨粒细胞集落刺激因子在脑出血中是否具有神经保护作用。我们选择健康wistar雄性大鼠40只，分为阴性对照组(20只)和G-CSF治疗组(20只)，全部进行脑出血模型造模。我们采用胶原酶Ⅶ定位注射大鼠尾壳核诱导大鼠脑出血的方法复制脑出血模型。造模24小时后G-CSF治疗组进行腹腔注射G-CSF(15μg／kg)，连续治疗5天，对照组给予生理盐水。我们每周通过肢体放置实验检测大鼠神经功能恢复情况，连续观察4周后发现，给药组可以明显促进脑出血大鼠神经功能的恢复。
为了探讨G-CSF促进脑出血大鼠神经功能恢复的机制，我们用免疫组化的方法检测了脑片的三个指标，分别为神经干细胞标志nestin，造血干细胞标志CD34和星形胶质细胞标志GFAP，还通过Hoechest33258荧光显色的方法检测了脑出血大脑半球的细胞凋亡情况。最后，我们测量了出血坏死区病灶的面积。
实验结果显示：
1．G-CSF可促进出血灶周边组织神经干细胞的表达。
2．G-CSF可动员骨髓造血干细胞入脑参与神经修复。
3．G-CSF可增强脑出血后星形胶质细胞的增殖。
4．G-CSF有抗凋亡的作用。
5．两组大鼠的病灶面积未见明显差异。
综上所述，我们的研究证实粒细胞集落刺激因子可促进脑出血大鼠神经功能的恢复，其机制可能与粒细胞集落刺激因子促进神经干细胞表达、动员造血干细胞入脑、刺激星形胶质细胞增殖以及其抗凋亡作用均有关系，但其具体机制仍需进一步深入研究揭示。
Stroke is the third leading cause of death and a leading cause of long-term disability inadults worldwide.Intracerebral hemorrhage (ICH) represents 10-15% of all strokes in theWestern population and at least 30% in Asian countries.Growth factors are polypeptideswhich regulate survival,proliferation,maturation of developing neuronal cells.Manyfactors display endogenous neuroprotective and neurotrophic effects when they areexogenously administrated after brain trauma or stroke.
Granulocyte colony-stimulating factor (G-CSF),is a member of the cytokine family ofgrowth factors.G-CSF has been used extensively in the treatment of chemotherapy-inducedneutropenia,as well as for bone marrow reconstitution and stem cell mobilization.Morerecently,it has been shown that administration of G-CSF in stroke mouse models couldinduce neurogenesis near the damaged area of these mice,leading to neurological andfunctional recovery.Until now,the role of G-CSF on ICH is not fully understood.
In the present study,we studied the potential neuroprotective effect of G-CSF in a ratmodel of ICH.For the induction of intracerebral hemorrhage and G-CSF treatment,maleWistar rats were grouped as ICH-only control group (n = 20) and G-CSF-treated ICH group(n = 20).Experimental ICH was induced by the stereotaxic administration of collagenasetypeⅦinto caudate nucleus.The recombinant human G-CSF (15μg/kg),dissolved innormal saline,was administered through intraperitoneal,at 24 h after the ICH induction anddaily afterwards for 5 days.The same volume of normal saline was adminstrated to theICH-only control group.The limb placement tests were examined weekly for 4 weeks afterintracerebral hemorrhage was induced.We found that intraperitoneal injection of G-CSF for5 days could efficiently attenuate the ICH-induced neuronal behavioral impairment.
To study the possible mechanisms underlying the behavioral improvement by G-CSF,we measured the expression of nestin,CD34 and GFAP by immunohistochemistry.We alsoobserved apoptosis by the immunofluorescence staining of Hoechst33258 and measured the sizes of necrosis area.
The results are shown as follows:
1.G-CSF may stimulate the expression of neural stem cells in the peri-necrosis area ofthe hemorrhagic hemisphere in the rats.
2.G-CSF may stimulate HSCs to migrate into the brain regions through bloodcirculation after ICH induction.
3.G-CSF can promote proliferation of astrocytes.
4.G-CSF has anti-apoptotic effect after ICH.
5.No differences were found in the sizes of necrosis area between G-CSF-treatedgroup and control.
In summary,we have found in the present study that administration of G-CSF canimprove the ICH-induced neurobehavioral impairments in rats.The mechanism mayinvolve proliferation of neural stem cells;the mobilization of HSCs to damaged areas of thebrain;the increased astrocytes;and the anti-apoptotic effect of G-CSF.
