Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage
Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage
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DOI：
10.1016/j.bbr.2012.03.029
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发表时间：
2012-06-15
影响因子：
2.7
通讯作者：
Coq, Jacques-Olivier
中科院分区：
文献类型：
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作者：
Delcour, Maxime;Russier, Michael;Coq, Jacques-Olivier
早产儿和低出生体重儿围产期缺氧-缺血引起的早期脑损伤，如白色物质损伤（WMD），是死亡率和慢性残疾（包括感觉、运动、行为和认知障碍）的高风险因素。在以前的研究中，我们建立了一个基于产前缺血（PI）的WMD模型，在E17通过单侧结扎孕鼠子宫动脉诱导。我们已经证明，PI重现了在早产儿中观察到的一些主要缺陷，如白色和灰质损伤、髓鞘形成缺陷、运动、感觉运动和短期记忆障碍，以及相关的肌肉骨骼和神经解剖学组织病理学[1-3]。在这里，我们确定了有害的影响，PI对成年大鼠的几个行为和认知能力，以及在各种相关的脑区的神经解剖基层。成年PI大鼠表现出自发的探索和运动多动，信息编码的缺陷，并在短期和长期的对象记忆任务的缺陷，但没有损害空间学习或工作记忆的水迷宫任务。这些结果与白色物质损伤和内嗅皮质的损伤一致，如轴突变性、星形胶质细胞增生和神经元密度所检测的。虽然穹窿、海马和扣带回皮质有星形胶质细胞增生和轴突变性，但海马和扣带回皮质的神经元密度不受PI的影响。PI大鼠的自发性多动、对象记忆任务缺陷、内侧和外侧内嗅皮质中的神经元密度以及穹窿中的星形胶质细胞增生水平与出生体重相关。因此，这种啮齿类动物模型的大规模杀伤性武器的基础上PI出现概括的主要神经行为和神经解剖学的人类赤字经常观察到的早产儿围产期缺血史。(C)2012 Elsevier B. V.保留所有权利，
Early brain damage, such as white matter damage (WMD), resulting from perinatal hypoxia-ischemia in preterm and low birth weight infants represents a high risk factor for mortality and chronic disabilities, including sensory, motor, behavioral and cognitive disorders. In previous studies, we developed a model of WMD based on prenatal ischemia (PI), induced by unilateral ligation of uterine artery at E17 in pregnant rats. We have shown that PI reproduced some of the main deficits observed in preterm infants, such as white and gray matter damage, myelination deficits, locomotor, sensorimotor, and short-term memory impairments, as well as related musculoskeletal and neuroanatomical histopathologies [1-3]. Here, we determined the deleterious impact of PI on several behavioral and cognitive abilities in adult rats, as well as on the neuroanatomical substratum in various related brain areas. Adult PI rats exhibited spontaneous exploratory and motor hyperactivity, deficits in information encoding, and deficits in short- and long-term object memory tasks, but no impairments in spatial learning or working memory in watermaze tasks. These results were in accordance with white matter injury and damage in the medial and lateral entorhinal cortices, as detected by axonal degeneration, astrogliosis and neuronal density. Although there was astrogliosis and axonal degeneration in the fornix, hippocampus and cingulate cortex, neuronal density in the hippocampus and cingulate cortex was not affected by PI. Levels of spontaneous hyperactivity, deficits in object memory tasks, neuronal density in the medial and lateral entorhinal cortices, and astrogliosis in the fornix correlated with birth weight in PI rats. Thus, this rodent model of WMD based on PI appears to recapitulate the main neurobehavioral and neuroanatomical human deficits often observed in preterm children with a perinatal history of ischemia. (C) 2012 Elsevier B.V. All rights reserved,