Posttraumatic epilepsy after controlled cortical impact injury in mice.
Posttraumatic epilepsy after controlled cortical impact injury in mice.
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DOI：
10.1016/j.expneurol.2008.10.005
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发表时间：
2009-02
影响因子：
5.3
通讯作者：
Smith BN
中科院分区：
文献类型：
--
作者：
Hunt RF;Scheff SW;Smith BN
许多患者在创伤后发生颞叶癫痫，但对头部损伤后慢性癫痫发作的基本机制仍知之甚少。使用受控皮质撞击损伤模型，我们检查了小鼠在轻度（0.5mm损伤深度）或重度（1.0mm损伤深度）脑损伤后是否发生自发性癫痫发作，以及随后的创伤后苔藓纤维发芽如何与损伤后42-71天齿状回的兴奋性相关。几周后，在20%的轻度损伤小鼠和36%的重度损伤小鼠中观察到自发行为癫痫发作。苔藓纤维发芽通常存在于损伤同侧的齿状回隔片中，但在对照组小鼠中没有。在苔藓纤维出芽的脑片上，20 ms和40 ms脉冲间隔的穿支通路刺激使齿状回颗粒细胞的双脉冲比显著降低（P<0.01），而80 ms和160 ms脉冲间隔的双脉冲比无显著降低（P> 0.05）。这些切片的特征还在于在含100μM印防己毒素的无Mg 2 + ACSF存在下，齿状回中的自发和门诱发癫痫样活动。与此相反，成对脉冲和肺门诱发的反应，从受伤的动物，没有显示苔藓纤维发芽切片与对照组没有什么不同。这些数据表明，自发性创伤后癫痫发作的发展，以及与颞叶癫痫相关的结构和功能网络的变化，在小鼠齿状回CCI损伤后71天。识别表现出与人类损伤诱导的癫痫相似病理的实验损伤模型应该有助于阐明受伤大脑变得癫痫的机制。
Many patients develop temporal lobe epilepsy after trauma, but basic mechanisms underlying the development of chronic seizures after head injury remain poorly understood. Using the controlled cortical impact injury model we examined whether mice developed spontaneous seizures after mild (0.5mm injury depth) or severe (1.0mm injury depth) brain injury and how subsequent posttraumatic mossy fiber sprouting was associated with excitability in the dentate gyrus 42–71 days after injury. After several weeks, spontaneous behavioral seizures were observed in 20% of mice with mild and 36% of mice with severe injury. Mossy fiber sprouting was typically present in septal slices of the dentate gyrus ipsilateral to the injury, but not in control mice. In slices with mossy fiber sprouting, perforant path stimulation revealed a significant reduction (P<0.01) in paired-pulse ratios in dentate granule cells at 20ms and 40ms interpulse intervals, but not at 80ms or 160ms intervals. These slices were also characterized by spontaneous and hilar-evoked epileptiform activity in the dentate gyrus in the presence of Mg2+-free ACSF containing 100μM picrotoxin. In contrast, paired-pulse and hilar-evoked responses in slices from injured animals that did not display mossy fiber sprouting were not different from controls. These data suggest the development of spontaneous posttraumatic seizures as well as structural and functional network changes associated with temporal lobe epilepsy in the mouse dentate gyrus by 71d after CCI injury. Identifying experimental injury models that exhibit similar pathology to injury-induced epilepsy in humans should help to elucidate the mechanisms by which the injured brain becomes epileptic.