Effects of intrauterine inflammation on developing rat brain
Effects of intrauterine inflammation on developing rat brain
复制标题
DOI：
10.1002/jnr.10423
复制
发表时间：
2002-11-15
影响因子：
4.2
通讯作者：
Hallenbeck, JM
中科院分区：
文献类型：
--
作者：
Bell, MJ;Hallenbeck, JM
发育过程中大脑白质受损可导致脑瘫 (CP)，这是一组异质性临床综合征，可导致终生运动和姿势障碍。脑室周围白质软化 (PVL) 是白质内的一种病理过程，其特征是少突胶质细胞丢失，与 CP 的发生有关。临床上，CP和PVL与宫内感染和炎症有关，但所涉及的机制尚不清楚。我们在 Lewis 和 Fischer 344 只大鼠中建立了宫内炎症模型，以研究宫内炎症对神经胶质细胞发育的影响。在妊娠15天（E15）时，对怀孕的大鼠进行宫颈内注射脂多糖（LPS），并确定引起低胎儿死亡率的LPS剂量。在 E20 时，接受治疗的胎儿大脑内 TUNEL+ 细胞核和肿瘤坏死因子 (TNF)-α 免疫反应区域有所增加。在允许存活至出生后第 21 天 (PND 21) 的第二组动物中，针对几种神经胶质标记物进行了免疫染色。与胼胝体内的假手术组相比，治疗组幼犬中少突胶质细胞特异性蛋白 2', 3'-环核苷酸磷酸二酯酶 (CNP) 和髓磷脂蛋白脂蛋白 (PLP) 的染色有所减少，胼胝体是一种白质结构，用作白质发育的代表区域。通过神经胶质原纤维酸性蛋白（GFAP）染色观察到，接受治疗的幼崽脑血管内壁的星形胶质细胞被激活，而假手术幼崽则没有。使用 OX42 作为细胞标记物未检测到活化的小胶质细胞。我们的宫内炎症模型导致损伤后早期 TUNEL 和 TNF-α 染色增加，表明凋亡细胞死亡增加，可能是通过细胞因子相关机制实现的。 (C) 2002 Wiley-Liss, Inc.
Damage to the white matter in the brain during development can lead to cerebral palsy (CP), a heterogeneous group of clinical syndromes that results in life-long disorders of movement and posture. Periventricular leukomalacia (PVL) is a pathological process within the white matter characterized by oligodendrocyte loss and is associated with the development of CP. Clinically, CP and PVL are associated with intrauterine infection and inflammation, but mechanisms involved are not well understood. We developed a model of intrauterine inflammation in Lewis and Fischer 344 rats to study the effects of intrauterine inflammation on developing glia. Pregnant rats were intracervically injected with lipopolysaccharide (LPS) at 15 days of gestation (E15) and a dose of LPS that caused low fetal mortality was determined. At E20, treated fetuses had increased TUNEL+ nuclei and tumor necrosis factor (TNF)-alpha-immunoreactive areas within the brains. In a second series of animals allowed to survive until postnatal day 21 (PND 21), immunostaining was performed against several glial markers. Staining for the oligodendrocyte-specific proteins 2', 3'-cyclic nucleotide phosphodiesterase (CNP) and myelin proteolipid protein (PLP) was decreased in treated pups compared to shams within the corpus callosum, a white matter structure used as a representative area of developing white matter. Treated pups had activated astrocytes lining cerebral blood vessels, as observed by glial fibrillary acidic protein (GFAP) staining, while sham pups did not. Activated microglia were not detected using OX42 as a cell marker. Our model of intrauterine inflammation causes increased TUNEL and TNF-alpha staining early after injury, suggesting increased apoptotic cell death, possibly by cytokine-related mechanisms. (C) 2002 Wiley-Liss, Inc.