粒细胞集落刺激因子(G-CSF)是生长因子类细胞因子的一员，分子量约20KD。粒细胞集落刺激因子现已广泛的应用于临床，包括肿瘤化疗所致的白细胞减少症、骨髓的重构、造血干细胞的募集等。近年来研究发现，一些中风模型的造模小鼠给予粒细胞集落刺激因子后可诱导受损脑组织周围的神经发生，最终促进小鼠神经功能的恢复。但粒细胞集落刺激因子在脑出血过程中是否扮演相同角色尚未见报道。
本研究试图探讨粒细胞集落刺激因子在脑出血中是否具有神经保护作用。我们选择健康wistar雄性大鼠40只，分为阴性对照组(20只)和G-CSF治疗组(20只)，全部进行脑出血模型造模。我们采用胶原酶Ⅶ定位注射大鼠尾壳核诱导大鼠脑出血的方法复制脑出血模型。造模24小时后G-CSF治疗组进行腹腔注射G-CSF(15μg／kg)，连续治疗5天，对照组给予生理盐水。我们每周通过肢体放置实验检测大鼠神经功能恢复情况，连续观察4周后发现，给药组可以明显促进脑出血大鼠神经功能的恢复。
为了探讨G-CSF促进脑出血大鼠神经功能恢复的机制，我们用免疫组化的方法检测了脑片的三个指标，分别为神经干细胞标志nestin，造血干细胞标志CD34和星形胶质细胞标志GFAP，还通过Hoechest33258荧光显色的方法检测了脑出血大脑半球的细胞凋亡情况。最后，我们测量了出血坏死区病灶的面积。
实验结果显示：
1．G-CSF可促进出血灶周边组织神经干细胞的表达。
2．G-CSF可动员骨髓造血干细胞入脑参与神经修复。
3．G-CSF可增强脑出血后星形胶质细胞的增殖。
4．G-CSF有抗凋亡的作用。
5．两组大鼠的病灶面积未见明显差异。
综上所述，我们的研究证实粒细胞集落刺激因子可促进脑出血大鼠神经功能的恢复，其机制可能与粒细胞集落刺激因子促进神经干细胞表达、动员造血干细胞入脑、刺激星形胶质细胞增殖以及其抗凋亡作用均有关系，但其具体机制仍需进一步深入研究揭示。
Stroke is the third leading cause of death and a leading cause of long-term disability inadults worldwide.Intracerebral hemorrhage (ICH) represents 10-15% of all strokes in theWestern population and at least 30% in Asian countries.Growth factors are polypeptideswhich regulate survival,proliferation,maturation of developing neuronal cells.Manyfactors display endogenous neuroprotective and neurotrophic effects when they areexogenously administrated after brain trauma or stroke.
Granulocyte colony-stimulating factor (G-CSF),is a member of the cytokine family ofgrowth factors.G-CSF has been used extensively in the treatment of chemotherapy-inducedneutropenia,as well as for bone marrow reconstitution and stem cell mobilization.Morerecently,it has been shown that administration of G-CSF in stroke mouse models couldinduce neurogenesis near the damaged area of these mice,leading to neurological andfunctional recovery.Until now,the role of G-CSF on ICH is not fully understood.
In the present study,we studied the potential neuroprotective effect of G-CSF in a ratmodel of ICH.For the induction of intracerebral hemorrhage and G-CSF treatment,maleWistar rats were grouped as ICH-only control group (n = 20) and G-CSF-treated ICH group(n = 20).Experimental ICH was induced by the stereotaxic administration of collagenasetypeⅦinto caudate nucleus.The recombinant human G-CSF (15μg/kg),dissolved innormal saline,was administered through intraperitoneal,at 24 h after the ICH induction anddaily afterwards for 5 days.The same volume of normal saline was adminstrated to theICH-only control group.The limb placement tests were examined weekly for 4 weeks afterintracerebral hemorrhage was induced.We found that intraperitoneal injection of G-CSF for5 days could efficiently attenuate the ICH-induced neuronal behavioral impairment.
To study the possible mechanisms underlying the behavioral improvement by G-CSF,we measured the expression of nestin,CD34 and GFAP by immunohistochemistry.We alsoobserved apoptosis by the immunofluorescence staining of Hoechst33258 and measured the sizes of necrosis area.
The results are shown as follows:
1.G-CSF may stimulate the expression of neural stem cells in the peri-necrosis area ofthe hemorrhagic hemisphere in the rats.
2.G-CSF may stimulate HSCs to migrate into the brain regions through bloodcirculation after ICH induction.
3.G-CSF can promote proliferation of astrocytes.
4.G-CSF has anti-apoptotic effect after ICH.
5.No differences were found in the sizes of necrosis area between G-CSF-treatedgroup and control.
In summary,we have found in the present study that administration of G-CSF canimprove the ICH-induced neurobehavioral impairments in rats.The mechanism mayinvolve proliferation of neural stem cells;the mobilization of HSCs to damaged areas of thebrain;the increased astrocytes;and the anti-apoptotic effect of G-CSF.
引文
1. Qureshi AL Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF (2001) Spontaneous intracerebral hemorrhage. N Engl J Med 344:1450-1460
2. Arvidsson A, Kokaia Z, Airaksinen MS, Saarma M, Lindvall O (2001) Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain. Neuroscience 106:27-41
3. Larsson E, Nanobashvili A, Kokaia Z, Lindvall O (1999) Evidence for neuroprotectiveeffects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats. J Cereb Blood Flow Metab 19:1220-1228
4. Mattson MP, Scheff SW (1994) Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy. J Neurotrauma 11:3-33
5. Semkova Ⅰ, Krieglstein J (1999) Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res Brain Res Rev 30:176-188
6. Schabitz WR, Hoffmann TT, Heiland S, Kollmar R, Bardutzky J, Sommer C, Schwab S (2001) Delayed neuroprotective effect of insulin-like growth factor-Ⅰafter experimental transient focal cerebral ischemia monitored with MRI. Stroke 32:1226-1233
7. Schabitz WR, Sommer C, Zoder W, Kiessling M, Schwaninger M, Schwab S (2000) Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke 31:2212-2217
8. Sheridan WP, Morstyn G, Wolf M, Dodds A, Lusk J, Maher D, Layton JE, Green MD, Souza L, Fox RM (1989) Granulocyte colony-stimulating factor and neutrophil recovery after high-dose chemotherapy and autologous bone marrow transplantation.Lancet 2:891-895
9. Weaver CH. Buckner CD, Longin K, Appelbaum FR, Rowley S, Lilleby K, Miser J, Storb R, Hansen JA, Bensinger W (1993) Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. Blood 82:1981-1984
10. Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, Li H (2004) Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110:1847-1854
11. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassier N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A, Kuhn HG, Schabitz WR (2005) The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 115:2083-2098
12. Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, Takagi S, Okano H, Ando K, Hotta T (2006) Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 113:701-710
13. Ohlsson AL, Johansson BB (1995) Environment influences functional outcome of cerebral infarction in rats. Stroke 26:644-649
14. Zhao LR, Duan WM, Reyes M, Keene CD, Verfailiie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11-20
15. Yanqing Z, Yu-Min L, Jian Q, Bao-Guo X, Chuan-Zhen L (2006) Fibronectin and neuroprotective effect of granulocyte colony-stimulating factor in focal cerebral ischemia. Brain Res 1098:161-169
16. Zhao LR, Berra HH, Duan WM, Singhal S, Mehta J, Apkarian AV, Kessler JA (2007) Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats. Stroke 38:2804-2811
17. Zhao LR, Singhal S, Duan WM, Mehta J, Kessler JA (2007) Brain repair by hematopoietic growth factors in a rat model of stroke. Stroke 38:2584-2591
18. Schabitz WR, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Scholzke MN,Sommer C, Schwab S (2003) Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 34:745-751
19. Sprigg N, Bath PM, Zhao L, Willmot MR, Gray LJ, Walker MF, Dennis MS, Russell N (2006) Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem cell Trial of recovery EnhanceMent after Stroke (STEMS) pilot randomized, controlled trial (ISRCTN 16784092). Stroke 37:2979-2983
20. Shyu WC, Lin SZ, Lee CC, Liu DD, Li H (2006) Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. CMA.T 174:927-933
21. Solaroglu I, Cahill J, Jadhav V, Zhang JH (2006) A novel neuroprotectant granulocyte-colony stimulating factor. Stroke 37:1123-1128
