Midline brain injury in the immature rat induces sustained cognitive deficits, bihemispheric axonal injury and neurodegeneration
Midline brain injury in the immature rat induces sustained cognitive deficits, bihemispheric axonal injury and neurodegeneration
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DOI：
10.1016/j.expneurol.2008.05.009
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发表时间：
2008-09-01
影响因子：
5.3
通讯作者：
Raghupathi, Ramesh
中科院分区：
文献类型：
--
作者：
Huh, Jimmy W.;Widing, Ashley G.;Raghupathi, Ramesh
4 岁以下的婴儿和儿童在轻度、中度或重度弥漫性脑外伤 (TBI) 后患有慢性认知缺陷。有人认为，严重 TBI 后行为缺陷的潜在神经病理学基础是急性脑肿胀、蛛网膜下腔出血和轴突损伤。为了更好地了解轻中度 TBI 认知功能障碍的机制，开发了未成熟大鼠中线 TBI 闭合性头部损伤模型。在完整头骨中线缝合处受到撞击后，17 日龄的大鼠表现出短呼吸暂停时间（3-15 秒），不需要通气支持，也没有死亡，提示有轻度 TBI。与未受伤的大鼠相比，脑损伤的大鼠在受伤后第一周表现出显着的学习缺陷（P < 0.0005），并且在受伤后第三周表现出显着的学习缺陷（p < 0.005）和记忆缺陷（p < 0.05）。 6 至 72 小时之间，在受伤大脑的两个半球均观察到血脑屏障破坏、皮质下白质和丘脑广泛的创伤性轴突损伤以及皮质和海马的局灶性神经变性区域。损伤后8至18天，观察到皮层反应性星形细胞增多、皮层下白质束轴突变性、两侧半球丘脑神经元细胞体和突起的变性；然而，未受伤和受伤的大鼠大脑的皮质体积没有差异。这些数据表明，未成熟大鼠中的弥漫性 TBI 可导致神经元细胞体和轴突区室的持续退化，这可能在一定程度上导致观察到的持续认知缺陷。 (C) 2008 Elsevier Inc. 保留所有权利。
infants and children less than 4 years old suffer chronic cognitive deficits following mild, moderate or severe diffuse traumatic brain injury (TBI). It has been suggested that the underlying neuropathologic basis for behavioral deficits following severe TBI is acute brain swelling, subarachnoid hemorrhage and axonal injury. To better understand mechanisms of cognitive dysfunction in mild-moderate TBI, a closed head injury model of midline TBI in the immature rat was developed. Following an impact over the midline suture of the intact skull, 17-day-old rats exhibited short apnea times (3-15 s), did not require ventilatory support and suffered no mortality, Suggestive of mild TBI. Compared to un-injured rats, brain-injured rats exhibited significant learning deficits over the first week post-injury (P < 0.0005), and, significant learning (p < 0.005) and memory deficits (p < 0.05) in the third post-injury week. Between 6 and 72 h, blood-brain barrier breakdown, extensive traumatic axonal injury in the subcortical white matter and thalamus, and focal areas of neurodegeneration in the cortex and hippocampus were observed in both hemispheres of the injured brain. At 8 to 18 days post-injury, reactive astrocytosis in the cortex, axonal degeneration in the subcortical white matter tracts, and degeneration of neuronal cell bodies and processes in the thalamus of both hemispheres were observed; however, cortical volumes were not different between un-injured and injured rat brains. These data Suggest that diffuse TBI in the immature rat can lead to ongoing degeneration of both cell soma and axonal compartments of neurons, which may contribute, in part, to the observed Sustained cognitive deficits. (C) 2008 Elsevier Inc. All rights reserved.