Combined fluid percussion brain injury and entorhinal cortical lesion: a model for assessing the interaction between neuroexcitation and deafferentation.
Combined fluid percussion brain injury and entorhinal cortical lesion: a model for assessing the interaction between neuroexcitation and deafferentation.
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DOI：
10.1089/neu.1994.11.641
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发表时间：
1994-12
影响因子：
4.2
通讯作者：
L. Phillips;B. Lyeth;R. Hamm;J. Povlishock
中科院分区：
文献类型：
--
作者：
L. Phillips;B. Lyeth;R. Hamm;J. Povlishock
实验室研究表明，过度的神经兴奋和传入神经阻滞有助于人类头部损伤后的长期发病率。由于目前没有创伤性脑损伤（TBI）的动物模型已被证明是结合联合收割机过度的神经兴奋和显着水平的去传入，我们开发了一个大鼠模型结合液压冲击TBI的神经兴奋与随后的内嗅皮层（EC）去传入。在此范例中，在每只大鼠中诱导中度液压冲击TBI，随后24小时后通过双侧EC损伤（BEC）。检查了六个条件：（1）液压冲击TBI 24 h后双侧EC损伤（TBEC），（2）液压冲击TBI（TBI），（3）双侧EC损伤（BEC），（4）假液压冲击TBI（SHAM），（5）TBI 24 h后单侧EC损伤（TUEC），（6）单侧EC损伤（UEC）。对前四组进行了运动评估（采用平衡木和平衡木行走测试）、认知缺陷（采用莫里斯水迷宫）和海马形态学评估（采用免疫细胞化学和电子显微镜）。TUEC和UEC组仅评估认知缺陷。TBEC损伤组的运动功能障碍大于单纯TBI或假手术组;然而，TBEC和BEC条件下的运动功能无显著差异。相对于每个单独的损伤，在组合的TBEC损伤模型中认知缺陷的幅度更大。这些认知缺陷似乎是两个实验损伤，BEC传入神经阻滞之间的TBI和TBEC侮辱中间产生的赤字添加剂。TBEC后15天的齿状回分子层的形态学分析表明，突触体蛋白阳性突触前末梢的分布与单独TBI或BEC后观察到的不同。具体而言，在TBEC损伤后，BEC损伤诱导的突触前重排的层状模式没有发生。目前的研究结果表明，轴突损伤及其伴随的传入神经阻滞，再加上创伤引起的神经兴奋，产生与TBI相关的发病率的提高。此外，他们表明，该模型可以有效地用于研究神经兴奋和突触可塑性之间的相互作用。
Laboratory studies suggest that excessive neuroexcitation and deafferentation contribute to long-term morbidity following human head injury. Because no current animal model of traumatic brain injury (TBI) has been shown to combine excessive neuroexcitation and significant levels of deafferentation, we developed a rat model combining the neuroexcitation of fluid percussion TBI with subsequent entorhinal cortical (EC) deafferentation. In this paradigm, moderate fluid percussion TBI was induced in each rat, followed 24 h later by bilateral EC lesion (BEC). Six conditions were examined: (1) fluid percussion TBI followed 24 h later by bilateral EC lesion (TBEC), (2) fluid percussion TBI (TBI), (3) bilateral EC lesion (BEC), (4) sham fluid percussion TBI (SHAM), (5) TBI followed 24 h later by unilateral EC lesion (TUEC), and (6) unilateral EC lesion (UEC). The first four groups were assessed for motor (with beam-balance and beam-walk testing) and cognitive deficits (with the Morris water maze) and hippocampal morphology (with immunocytochemistry and electron microscopy). The TUEC and UEC groups were assessed for cognitive deficits alone. Motor deficits were greater in the TBEC injury than in TBI or sham alone; however, no significant difference was observed between the TBEC and BEC conditions in motor performance. Cognitive deficits were of a greater magnitude in the combined TBEC injury model relative to each individual insult. These cognitive deficits appeared to be additive for the two experimental injuries, BEC deafferentation producing deficits intermediate between TBI and TBEC insults. Morphologic analysis of the dentate gyrus molecular layer at 15 days after TBEC showed that the distribution of synaptophysin-positive presynaptic terminals was distinct from that observed after either TBI or BEC alone. Specifically, the laminar pattern of presynaptic rearrangement induced by BEC lesion did not occur after TBEC injury. The present results show that axonal injury and its attendant deafferentation, when coupled with traumatically induced neuroexcitation, produce an enhancement of the morbidity associated with TBI. Moreover, they indicate that this model can effectively be used to study the interaction between neuroexcitation and synaptic plasticity.