22. Dirnagl U, Simon RP, Hallenbeck JM (2003) Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 26:248-254.
23. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819-834.
24. Lachmund A, Gehrke D, Krieglstein K, Unsicker K (1994) Trophic factors from chromaffm granules promote survival of peripheral and central nervous system neurons.Neuroscience 62:361-370.
25. Williams LR, Varon S, Peterson GM, Wictorin K, Fischer W, Bjorklund A,Gage FH (1986) Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Natl Acad Sci U S A 83:9231-9235.
26. Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z,Kowalska MA, Gewirtz AM, Emerson SG, Ratajczak MZ (2001) Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 97:3075-3085
27. Cohen-Cory S, Fraser SE (1995) Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature 378:192-196.
28. Garofalo L, Ribeiro-da-Silva A, Cuello AC (1992) Nerve growth factor-induced synaptogenesis and hypertrophy of cortical cholinergic terminals. Proc Natl Acad Sci USA 89:2639-2643
29. Kang H, Schuman EM (1995) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267:1658-1662
30. Lindholm D (1997) Neurotrophic factors and neuronal plasticity: is there a link? Adv Neurol73:1-6.
31. Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229-237
32. Cotter DR, Pariante CM, Everall IP (2001) Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 55:585-595
33. Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563-581
34. Virgin CE Jr, Ha TP, Packan DR, Tombaugh GC, Yang SH, Homer HC, Sapolsky RM (1991) Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity. JNeurochem 57:1422-1428
35. Wilson JX (1997) Antioxidant defense of the brain; a role for astrocytes. Can J Physiol Pharmacol 75:1149-1163
36. Ritchie LJ, De Butte M, Pappas BA (2004) Chronic mild stress exacerbates the effects of permanent bilateral common carotid artery occlusion on CA1 neurons. Brain Res 1014:228-235
37. Wesselingh SL, Gough NM, Finlay-Jones JJ, McDonald PJ (1990) Detection of cytokine mRNA in astrocyte cultures using the polymerase chain reaction. Lymphokine Res 9:177-185
38. Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M (1990) Collagenase-induced intracerebral hemorrhage in rats. Stroke 21:801-807
39. Clark W, Gunion-Rinker L, Lessov N, Hazel K. (1998) Citicoline treatment for experimental intracerebral hemorrhage in mice. Stroke 29:2136-2140
40. Konishi Y, Chui DH, Hirose H, Kunishita T, Tabira T (1993) Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res 609:29-35
41. Longa EZ, Weinstein PR, Carlson S, et al (1989) Reversible middle cerebral artery exclusion without craniectomy in rats. Stroke 20:84-91
42. Hasselblatt M, Jeibmann A, Riesmeier B, Maintz D, Schabitz WR (2006 ) Granulocyte-colony stimulating factor (G-CSF) and G-CSF receptor expression in human ischemic stroke. Acta Neuropathol 113(1):45-51.
43. Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, Mochizuki H, Mizuno Y, Urabe T (2005) Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 127:
44. Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Sinn DI, Lee YS, Lo EH, Kim M, Roh JK (2005) Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res 1058:120-128
45. Sheibani N, Grabowski EF, Schoenfeld DA, Whalen MJ (2004) Effect of granulocyte colony-stimulating factor on functional and histopathologic outcome after traumatic brain injury in mice. Crit Care Med 32:2274-2278
46. Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C (1992) Production of hemolymphopoietic cytokines (IL-6,IL-8,colony-stimulatingfactors) by normal human astrocytes in response to IL-1(3 and tumor necrosis factor-a. J Immunol 149:2358-2366
47. Malipiero UV. Frei K, Fontana A (1990) Production of hemopoietic colony-stimulating factors by astrocytes. J Immunol 144:3816-3821
48. Boneberg EM, Hareng L, Gantner F, Wendel A, Hartung T (2000) Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-y. Blood 95:270-276
49. Budel LM, Touw IP, Delwel R, Lowenberg B (1989) Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia. Blood 74:2668-2673
50. Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P,Mantovani A (1989) Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 337:471-473
51. Hanazono Y, Hosoi T, Kuwaki T, Matsuki S, Miyazono K, Miyagawa K, Takaku F (1990) Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils. Exp Hematol 18:1097-1103
52. Morikawa K, Morikawa S, Nakamura M, Miyawaki T (2002) Characterization of granulocyte colony-stimulating factor receptor expressed on human lymphocytes. Br J Haematol 118:296-304
53. Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y (1993) Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 91:1310-1313
54. Fukunaga R, Ishizaka-Ikeda E, Pan CX, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10:2855-2865
1．Kaptanoglu E，Solaroglu I，Okutan O，Surucu HS，Akbiyik F，Beskonakli E (2004) Erythropoietin exerts neuroprotection after acute spinal cord injury in rats：effect on lipid peroxidation and early ultrastructural findings．Neurosurg Rev 27：113-120
2．Schabitz WR，Sommer C，Zoder W．Kiessling M，Schwaninger M，Schwab S (2000) Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebralischemia．Stroke 31：2212-2221
3．Solaroglu I，Solaroglu A，Kaptanoglu E，Dede S，Haberal A，Beskonakli E，Kilinc K (2003) Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain．Childs Nerv Syst 19：19-22
4．Ehrenreich H，Hasselblatt M．Dembowski C，Cepek L，Lewczuk P．Stiefel M，Rustenbeck HH，Breiter N，Jacob S，Knerlich F，Bohn M，Poser W，Ruther E，Kochen M，Gefeller O，Gleiter C，Wessel TC，De Ryck M，Itri L，Prange H，Cerami A，Brines M，Siren AL (2002) Erythropoietin therapy for acute stroke is both safe and beneficial．Mol Med 8：495-505
5．Demetri GD，Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor．Blood 78：2791-2808
6．Konishi Y，Chui DH，Hirose H，Kunishita T，Tabira T (1993) Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo．Brain Res 609：29-35
7．Gibson CL，Jones NC，Prior MJ，Bath PM．Murphy SP (2005) G-CSF suppresses edema formation and reduces interleukin-1βexpression after cerebral ischemia in mice．J Neuropathol Exp Neurol 64：763-769
8．Gibson CL，Bath PM，Murphy SP (2005) G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 25:431-439
9. Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, Mochizuki H, Mizuno Y, Urabe T (2005) Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 127:
10. Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Sinn DI, Lee YS, Lo EH, Kim M, Roh JK. (2005) Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res 1058:120-128
11. Schabitz WR, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Sholzke MN,Sommer C, Schwab S (2003) Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 34:745-751
12. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassier N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A,Kuhn HG, Schabitz WR. (2005) The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 15:2083-2098
13. Sheibani N, Grabowski EF, Schoenfeld DA, Whalen MJ (2004) Effect of granulocyte colony-stimulating factor on functional and histopathologic outcome after traumatic brain injury in mice. Crit Care Med 32:2274-2278
14. Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, Li H (2004) Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110:1847-1854
15. Six I, Gasan G, Mura E, Bordet R (2003) Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia. Eur J' Pharmacol 458:327-328
16. Wells JA, de Vos AM (1996) Hematopoieticr ecepto rcomplexes. Annu Rev Biochem 65:609-634
17. Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C (1992) Production of hemolymphopoietic cytokines (IL-6,IL-8,colony-stimulatingfactors) by normal human astrocytes in response to IL-1βand tumor necrosis factor-a. J Immunol 149:2358-2366
18. Malipiero UV, Frei K, Fontana A (1990) Production of hemopoietic colony-stimulating factors by astrocytes. J Immunol 144:3816-3821
19. Boneberg EM, Hareng L, Gantner F, Wendel A, Hartung T (2000) Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ. Blood 95:270-276
20. Budel LM, Touw IP, Delwel R, Lowenberg B (1989) Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia. Blood 74:2668-2673
21. Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P,Mantovani A (1989) Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 337:471-473
22. Hanazono Y, Hosoi T, Kuwaki T, Matsuki S, Miyazono K, Miyagawa K, Takaku F (1990) Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils. Exp Hematol 18:1097-1103
23. Morikawa K, Morikawa S, Nakamura M, Miyawaki T (2002) Characterization ofgranulocyte colony-stimulating factor receptor expressed on human lymphocytes. Br J Haematol 118:296-304
24. Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y (1993) Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 91:1310-1313
25. Fukunaga R, Ishizaka-Ikeda E, Pan CX, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10:2855-2865
26. Hunter MG, Avalos BR (1998) Phosphatidylinositol 3'-kinase and SH2-containing inositol phosphatase(SHIP) are recruited by distinct positive and negative growth-regulatory domains in the granulocyte colony-stimulating factor receptor. J Immunol 160:4979-4987
