The Effect of Recombinant Stromal Cell-Derived Factor-1 Treatment on Hypoxic-Ischemic Brain Injury in Neonatal Mice

WeiWei Zhu; XiaoLi Ma; Feng Li; Jun Wang; LiChun Yu; Mi Xu; AiHua Ma; AiLi Guo; Nan Zhang

doi:10.1055/s-0032-1325121

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2012; 43(06): 320-331
DOI: 10.1055/s-0032-1325121

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Effect of Recombinant Stromal Cell-Derived Factor-1 Treatment on Hypoxic-Ischemic Brain Injury in Neonatal Mice

WeiWei Zhu

¹Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China

,

XiaoLi Ma

²Central Laboratory, Jinan Central Hospital affiliated to Shandong University, Jinan, China

,

Feng Li

¹Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China

,

Jun Wang

¹Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China

,

LiChun Yu

³Department of Pediatrics, Provincial Hospital affiliated to Shandong University, Jinan, China

,

Mi Xu

¹Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China

,

AiHua Ma

³Department of Pediatrics, Provincial Hospital affiliated to Shandong University, Jinan, China

,

AiLi Guo

¹Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China

,

Nan Zhang

¹Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China

› Institutsangaben

Abstract

Background Stromal cell-derived factor-1 (SDF-1) plays a critical role in adult brain injury repair including neurogenesis and vasculogenesis. However, the effects of recombinant SDF-1(rSDF-1) treatment on hypoxic-ischemic (HI) brain injury in neonatal mice are not clear.

Materials and Methods Seven-day-old (P7) C57BL/6J mice were divided into sham group, control group, and rSDF-1 group. Mice brains were collected to determine histopathological damage and the expression level of SDF-1, caspase-3, and Ki67 on P8, P10, P14, and P21. Passive avoidance and elevated plus-maze tests were also assessed on P20 and P21.

Results Compared with control group, rSDF-1 treatment increased the weight ratio of left and right brain hemisphere (p < 0.05), reduced the number of electric foot shocks (p < 0.05) and the percentage of time spent in the open arms (p < 0.05), meanwhile, increased the retention latency (p < 0.05) and the percentage of time spent in the enclosed arms (p < 0.05) on P20 and P21. High expression of Ki67 and low expression of caspase-3 were also observed.

Discussion This study showed that rSDF-1 treatment effectively alleviated brain injury shown by reducing in caspase-3 expression and increasing in Ki67 expression. Moreover, rSDF-1 treatment significantly improved behavioral performances in juvenile mice after HI.

Keywords

hypoxia-ischemia brain injury - stromal cell-derived factor-1 - apoptosis - proliferation - functional recovery - neonatal mice

