Petzold A, Stiefel D, Copp A J
Department of Neuroimmunology, Institute of Neurology, Queen Square, London, UK.
J Neurochem. 2005 Oct;95(2):594-8. doi: 10.1111/j.1471-4159.2005.03432.x.
Myelomeningocele (MMC), the most severe form of spina bifida (SB), causes neurological deficit. Injury to the spinal cord is thought to begin in utero. We investigated whether brain-specific proteins (BSPs) would enable us to monitor the development of MMC-related tissue damage during pregnancy in an animal model with naturally occurring SB (curly tail/loop tail mouse; n = 256). Amniotic fluid levels of neurofilament heavy chain (NfH), glial acidic fibrillary protein (GFAP) and S100B were measured by standard ELISA techniques. The amniotic fluid levels of all BSPs were similar in SB and control mice on embryonic day (E) 12.5 and 14.5, whereas a significant increase was observed for GFAP in SB mice on E16.5. Levels of all BSPs were significantly increased in SB mice on E18.5. The rapid increase in GFAP, paralleled by a moderate increase in NfH and S100B, suggests that spinal cord damage starts to accelerate around E16.5. The macroscopic size of the MMC was related to NfH level on E16.5 and E18.5, suggesting that axonal degeneration is most severe in large MMC. Amniotic fluid BSP measurements may provide important information for balancing the risks and benefits to mother and child of in utero surgery for MMC.
脊髓脊膜膨出（MMC）是脊柱裂（SB）最严重的形式，会导致神经功能缺损。脊髓损伤被认为始于子宫内。我们研究了脑特异性蛋白（BSPs）是否能使我们在患有自然发生的SB的动物模型（卷尾/环尾小鼠；n = 256）中监测孕期MMC相关组织损伤的发展情况。通过标准酶联免疫吸附测定技术测量羊水神经丝重链（NfH）、胶质纤维酸性蛋白（GFAP）和S100B的水平。在胚胎第（E）12.5天和14.5天，SB小鼠和对照小鼠羊水内所有BSPs的水平相似，而在E16.5天观察到SB小鼠的GFAP显著增加。在E18.5天，SB小鼠所有BSPs的水平均显著增加。GFAP的快速增加，同时伴有NfH和S100B的适度增加，表明脊髓损伤在E16.5天左右开始加速。MMC的宏观大小与E16.5天和E18.5天的NfH水平相关，表明大的MMC中轴突退变最为严重。羊水BSP测量可能为平衡MMC宫内手术对母婴的风险和益处提供重要信息。