27. Shimoda K, Feng J, Murakami H, Nagata S, Watling D, Rogers NC, Stark GR, Kerr IM, Ihle JN (1997) Jakl plays an essential role for receptor phosphorylation and Stat activation in response to granulocyte colony-stimulating factor. Blood 90:597-604
28. Tian SS, Lamb P, Seidel HM, Stein RB, Rosen J (1994) Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood 84:1760-1764
29. Ward AC, Loeb DM, Soede-Bobok AA, Touw IP, Friedman AD (2000) Regulation of granulopoiesis by transcription factors and cytokine signals. Leukemia 14:973-990
30. Dong F, Lamer AC (2000) Activation of Akt kinase by granulocyte colony-stimulating factor(G-CSF):evidence for the role of a tyrosine kinase activity distinct from the Janus kinases. Blood 95:1656-1662
31. Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J, Storb R,Buckner CD (1995) Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 85:1655-1658
32. Carlsson G, Ahlin A, Dahllof G, Elinder G Henter JI, Palmblad JI (2004) Efficacy and safety of two different rG-CSF preparations in the treatment of patients with severe congenital neutropenia. Br J Haematol 126:127-132
33. Kocherlakota P, La Gamma EF (1997) Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia.Pediatrics 100:E6
34. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G (1996) Filgrastim(r-metHuG-CSF): the first 10 years. Blood 88:1907-1929
35. Kleinschnitz C, Schroeter M, Jander S, Stoll G (2004) Induction of granulocyte colony-stimulating factor mRNA by focal cerebral ischemia and cortical spreading depression. Brain Res Mol Brain Res 131:73-78
36. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke:new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819-834
37. Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391-397
38. Whalen MJ, Carlos TM, Wisniewski SR, Clark RS, Mellick JA, Marion DW,Kochanek PM (2000) Effect of neutropenia and granulocyte colony stimulating factor-induced neutrophilia on blood-brain barrier permeability and brain edema after traumatic brain injury in rats. Crit Care Med 28:3710-3717
39. Quagliarello VJ, Wispelwey B, Long WJ Jr, Scheld WM (1991) Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in therat.Characterization and comparison with tumor necrosis factor. J Clin Invest 87:1360-1366
40. Rosenman SJ, Shrikant P, Dubb L, Benveniste EN, Ransohoff RM (1995) Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. J Immunol 154:1888-1899
41. Zavala F, Abad S, Ezine S, Taupin V, Masson A, Bach JF (2002) G-CSF therapy o fongoing experimental allergic encephalomyelitis via chemokine-and cytokine-based immune deviation. J Immunol 168:2011-2019
42. Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, Frisch S,Reed JC (1998) Regulation of cell death protease caspase-9 by phosphorylation.Science 282:1318-1321
43. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G (1997) Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278:687-689
44. Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275:661-665
45. Fujio Y, Guo K, Mano T, Mitsuuchi Y, Testa JR., Walsh K (1999) Cell cycle withdrawal promotes myogenic induction of Akt,a positive modulator of myocytesurvival. Mol Cell Biol 19:5073-5082
46. Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE (2000) Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 275:10761-10766
47. Kim S, Jee K, Kim D, Koh H, Chung J (2001) Cyclic AMP inhibits Akt activity by blocking the membrane localization of PDK1. J Biol Chem 276:12864-12870
48. Liu L, Cavanaugh JE, Wang Y, Sakagami H, Mao Z, Xia Z (2003) ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons Proc Natl Acad Sci USA 100:8532-8537
49. Watson FL, Heerssen HM, Bhattacharyya A, Klesse L, Lin MZ, Segal RA (2001)Neurotrophins use the Erk5 pathway to mediate a retrograde survival response. Nat Neurosci 4:981-988
50. Tehranchi R, Fadeel B, Forsblom AM, Christensson B, Samuelsson J, Zhivotovsky B,Hellstrom-Lindberg E (2003) Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Blood 101:1080-1086
51. Wang L, Gang ZZ, Lan ZR, Chopp M (2005) Activation of the PI3-K/Ak pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricularzone. J Cereb Blood Flow Metab 2005:1150-1158
52. Katakowski M, Zhang ZG, Chen J, Zhang R, Wang Y, Jiang H, Zhang L, Robin A, Li Y,Chopp M (2003) Phosphoinositide 3-kinase promotes adult subventricular neuroblast migration after stroke. J Neurosci Res 74:494-501
53. Levesque JP, Hendy J, Takamatsu Y Simmons PJ, Bendall LJ (2003) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest 111:187-196
54. Peng H, Huang Y, Rose J, Erichsen D, Herek S, Fujii N, Tamamura H, Zheng J (2004) Stromal cell-derived factor1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells. J Neurosci Res 76:35-50
55. Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J,Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factorla/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101:18117-18122
56. Robin AM, Zhang ZG, Wang L, Zhang RL, Katakowski M, Zhang L, Wang Y, Zhang C,Chopp M (2006) Stromal cell-derived factor 1 mediates neural progenitor cell motility after focal cerebral ischemia. J Cereb Blood Flow Metab 26:125-134
57. Grigg AP, Roberts AW, Raunow H, Houghton S, Layton JE, Boyd AW, McGrath KM, Maher D (1995) Optimizing dose and scheduling of filgrastim(granulocyte colony-stimulating factor)for mobilization and collection of peripheral blood progenitor cells in normal volunteers. Blood 86:4437-4445
58. Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Hollt V, Schulz S (2002) A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain:Isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci 22:5865-5878
59. Khan M, Sekhon B, Giri S, Jatana M, Gilg AG, Ayasolla K, Elango C, Singh AK, Singh Ⅰ (2005) S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. J Cereb Blood Flow Metab 25:177-192
60. Lee H, Kim YO, Kim H, Kim SY, Noh HS, Kang SS, Cho GJ, Choi WS, SukK (2003) Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microslia. FASEB J 17:1943-1944
2. Arvidsson A, Kokaia Z, Airaksinen MS, Saarma M, Lindvall O (2001) Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain. Neuroscience 106:27-41
