Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University Munich, Germany.
Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University Munich, Germany.
Neuroscience. 2019 Sep 1;415:44-58. doi: 10.1016/j.neuroscience.2019.06.031. Epub 2019 Jul 15.
Temporal lobe epilepsy is triggered by an initial insult, such as status epilepticus, that initiates the process of epilepsy development. Heat shock protein 70 (Hsp70) is a ubiquitously expressed molecular chaperone, involved in the inflammatory response that is upregulated after status epilepticus. Hsp70 has been described as an endogenous intracellular ligand of Toll-like receptor 4. It is released from damaged or necrotic tissue and by activated immune cells after an inflammatory event. So far, the time course and the pattern of epileptogenesis-associated alterations in Hsp70 expression have not been described in detail. Thus, we investigated immunohistochemical expression of Hsp70 in hippocampus, parahippocampal cortex, parietal cortex, amygdala, and thalamus following status epilepticus in a rat model of temporal lobe epilepsy. The impact of status epilepticus on Hsp70 expression varied during different phases of epileptogenesis, displaying a stronger effect in the early post-insult phase, a milder and more localized effect in the latency phase and no relevant effect in the chronic phase. Cellular-level characterization revealed that Hsp70 colocalized with the neuronal marker NeuN and with Toll-like receptor 4. No colocalization with the astrocytic marker GFAP or the microglia marker Iba1 was found. The intense neuronal Hsp70 upregulation during the early post-insult phase might contribute to the onset of excessive inflammation triggering molecular and cellular reorganization and generation of a hyperexcitable epileptic network. Therefore, development of multi-targeting strategies aiming at prevention of epileptogenesis should consider Hsp70 modulation in the early days following an epileptogenic insult.
颞叶癫痫是由初始损伤（如癫痫持续状态）引发的，这种损伤启动了癫痫发展过程。热休克蛋白 70（Hsp70）是一种广泛表达的分子伴侣，参与癫痫持续状态后的炎症反应上调。Hsp70 已被描述为 Toll 样受体 4 的内源性细胞内配体。它在炎症事件后从受损或坏死组织和激活的免疫细胞中释放。到目前为止，尚未详细描述与癫痫发生相关的 Hsp70 表达的时间过程和模式。因此，我们在颞叶癫痫大鼠模型中研究了癫痫持续状态后海马、海马旁皮质、顶叶皮质、杏仁核和丘脑中海马 Hsp70 的免疫组织化学表达。癫痫持续状态对 Hsp70 表达的影响在癫痫发生的不同阶段有所不同，在早期损伤阶段表现出更强的影响，在潜伏期表现出更温和且更局限的影响，在慢性阶段则没有相关影响。细胞水平的特征表明 Hsp70 与神经元标记物 NeuN 和 Toll 样受体 4 共定位。与星形胶质细胞标记物 GFAP 或小胶质细胞标记物 Iba1 没有共定位。在早期损伤阶段强烈的神经元 Hsp70 上调可能有助于过度炎症的发作，触发分子和细胞的重新组织并产生超兴奋性癫痫网络。因此，旨在预防癫痫发生的多靶点策略的发展应考虑在癫痫发作后早期对 Hsp70 进行调节。
