No phenotype associated with established lipopolysaccharide model for cerebral palsy
No phenotype associated with established lipopolysaccharide model for cerebral palsy
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DOI：
10.1016/j.ajog.2004.12.053
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发表时间：
2005-03-01
影响因子：
9.8
通讯作者：
Spong, CY
中科院分区：
文献类型：
--
作者：
Poggi, SH;Park, J;Spong, CY
目的：脑性瘫痪（CP）与儿童痉挛、癫痫发作和瘫痪有关。在发育中的大脑中，少突胶质细胞损伤导致脑室周围白质软化（PVL）。CP的动物模型使用产前缺氧和PVL的组织病理学感染作为终点。为了评估这一组织学终点是否与CP表型相关，我们复制了PVL的脂多糖（LPS）模型，I并评估了发育、行为和运动outcomes.Study design：在妊娠第15天，Fischer 344大鼠宫颈内注射0.1 mg/kg LPS（n = 5）或盐水（n = 4）。分娩后，在第1天至第21天进行发育里程碑评价（LPS = 45;对照= 30只幼仔）。男性也在2.5个月时进行了测试，使用开放领域，旋转棒，和焦虑测试。在第21天，灌注2只幼仔/窝进行免疫组织化学，并用2种少突胶质细胞抗体染色：2 '，d'-环核苷酸磷酸二酯酶（CNP）和髓鞘蛋白脂质蛋白（PLP），使用NIH Image软件评估染色的相对密度。统计分析包括Mann-Whitney U和方差分析（ANOVA）。结果：LPS幼仔表现出降低的CNP（P =.04）和PLP（P =.06）染色，复制了模型。在新生儿体重、翻正、负趋地性、悬崖厌恶、生根、前肢抓握、听觉惊吓、空中翻正、睁眼和活动方面没有观察到差异。令人惊讶的是，LPS暴露的新生大鼠掌握了前肢的放置（P
Objective: Cerebral palsy (CP) is associated with childhood spasticity, seizures, and paralysis. Oligodendrocyte damage resulting in periventicular leukomalacia (PVL) in the developing brain has been implicated. Animal models of CP have used prenatal hypoxia and infection with histopathology of PVL as the end point. To evaluate whether this histologic end point is associated with a CP phenotype, we reproduced a lipopolysaccharide (LPS) model for PVL, I and evaluated developmental, behavioral, and motor outcomes.Study design: On gestational day 15, Fischer 344 rats were intracervically injected with .1 mg/kg LPS (n = 5) or saline (n = 4). After delivery, evaluation for developmental milestones was performed on days I to 21 (LPS = 45; control = 30 pups). Males were also tested at 2.5 months using open-field, rotarod, and anxiety tests. On day 21, 2 pups/litter were perfused for immunohistochemistry, and stained with 2 oligodendrocyte antibodies: 2', d'-cyclic nucleotide phosphodiesterase (CNP), and myelin proteolipid protein (PLP) with relative densities of staining assessed using NIH Image software. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA).Results: LPS pups demonstrated decreased CNP (P =.04) and PLP (P =.06) staining, replicating the model. There was no difference seen in neonatal weight, righting, negative geotaxis, cliff aversion, rooting, forelimb grasp, audio startle, air righting, eye opening, and activity. Surprisingly, LPS-exposed neonatal rats mastered forelimb placement (P