Nishigori Hidekazu, Mazzuca Delfina M, Nygard Karen L, Han Victor K, Richardson Bryan S
Department of Obstetrics and Gynaecology, The Children's Health Research Institute, The University of Western Ontario, London, Canada.
Reprod Sci. 2008 Nov;15(9):895-905. doi: 10.1177/1933719108324135.
We have determined the developmental change in immunoreactivity for brain-derived neurotrophic factor and its high-affinity tyrosine kinase receptor, TrkB, in the ovine fetal brain with advancing gestation and in response to intermittent umbilical cord occlusion, which might then contribute to adverse neurodevelopment. Fetal sheep (control and experimental groups at 0.75 and 0.90 of gestation) were studied over 4 days with umbilical cord occlusions performed in the experimental group animals by complete inflation of an occluder cuff for 90 seconds every 30 minutes for 3 to 5 hours each day. Animals were then euthanized and the fetal brains perfusion fixed and prepared for subsequent histology with the distribution of brain-derived neurotrophic factor and tyrosine kinase receptor immunoreactivity determined by immunohistochemistry. In the control group animals brain-derived neurotrophic factor immunoreactivity decreased in the gray matter, thalamus, and hippocampus but increased in the white matter, while tyrosine kinase receptor immunoreactivity decreased in all regions (most P < .01), with advancing gestation consistent with the developmental change from neurogenesis/gliagenesis to myelination over this time period. Intermittent umbilical cord occlusion as studied with severe but limited hypoxemia resulted in a variable decrease in brain-derived neurotrophic factor and tyrosine kinase receptor immunoreactivity for all brain regions in the preterm animals (most P < .01) when protein turnover is higher, but a selective increase in brain-derived neurotrophic factor immunoreactivity in the hippocampus of the near-term animals consistent with a heightened vulnerability for necrotic/apoptotic injury at this time. As such, brain-derived neurotrophic factor-tyrosine kinase receptor in the ovine fetal brain may be altered with intermittent hypoxic insults over the latter part of pregnancy with potential for longer term neurologic consequences.
我们已经确定了绵羊胎儿大脑中脑源性神经营养因子（BDNF）及其高亲和力酪氨酸激酶受体TrkB的免疫反应性随妊娠进展以及对间歇性脐带闭塞（这可能导致不良神经发育）的发育变化。对胎羊（妊娠0.75和0.90时的对照组和实验组）进行了为期4天的研究，实验组动物通过每隔30分钟将阻塞袖带完全充气90秒，每天进行3至5小时的脐带闭塞。然后对动物实施安乐死，对胎儿大脑进行灌注固定，并准备进行后续组织学检查，通过免疫组织化学确定脑源性神经营养因子和酪氨酸激酶受体免疫反应性的分布。在对照组动物中，随着妊娠进展，脑源性神经营养因子在灰质、丘脑和海马中的免疫反应性降低，但在白质中增加，而酪氨酸激酶受体免疫反应性在所有区域均降低（大多数P<0.01），这与该时间段内从神经发生/胶质发生到髓鞘形成的发育变化一致。在蛋白质周转率较高的早产动物中，如通过严重但有限的低氧血症研究的间歇性脐带闭塞导致所有脑区的脑源性神经营养因子和酪氨酸激酶受体免疫反应性出现不同程度的降低（大多数P<0.01），但在足月动物的海马中脑源性神经营养因子免疫反应性选择性增加，这与此时坏死/凋亡性损伤的易感性增加一致。因此，绵羊胎儿大脑中的脑源性神经营养因子-酪氨酸激酶受体可能会因妊娠后期的间歇性缺氧损伤而改变，具有产生长期神经后果的可能性。
