
高压氧治疗促进HIBD新生大鼠内源性神经干细胞的迁移与分化
王晓莉, 杨于嘉, 谢岷, 王庆红, 余小河
中国当代儿科杂志 ›› 2009, Vol. 11 ›› Issue (9) : 749-752.
高压氧治疗促进HIBD新生大鼠内源性神经干细胞的迁移与分化
Hyperbaric oxygen promotes the migration and differentiation of endogenous neural stem cells in neonatal rats with hypoxic ischemic brain damage
目的:该研究探讨了高压氧(HBO)对缺氧缺血性脑损伤(HIBD) 新生大鼠内源性神经干细胞(NSCs)的迁移与分化的影响。方法:7 日龄 Sprague-Dawley 新生大鼠随机分为对照组,模型组及HBO组。采用 Rice-Vannucci 方法制成 HIBD 模型。造模后 3 h 内行HBO 治疗。分别于 HBO治疗后 7 d、14 d、 28 d,采用 BrdU/DCX,BrdU/β-tubulin,BrdU/GFAP和BrdU/O4免疫荧光双标法,用共聚焦显微镜动态检测侧脑室室管膜下区(subventricular zone, SVZ)与大脑皮层内源性 NSCs的迁移与分化。结果:治疗后7 d,HBO 组损伤侧SVZ 区 BrdU+DCX+细胞数(84±21 个/mm2)增加,多于对照组(39±14 个/mm2)与模型组(68±17 个/mm2)(P<0.05);治疗后14 d,SVZ区BrdU+DCX+ 细胞数减少,而皮层区BrdU+DCX+ 细胞数增加,HBO组明显多于对照组(P<0.01);治疗后28 d,各组大脑皮层BrdU+DCX+ 细胞数减少,大脑皮层出现BrdU+β-tubulin+,BrdU+GFAP+,BrdU+O4+细胞。HBO组BrdU+β-tubulin+与BrdU+O4+细胞数显著高于对照组与模型组(P<0.05)。结论:高压氧可促进 HIBD 新生大鼠内源性NSCs迁移到大脑皮层并分化为成熟的神经细胞。[中国当代儿科杂志,2009,11(9):749-752]
OBJECTIVE: To explore the effects of hyperbaric oxygen (HBO) treatment on the migration and differentiation of endogenous neural stem cells (NSCs) in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: Seven-day-old Sprague-Dawley rats were randomly divided into the normal control (CON), the HIBD model and the HBO groups (HBO treatment was administered at 2 ATA, once daily for 7 days within 3 hrs after HIBD). HIBD model was prepared according to the classic Rice-Vannucci method. BrdU/DCX, BrdU/β-tubulin, BrdU/GFAP and BrdU/O4 immunofluorescence were examined by confocal microscopy in the subventricular zone (SVZ) and the cortex 7, 14 and 28 days after HBO treatment. RESULTS: The BrdU+DCX+ cells in the SVZ (84±21 cells/mm2) in the HBO group were significantly higher than those in the CON group (39±14 cells/mm2) (P<0.05) and the HIBD model group (68±17 cells/mm2) (P<0.05) 7 days after HBO treatment. Fourteen days after HBO treatment, the BrdU+ DCX+ cells decreased in the SVZ and more cells were observed in the cortex in the HBO group as compared with the CON group (P<0.01). The BrdU+ β-tubulin+, BrdU+GFAP+ and BrdU+ O4+ cells were observed in the cortex, and more BrdU+β-tubulin+ and BrdU+ O4+ cells were observed in the HBO group as compared with the CON and the HIBD model groups (P<0.05) 28 days after HBO treatment. CONCLUSIONS: HBO treatment may promote endogenous NSCs to migrate to the cortex and differentiate into mature neurocytes in neonatal rats with HIBD.[Chin J Contemp Pediatr, 2009, 11 (9):749-752]
Hypoxic-ischemic brain damage / Hyperbaric oxygen / Neural stem cell / Neonatal rats
[1]Verklan MT. The chilling details:hypoxic-ischemic encephalopathy[J]. J Perinat Neonatal Nurs, 2009, 23(1):59-68.
[2]余小河, 杨于嘉, 王霞, 王庆红, 谢岷, 祁伯祥, 等. 高压氧对缺氧缺血性脑损伤新生大鼠内源性神经干细胞和髓鞘的保护作用[J]. 中国当代儿科杂志, 2006, 8(1):33-37.
[3]王晓莉, 杨于嘉, 王庆红, 谢岷, 余小河, 刘沉涛, 等. 高压氧促HIBD新生大鼠内源性神经干细胞增殖过程中Wnt-3蛋白的变化[J]. 中国当代儿科杂志, 2007, 9(3):241-246.
[4]Rice JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat[J]. Ann Neurol, 1981, 9(4):131-141.
[5]Sugiura S, Kitagawa K, Tanaka S, Todo K, Omura-Matsuoka E, Sasaki T, et al. Adenovirus-mediated gene transfer of heparin-binding epidermal growth factor-like growth factor enhances neurogenesis and angiogenesis after focal cerebral ischemia in rats[J]. Stroke, 2005, 36(4):859-864.
[6]Yang Z, Levison SW. Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone[J]. Neuroscience, 2006, 139(2):555-564.
[7]Ma YP, Ma MM, Cheng SM, Ma HH, Yi XM, Xu GL, et al. Intranasal bFGF-induced progenitor cell proliferation and neuroprotection after transient focal cerebral ischemia[J]. Neurosci Lett, 2008, 437(2):93-97.
[8]Ma M, Ma Y, Yi X, Guo R, Zhu W, Fan X, et al. Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone[J]. BMC Neurosci, 2008, 9:117.
[9]Lee JH, Shin HK, Park SY, Kim CD, Lee WS, Hong KW. Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats[J]. Exp Neurol, 2009, 215(1):87-94.
[10]Peng J, Xie L, Jin K, Greenberg DA, Andersen JK. Fibroblast growth factor 2 enhances striatal and nigral neurogenesis in the acute 1-methyl4-phenyl-1,2,3,6-tetra-hydropyridine model of Parkinson's disease[J]. Neuroscience, 2008, 153(3):664-670.
[11]lmitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, 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[J]. Proc Natl Acad Sci, 2004, 101(52):18117-18122.
[12]Hayashi T, Iwai M, Ikeda T, Jin G, Deguchi K, Nagotani S, et al. Neural precursor cells division and migration in neonatal rat brain after ischemic/hypoxic injury[J]. Brain Res, 2005, 1038(1):41-49.
[13]Ye M, Wang XJ, Zhang YH, Lu GQ, Liang L, Xu JY, et al. Therapeutic effects of differentiated bone marrow stromal cell transplantation on rat models of Parkinson's disease[J]. Parkinsonism Relat Disord, 2007, 13(1):44-49.