洪新如，曲伸，侍坚，陈新民.脑内移植BDNF载体细胞对新生大鼠缺氧缺血性脑损伤后运动机能和行为的影响[J].中华物理医学与康复杂志,2002,(1):.-
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| 脑内移植BDNF载体细胞对新生大鼠缺氧缺血性脑损伤后运动机能和行为的影响 |
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| DOI： |
| 中文关键词: 脑源性神经营养因子 脑缺氧 脑缺血 新生大鼠 |
| 英文关键词: Brain derived neurotrophic factor Cerebral anoxia Cerebral ischemia Neonatal rat |
| 基金项目:全军“九·五”医学科研规划科研基金资助项目(基金编号：98D022) |
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| 中文摘要: |
| 目的探讨脑内移植脑源性神经营养因子(BDNF)载体细胞对新生大鼠缺氧缺血性脑损伤后存活、运动机能和行为的影响。方法7 d龄新生大鼠一侧颈总动脉结扎联合低氧吸入法制成缺氧缺血性脑损伤模型。在损伤后即刻，于单侧皮层内植入构建的可稳定表达和分泌BDNF的大鼠成肌细胞，观察植入4周后大鼠存活、运动机能和行为的变化。结果BDNF载体细胞可稳定表达BDNF mRNA，其分泌上清液可维持PC12细胞存活、促进突触生长，脑内移植后42d，移植组动物死亡率显著降低(28.6%，对照值为57.7%)；倾斜临界角度虽仍低于假伤组，但显著高于移植不含BDNF载体细胞的对照组；开场行为的水平、垂直运动值均显著高于对照组，多数时间点上显著低于假伤组。结论脑内移植可稳定表达和分泌活性BDNF的载体细胞可显著降低新生大鼠缺氧缺血性脑损伤后的死亡率，对运动机能和行为的恢复有良好的促进作用。 |
| 英文摘要: |
| Objective To investigate the effects of intracortical transplantation of genetically modified myoblasts producing brain derived neurotrophic factor on locomotion and neurobehavior in neonatal rats subjected to hypoxic ischemic encephalopathy (HIE).MethodsFifty eight 7 day old pups were randomized into shamoperated group (C, 11 pups), HIE Plus BDNF transplantation group (B, 21 pups) and HIE Plus mock transplantation group (A, 26 pups). A rat myoblast cell line expressing BDNF (BDNF(+)/L- 6TG) was constructed with the identification of BDNF mRNA expression and BDNF bioactivity by Northern blotting and bioassay with PC12 cells. A unilateral stereoaxical tranplantation of either BDNF (+)/L- 6TG(B) or BDNF( ) /L- 6TG(absence of BDNF, A) at 0.8 μl of cell suspension (4×104/μl ) into the left cortex of the brain was carried out shortly after HIE undergone by ligation of left common carotid artery in animals in group B or A, followed by a 2.5 h inhalation of humidified 8% O2 Plus 92% N2 at 37℃. Locomotive and neurobehavioral changes were observed during 29～ 42 d after the graft using both declinational critical angle test and open field test. The group C served as basal control.ResultsThat the genetically modified myoblasts expressed and released BDNF in vitro was confirmed by Northern blotting and culture supernatant promoting the survival of PC12 cells and outgrowth of their dendrites. Mortality of the injured pups in 42 d after HIE was significantly reduced in group B (6/21) vs group A (15/26) (P<0.05). Declinational critical angles were markedly increased in group B compared to group A at all the time points observed, although they were still smaller than those in group C. Similar change patterns were seen in open field test. ConclusionThe present data suggest that genetically modified myoblasts expressing and secreting bioactive BDNF in vitro exert a protective function of reducing locomotive and neurbehavioral abnormalities as well as the mortality rate of HIE rats after being transplanted into HIE brain. |
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