3. Larsson E, Nanobashvili A, Kokaia Z, Lindvall O (1999) Evidence for neuroprotectiveeffects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats. J Cereb Blood Flow Metab 19:1220-1228
4. Mattson MP, Scheff SW (1994) Endogenous neuroprotection factors and traumatic brain injury: mechanisms of action and implications for therapy. J Neurotrauma 11:3-33
5. Semkova Ⅰ, Krieglstein J (1999) Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res Brain Res Rev 30:176-188
6. Schabitz WR, Hoffmann TT, Heiland S, Kollmar R, Bardutzky J, Sommer C, Schwab S (2001) Delayed neuroprotective effect of insulin-like growth factor-Ⅰafter experimental transient focal cerebral ischemia monitored with MRI. Stroke 32:1226-1233
7. Schabitz WR, Sommer C, Zoder W, Kiessling M, Schwaninger M, Schwab S (2000) Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke 31:2212-2217
8. Sheridan WP, Morstyn G, Wolf M, Dodds A, Lusk J, Maher D, Layton JE, Green MD, Souza L, Fox RM (1989) Granulocyte colony-stimulating factor and neutrophil recovery after high-dose chemotherapy and autologous bone marrow transplantation.Lancet 2:891-895
9. Weaver CH. Buckner CD, Longin K, Appelbaum FR, Rowley S, Lilleby K, Miser J, Storb R, Hansen JA, Bensinger W (1993) Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. Blood 82:1981-1984
10. Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, Li H (2004) Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110:1847-1854
11. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassier N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A, Kuhn HG, Schabitz WR (2005) The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 115:2083-2098
12. Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, Takagi S, Okano H, Ando K, Hotta T (2006) Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 113:701-710
13. Ohlsson AL, Johansson BB (1995) Environment influences functional outcome of cerebral infarction in rats. Stroke 26:644-649
14. Zhao LR, Duan WM, Reyes M, Keene CD, Verfailiie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11-20
15. Yanqing Z, Yu-Min L, Jian Q, Bao-Guo X, Chuan-Zhen L (2006) Fibronectin and neuroprotective effect of granulocyte colony-stimulating factor in focal cerebral ischemia. Brain Res 1098:161-169
16. Zhao LR, Berra HH, Duan WM, Singhal S, Mehta J, Apkarian AV, Kessler JA (2007) Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats. Stroke 38:2804-2811
17. Zhao LR, Singhal S, Duan WM, Mehta J, Kessler JA (2007) Brain repair by hematopoietic growth factors in a rat model of stroke. Stroke 38:2584-2591
18. Schabitz WR, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Scholzke MN,Sommer C, Schwab S (2003) Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 34:745-751
19. Sprigg N, Bath PM, Zhao L, Willmot MR, Gray LJ, Walker MF, Dennis MS, Russell N (2006) Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem cell Trial of recovery EnhanceMent after Stroke (STEMS) pilot randomized, controlled trial (ISRCTN 16784092). Stroke 37:2979-2983
20. Shyu WC, Lin SZ, Lee CC, Liu DD, Li H (2006) Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. CMA.T 174:927-933
21. Solaroglu I, Cahill J, Jadhav V, Zhang JH (2006) A novel neuroprotectant granulocyte-colony stimulating factor. Stroke 37:1123-1128
22. Dirnagl U, Simon RP, Hallenbeck JM (2003) Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 26:248-254.
23. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819-834.
24. Lachmund A, Gehrke D, Krieglstein K, Unsicker K (1994) Trophic factors from chromaffm granules promote survival of peripheral and central nervous system neurons.Neuroscience 62:361-370.
25. Williams LR, Varon S, Peterson GM, Wictorin K, Fischer W, Bjorklund A,Gage FH (1986) Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Natl Acad Sci U S A 83:9231-9235.
26. Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z,Kowalska MA, Gewirtz AM, Emerson SG, Ratajczak MZ (2001) Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 97:3075-3085
27. Cohen-Cory S, Fraser SE (1995) Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature 378:192-196.
28. Garofalo L, Ribeiro-da-Silva A, Cuello AC (1992) Nerve growth factor-induced synaptogenesis and hypertrophy of cortical cholinergic terminals. Proc Natl Acad Sci USA 89:2639-2643
29. Kang H, Schuman EM (1995) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267:1658-1662
30. Lindholm D (1997) Neurotrophic factors and neuronal plasticity: is there a link? Adv Neurol73:1-6.
31. Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229-237
32. Cotter DR, Pariante CM, Everall IP (2001) Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 55:585-595
33. Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563-581
34. Virgin CE Jr, Ha TP, Packan DR, Tombaugh GC, Yang SH, Homer HC, Sapolsky RM (1991) Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity. JNeurochem 57:1422-1428
35. Wilson JX (1997) Antioxidant defense of the brain; a role for astrocytes. Can J Physiol Pharmacol 75:1149-1163
36. Ritchie LJ, De Butte M, Pappas BA (2004) Chronic mild stress exacerbates the effects of permanent bilateral common carotid artery occlusion on CA1 neurons. Brain Res 1014:228-235
37. Wesselingh SL, Gough NM, Finlay-Jones JJ, McDonald PJ (1990) Detection of cytokine mRNA in astrocyte cultures using the polymerase chain reaction. Lymphokine Res 9:177-185
38. Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M (1990) Collagenase-induced intracerebral hemorrhage in rats. Stroke 21:801-807
39. Clark W, Gunion-Rinker L, Lessov N, Hazel K. (1998) Citicoline treatment for experimental intracerebral hemorrhage in mice. Stroke 29:2136-2140
40. Konishi Y, Chui DH, Hirose H, Kunishita T, Tabira T (1993) Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res 609:29-35
41. Longa EZ, Weinstein PR, Carlson S, et al (1989) Reversible middle cerebral artery exclusion without craniectomy in rats. Stroke 20:84-91
42. Hasselblatt M, Jeibmann A, Riesmeier B, Maintz D, Schabitz WR (2006 ) Granulocyte-colony stimulating factor (G-CSF) and G-CSF receptor expression in human ischemic stroke. Acta Neuropathol 113(1):45-51.
43. Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, Mochizuki H, Mizuno Y, Urabe T (2005) Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 127:
44. Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Sinn DI, Lee YS, Lo EH, Kim M, Roh JK (2005) Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res 1058:120-128
45. Sheibani N, Grabowski EF, Schoenfeld DA, Whalen MJ (2004) Effect of granulocyte colony-stimulating factor on functional and histopathologic outcome after traumatic brain injury in mice. Crit Care Med 32:2274-2278
46. Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C (1992) Production of hemolymphopoietic cytokines (IL-6,IL-8,colony-stimulatingfactors) by normal human astrocytes in response to IL-1(3 and tumor necrosis factor-a. J Immunol 149:2358-2366
47. Malipiero UV. Frei K, Fontana A (1990) Production of hemopoietic colony-stimulating factors by astrocytes. J Immunol 144:3816-3821
48. Boneberg EM, Hareng L, Gantner F, Wendel A, Hartung T (2000) Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-y. Blood 95:270-276
49. Budel LM, Touw IP, Delwel R, Lowenberg B (1989) Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia. Blood 74:2668-2673
50. Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P,Mantovani A (1989) Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 337:471-473
51. Hanazono Y, Hosoi T, Kuwaki T, Matsuki S, Miyazono K, Miyagawa K, Takaku F (1990) Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils. Exp Hematol 18:1097-1103
52. Morikawa K, Morikawa S, Nakamura M, Miyawaki T (2002) Characterization of granulocyte colony-stimulating factor receptor expressed on human lymphocytes. Br J Haematol 118:296-304
53. Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y (1993) Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 91:1310-1313
54. Fukunaga R, Ishizaka-Ikeda E, Pan CX, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10:2855-2865
1．Kaptanoglu E，Solaroglu I，Okutan O，Surucu HS，Akbiyik F，Beskonakli E (2004) Erythropoietin exerts neuroprotection after acute spinal cord injury in rats：effect on lipid peroxidation and early ultrastructural findings．Neurosurg Rev 27：113-120
2．Schabitz WR，Sommer C，Zoder W．Kiessling M，Schwaninger M，Schwab S (2000) Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebralischemia．Stroke 31：2212-2221
3．Solaroglu I，Solaroglu A，Kaptanoglu E，Dede S，Haberal A，Beskonakli E，Kilinc K (2003) Erythropoietin prevents ischemia-reperfusion from inducing oxidative damage in fetal rat brain．Childs Nerv Syst 19：19-22
4．Ehrenreich H，Hasselblatt M．Dembowski C，Cepek L，Lewczuk P．Stiefel M，Rustenbeck HH，Breiter N，Jacob S，Knerlich F，Bohn M，Poser W，Ruther E，Kochen M，Gefeller O，Gleiter C，Wessel TC，De Ryck M，Itri L，Prange H，Cerami A，Brines M，Siren AL (2002) Erythropoietin therapy for acute stroke is both safe and beneficial．Mol Med 8：495-505
5．Demetri GD，Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor．Blood 78：2791-2808
6．Konishi Y，Chui DH，Hirose H，Kunishita T，Tabira T (1993) Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo．Brain Res 609：29-35
7．Gibson CL，Jones NC，Prior MJ，Bath PM．Murphy SP (2005) G-CSF suppresses edema formation and reduces interleukin-1βexpression after cerebral ischemia in mice．J Neuropathol Exp Neurol 64：763-769
8．Gibson CL，Bath PM，Murphy SP (2005) G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 25:431-439
9. Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, Mochizuki H, Mizuno Y, Urabe T (2005) Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 127:
10. Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Sinn DI, Lee YS, Lo EH, Kim M, Roh JK. (2005) Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res 1058:120-128
11. Schabitz WR, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Sholzke MN,Sommer C, Schwab S (2003) Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 34:745-751
12. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassier N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A,Kuhn HG, Schabitz WR. (2005) The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 15:2083-2098
13. Sheibani N, Grabowski EF, Schoenfeld DA, Whalen MJ (2004) Effect of granulocyte colony-stimulating factor on functional and histopathologic outcome after traumatic brain injury in mice. Crit Care Med 32:2274-2278
14. Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, Li H (2004) Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110:1847-1854
15. Six I, Gasan G, Mura E, Bordet R (2003) Beneficial effect of pharmacological mobilization of bone marrow in experimental cerebral ischemia. Eur J' Pharmacol 458:327-328
16. Wells JA, de Vos AM (1996) Hematopoieticr ecepto rcomplexes. Annu Rev Biochem 65:609-634
17. Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C (1992) Production of hemolymphopoietic cytokines (IL-6,IL-8,colony-stimulatingfactors) by normal human astrocytes in response to IL-1βand tumor necrosis factor-a. J Immunol 149:2358-2366
18. Malipiero UV, Frei K, Fontana A (1990) Production of hemopoietic colony-stimulating factors by astrocytes. J Immunol 144:3816-3821
19. Boneberg EM, Hareng L, Gantner F, Wendel A, Hartung T (2000) Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ. Blood 95:270-276
20. Budel LM, Touw IP, Delwel R, Lowenberg B (1989) Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia. Blood 74:2668-2673
21. Bussolino F, Wang JM, Defilippi P, Turrini F, Sanavio F, Edgell CJ, Aglietta M, Arese P,Mantovani A (1989) Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 337:471-473
22. Hanazono Y, Hosoi T, Kuwaki T, Matsuki S, Miyazono K, Miyagawa K, Takaku F (1990) Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils. Exp Hematol 18:1097-1103
23. Morikawa K, Morikawa S, Nakamura M, Miyawaki T (2002) Characterization ofgranulocyte colony-stimulating factor receptor expressed on human lymphocytes. Br J Haematol 118:296-304
24. Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y (1993) Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 91:1310-1313
25. Fukunaga R, Ishizaka-Ikeda E, Pan CX, Seto Y, Nagata S (1991) Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J 10:2855-2865
