A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion
A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion
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DOI：
10.1016/s0006-8993(99)01675-3
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发表时间：
1999-08-07
期刊：
影响因子：
2.9
通讯作者：
Sawada, T
中科院分区：
文献类型：
--
作者：
Uehara, H;Yoshioka, H;Sawada, T
脑室周围白质软化症是脑性瘫痪的重要原因，其特征是脑室周围白色物质的囊肿和凝固性坏死。由于尚未在小动物中建立脑室周围白质软化模型，因此有望在未成熟啮齿动物中建立新的白色物质损伤模型。新生大鼠在5日龄时双侧颈动脉闭塞，并在7日龄时进行脑神经病理学检查。22例脑组织学检查中，20例（90.9%）内囊内及周围有白色改变，包括凝固性坏死和囊性病变，仅2例有小面积脑梗死，5例在大脑皮质有缺血性神经元。双侧颈动脉闭塞（BCAO）动物皮质下白色物质的脑血流量（CBF）下降至对照组的25%左右。淀粉样前体蛋白（APP）的免疫组织化学表现出各种APP免疫反应性轴突配置文件的内囊和皮质下白色的物质，和更强的APP表达的锥体神经元在大脑皮层的BCAO大脑。这些结果表明，白色物质是更脆弱的比大脑皮层在5日龄大鼠时，CBF下降到约25%，并建议该模型是有用的研究白色物质的变化引起的脑灌注不足，在新生儿脑，因为以前的模型缺氧缺血性脑损伤的新生小鼠和大鼠显示优先易感性的灰质。还表明APP是未成熟脑的白色物质中的轻度轴突破坏的敏感标志物。(C)1999 Elsevier Science B.V.保留所有权利。
Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain. (C) 1999 Elsevier Science B.V. All rights reserved.