Volltext

Referenzen

References
1 Graham EM, Ruis KA, Hartman AL, Northington FJ, Fox HE. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008; 199 (6) 587-595
2 Vannucci RC. Hypoxic-ischemic encephalopathy. Am J Perinatol 2000; 17 (3) 113-120
3 Imitola J, Raddassi K, Park KI , et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A 2004; 101 (52) 18117-18122
4 Lazarini F, Tham TN, Casanova P, Arenzana-Seisdedos F, Dubois-Dalcq M. Role of the α-chemokine stromal cell-derived factor (SDF-1) in the developing and mature central nervous system. Glia 2003; 42 (2) 139-148
5 Li M, Ransohoff RM. Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol 2008; 84 (2) 116-131
6 Peng H, Huang Y, Rose J , et al. Stromal cell-derived factor 1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells. J Neurosci Res 2004; 76 (1) 35-50
7 Lu M, Grove EA, Miller RJ. Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A 2002; 99 (10) 7090-7095
8 Tissir F, Wang CE, Goffinet AM. Expression of the chemokine receptor Cxcr4 mRNA during mouse brain development. Brain Res Dev Brain Res 2004; 149 (1) 63-71
9 Tran PB, Ren D, Veldhouse TJ, Miller RJ. Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells. J Neurosci Res 2004; 76 (1) 20-34
10 Ceradini DJ, Kulkarni AR, Callaghan MJ , et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 2004; 10 (8) 858-864
11 Shyu WC, Lin SZ, Yen PS , et al. Stromal cell-derived factor-1 α promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats. J Pharmacol Exp Ther 2008; 324 (2) 834-849
12 Wang Y, Deng YB, Zhou GQ. SDF-1α/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res 2008; 1195: 104-112
13 Hiasa K, Ishibashi M, Ohtani K , et al. Gene transfer of stromal cell-derived factor-1alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation 2004; 109 (20) 2454-2461
14 Yamaguchi J, Kusano KF, Masuo O , et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107 (9) 1322-1328
15 Ji JF, He BP, Dheen ST, Tay SS. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells 2004; 22 (3) 415-427
16 Ni HT, Hu S, Sheng WS , et al. High-level expression of functional chemokine receptor CXCR4 on human neural precursor cells. Brain Res Dev Brain Res 2004; 152 (2) 159-169
17 Peng Y, Jiang BH, Yang PH , et al. Phosphatidylinositol 3-kinase signaling is involved in neurogenesis during Xenopus embryonic development. J Biol Chem 2004; 279 (27) 28509-28514
18 Miller JT, Bartley JH, Wimborne HJ , et al. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury. BMC Neurosci 2005; 6: 63
19 Taniguchi H, Mohri I, Okabe-Arahori H , et al. Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury. J Neurosci 2007; 27 (16) 4303-4312
20 Kerfoot SM, Andonegui G, Bonder CS, Liu L. Exogenous stromal cell-derived factor-1 induces modest leukocyte recruitment in vivo. Am J Physiol Heart Circ Physiol 2008; 294 (6) H2524-H2534
21 Rice III JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 1981; 9 (2) 131-141
22 Yuan JS, Reed A, Chen F, Stewart Jr CN. Statistical analysis of real-time PCR data. BMC Bioinformatics 2006; 7: 85
23 Jing H, Ai-Rong Q, Li-Fang H , et al. Semi-quantitative analysis methods of tubulin based on the fluorescent images. J Fourth Mil Med Univ. 2009; 30 (24)
24 Fan LW, Lin S, Pang Y , et al. Hypoxia-ischemia induced neurological dysfunction and brain injury in the neonatal rat. Behav Brain Res 2005; 165 (1) 80-90
25 Sasaki K, Fan LW, Tien LT, Ma T, Loh HH, Ho IK. The interaction of morphine and gamma-aminobutyric acid (GABA)ergic systems in anxiolytic behavior: using mu-opioid receptor knockout mice. Brain Res Bull 2002; 57 (5) 689-694
26 Corti S, Locatelli F, Papadimitriou D , et al. Multipotentiality, homing properties, and pyramidal neurogenesis of CNS-derived LeX(ssea-1) +/CXCR4+ stem cells. FASEB J 2005; 19 (13) 1860-1862
27 Shichinohe H, Kuroda S, Yano S, Hida K, Iwasaki Y. Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct. Brain Res 2007; 1183: 138-147
28 Calvert JW, Yin W, Patel M , et al. Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a neonatal rat model. Brain Res 2002; 951 (1) 1-8
29 Hermans RH, Hunter DE, McGivern RF, Cain CD, Longo LD. Behavioral sequelae in young rats of acute intermittent antenatal hypoxia. Neurotoxicol Teratol 1992; 14 (2) 119-129
30 Agmo A, Belzung C. The role of subtypes of the opioid receptor in the anxiolytic action of chlordiazepoxide. Neuropharmacology 1998; 37 (2) 223-232
31 Schmitt U, Lüddens H, Hiemke C. Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats. J Neural Transm 2002; 109 (5-6) 871-880
32 Mirshahi F, Pourtau J, Li H , et al. SDF-1 activity on microvascular endothelial cells: consequences on angiogenesis in in vitro and in vivo models. Thromb Res 2000; 99 (6) 587-594
33 Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997; 185 (1) 111-120
34 Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 1996; 184 (3) 1101-1109
35 Hill WD, Hess DC, Martin-Studdard A , et al. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol 2004; 63 (1) 84-96
36 Kokovay E, Goderie S, Wang Y , et al. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell 2010; 7 (2) 163-173
37 Tabatabai G, Bähr O, Möhle R , et al. Lessons from the bone marrow: how malignant glioma cells attract adult haematopoietic progenitor cells. Brain 2005; 128 (Pt 9) 2200-2211
38 Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res 2010; 16 (11) 2927-2931
39 Guo Y, Hangoc G, Bian H, Pelus LM, Broxmeyer HE. SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells. Stem Cells 2005; 23 (9) 1324-1332
40 West T, Atzeva M, Holtzman DM. Caspase-3 deficiency during development increases vulnerability to hypoxic-ischemic injury through caspase-3-independent pathways. Neurobiol Dis 2006; 22 (3) 523-537
41 Fukunaga K, Kawano T. Akt is a molecular target for signal transduction therapy in brain ischemic insult. J Pharmacol Sci 2003; 92 (4) 317-327
42 Tomimatsu T, Fukuda H, Endo M , et al. Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat: phosphorylation of Akt, activation of caspase-3-like protease. Neurosci Lett 2001; 312 (1) 21-24
43 do Carmo A, Patricio I, Cruz MT, Carvalheiro H, Oliveira CR, Lopes MC. CXCL12/CXCR4 promotes motility and proliferation of glioma cells. Cancer Biol Ther 2010; 9 (1) 56-65
44 Yang Z, Levison SW. Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone. Neuroscience 2006; 139 (2) 555-564
45 Plane JM, Liu R, Wang TW, Silverstein FS, Parent JM. Neonatal hypoxic-ischemic injury increases forebrain subventricular zone neurogenesis in the mouse. Neurobiol Dis 2004; 16 (3) 585-595
46 Bonavia R, Bajetto A, Barbero S, Pirani P, Florio T, Schettini G. Chemokines and their receptors in the CNS: expression of CXCL12/SDF-1 and CXCR4 and their role in astrocyte proliferation. Toxicol Lett 2003; 139 (2-3) 181-189
47 Yang Z, Levison SW. Perinatal hypoxic/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors. Dev Neurosci 2007; 29 (4-5) 331-340
48 Felling RJ, Snyder MJ, Romanko MJ , et al. Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. J Neurosci 2006; 26 (16) 4359-4369
49 Miles DK, Kernie SG. Hypoxic-ischemic brain injury activates early hippocampal stem/progenitor cells to replace vulnerable neuroblasts. Hippocampus 2008; 18 (8) 793-806
50 Sung SM, Jung DS, Kwon CH, Park JY, Kang SK, Kim YK. Hypoxia/reoxygenation stimulates proliferation through PKC-dependent activation of ERK and Akt in mouse neural progenitor cells. Neurochem Res 2007; 32 (11) 1932-1939
51 Otaegi G, Yusta-Boyo MJ, Vergaño-Vera E , et al. Modulation of the PI 3-kinase-Akt signalling pathway by IGF-I and PTEN regulates the differentiation of neural stem/precursor cells. J Cell Sci 2006; 119 (Pt 13) 2739-2748
52 Yano T, Liu Z, Donovan J, Thomas MK, Habener JF. Stromal cell derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt. Diabetes 2007; 56 (12) 2946-2957