26. Hunter MG, Avalos BR (1998) Phosphatidylinositol 3'-kinase and SH2-containing inositol phosphatase(SHIP) are recruited by distinct positive and negative growth-regulatory domains in the granulocyte colony-stimulating factor receptor. J Immunol 160:4979-4987
27. Shimoda K, Feng J, Murakami H, Nagata S, Watling D, Rogers NC, Stark GR, Kerr IM, Ihle JN (1997) Jakl plays an essential role for receptor phosphorylation and Stat activation in response to granulocyte colony-stimulating factor. Blood 90:597-604
28. Tian SS, Lamb P, Seidel HM, Stein RB, Rosen J (1994) Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood 84:1760-1764
29. Ward AC, Loeb DM, Soede-Bobok AA, Touw IP, Friedman AD (2000) Regulation of granulopoiesis by transcription factors and cytokine signals. Leukemia 14:973-990
30. Dong F, Lamer AC (2000) Activation of Akt kinase by granulocyte colony-stimulating factor(G-CSF):evidence for the role of a tyrosine kinase activity distinct from the Janus kinases. Blood 95:1656-1662
31. Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J, Storb R,Buckner CD (1995) Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 85:1655-1658
32. Carlsson G, Ahlin A, Dahllof G, Elinder G Henter JI, Palmblad JI (2004) Efficacy and safety of two different rG-CSF preparations in the treatment of patients with severe congenital neutropenia. Br J Haematol 126:127-132
33. Kocherlakota P, La Gamma EF (1997) Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia.Pediatrics 100:E6
34. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G (1996) Filgrastim(r-metHuG-CSF): the first 10 years. Blood 88:1907-1929
35. Kleinschnitz C, Schroeter M, Jander S, Stoll G (2004) Induction of granulocyte colony-stimulating factor mRNA by focal cerebral ischemia and cortical spreading depression. Brain Res Mol Brain Res 131:73-78
36. Barone FC, Feuerstein GZ (1999) Inflammatory mediators and stroke:new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19:819-834
37. Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391-397
38. Whalen MJ, Carlos TM, Wisniewski SR, Clark RS, Mellick JA, Marion DW,Kochanek PM (2000) Effect of neutropenia and granulocyte colony stimulating factor-induced neutrophilia on blood-brain barrier permeability and brain edema after traumatic brain injury in rats. Crit Care Med 28:3710-3717
39. Quagliarello VJ, Wispelwey B, Long WJ Jr, Scheld WM (1991) Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in therat.Characterization and comparison with tumor necrosis factor. J Clin Invest 87:1360-1366
40. Rosenman SJ, Shrikant P, Dubb L, Benveniste EN, Ransohoff RM (1995) Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. J Immunol 154:1888-1899
41. Zavala F, Abad S, Ezine S, Taupin V, Masson A, Bach JF (2002) G-CSF therapy o fongoing experimental allergic encephalomyelitis via chemokine-and cytokine-based immune deviation. J Immunol 168:2011-2019
42. Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, Frisch S,Reed JC (1998) Regulation of cell death protease caspase-9 by phosphorylation.Science 282:1318-1321
43. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G (1997) Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278:687-689
44. Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275:661-665
45. Fujio Y, Guo K, Mano T, Mitsuuchi Y, Testa JR., Walsh K (1999) Cell cycle withdrawal promotes myogenic induction of Akt,a positive modulator of myocytesurvival. Mol Cell Biol 19:5073-5082
46. Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE (2000) Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 275:10761-10766
47. Kim S, Jee K, Kim D, Koh H, Chung J (2001) Cyclic AMP inhibits Akt activity by blocking the membrane localization of PDK1. J Biol Chem 276:12864-12870
48. Liu L, Cavanaugh JE, Wang Y, Sakagami H, Mao Z, Xia Z (2003) ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons Proc Natl Acad Sci USA 100:8532-8537
49. Watson FL, Heerssen HM, Bhattacharyya A, Klesse L, Lin MZ, Segal RA (2001)Neurotrophins use the Erk5 pathway to mediate a retrograde survival response. Nat Neurosci 4:981-988
50. Tehranchi R, Fadeel B, Forsblom AM, Christensson B, Samuelsson J, Zhivotovsky B,Hellstrom-Lindberg E (2003) Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Blood 101:1080-1086
51. Wang L, Gang ZZ, Lan ZR, Chopp M (2005) Activation of the PI3-K/Ak pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricularzone. J Cereb Blood Flow Metab 2005:1150-1158
52. Katakowski M, Zhang ZG, Chen J, Zhang R, Wang Y, Jiang H, Zhang L, Robin A, Li Y,Chopp M (2003) Phosphoinositide 3-kinase promotes adult subventricular neuroblast migration after stroke. J Neurosci Res 74:494-501
53. Levesque JP, Hendy J, Takamatsu Y Simmons PJ, Bendall LJ (2003) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest 111:187-196
54. Peng H, Huang Y, Rose J, Erichsen D, Herek S, Fujii N, Tamamura H, Zheng J (2004) Stromal cell-derived factor1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells. J Neurosci Res 76:35-50
55. Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J,Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factorla/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101:18117-18122
56. Robin AM, Zhang ZG, Wang L, Zhang RL, Katakowski M, Zhang L, Wang Y, Zhang C,Chopp M (2006) Stromal cell-derived factor 1 mediates neural progenitor cell motility after focal cerebral ischemia. J Cereb Blood Flow Metab 26:125-134
57. Grigg AP, Roberts AW, Raunow H, Houghton S, Layton JE, Boyd AW, McGrath KM, Maher D (1995) Optimizing dose and scheduling of filgrastim(granulocyte colony-stimulating factor)for mobilization and collection of peripheral blood progenitor cells in normal volunteers. Blood 86:4437-4445
58. Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Hollt V, Schulz S (2002) A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain:Isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci 22:5865-5878
59. Khan M, Sekhon B, Giri S, Jatana M, Gilg AG, Ayasolla K, Elango C, Singh AK, Singh Ⅰ (2005) S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. J Cereb Blood Flow Metab 25:177-192
60. Lee H, Kim YO, Kim H, Kim SY, Noh HS, Kang SS, Cho GJ, Choi WS, SukK (2003) Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microslia. FASEB J 17:1943-1944
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |