Golarai G, Greenwood A C, Feeney D M, Connor J A
Department of Neurosciences, University of New Mexico, Albuquerque, New Mexico 87131-5223, USA.
J Neurosci. 2001 Nov 1;21(21):8523-37. doi: 10.1523/JNEUROSCI.21-21-08523.2001.
Epilepsy is a common outcome of traumatic brain injury (TBI), but the mechanisms of posttraumatic epileptogenesis are poorly understood. One clue is the occurrence of selective hippocampal cell death after fluid-percussion TBI in rats, consistent with the reported reduction of hippocampal volume bilaterally in humans after TBI and resembling hippocampal sclerosis, a hallmark of temporal-lobe epilepsy. Other features of temporal-lobe epilepsy, such as long-term seizure susceptibility, persistent hyperexcitability in the dentate gyrus (DG), and mossy fiber synaptic reorganization, however, have not been examined after TBI. To determine whether TBI induces these changes, we used a well studied model of TBI by weight drop on somatosensory cortex in adult rats. First, we confirmed an early and selective cell loss in the hilus of the DG and area CA3 of hippocampus, ipsilateral to the impact. Second, we found persistently enhanced susceptibility to pentylenetetrazole-induced convulsions 15 weeks after TBI. Third, by applying GABA(A) antagonists during field-potential and optical recordings in hippocampal slices 3 and 15 weeks after TBI, we unmasked a persistent, abnormal APV-sensitive hyperexcitability that was bilateral and localized to the granule cell and molecular layers of the DG. Finally, using Timm histochemistry, we detected progressive sprouting of mossy fibers into the inner molecular layers of the DG bilaterally 2-27 weeks after TBI. These findings are consistent with the development of posttraumatic epilepsy in an animal model of impact head injury, showing a striking similarity to the enduring behavioral, functional, and structural alterations associated with temporal-lobe epilepsy.
癫痫是创伤性脑损伤（TBI）的常见后果，但创伤后癫痫发生的机制尚不清楚。一条线索是大鼠液压冲击性脑损伤后海马选择性细胞死亡的发生，这与报道的人类脑损伤后双侧海马体积减小一致，且类似于颞叶癫痫的标志——海马硬化。然而，颞叶癫痫的其他特征，如长期癫痫易感性、齿状回（DG）持续的过度兴奋性以及苔藓纤维突触重组，在脑损伤后尚未得到研究。为了确定脑损伤是否会引发这些变化，我们使用了一种经过充分研究的成年大鼠体感皮层重物坠落致脑损伤模型。首先，我们证实了撞击同侧DG门区和海马CA3区早期出现选择性细胞丢失。其次，我们发现脑损伤15周后对戊四氮诱导惊厥的易感性持续增强。第三，在脑损伤后3周和15周的海马切片场电位和光学记录过程中应用GABA(A)拮抗剂，我们揭示了一种持续的、异常的对APV敏感的过度兴奋性，其双侧存在且定位于DG的颗粒细胞层和分子层。最后，使用Timm组织化学方法，我们在脑损伤后2 - 27周检测到双侧DG内分子层苔藓纤维的渐进性发芽。这些发现与撞击性头部损伤动物模型中创伤后癫痫的发展一致，显示出与颞叶癫痫相关的持久行为、功能和结构改变有显著相似性。
