Liu Zining, Sivathamboo Shobi, Thergarajan Peravina, Gomes Flavia M, Ali Idrish, Powell Kim L, Perucca Piero, Jones Nigel C, O'Brien Terence J, Casillas-Espinosa Pablo
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Epilepsia Open. 2025 Jun;10(3):809-821. doi: 10.1002/epi4.70032. Epub 2025 Apr 28.
Cardiac structural and molecular changes are prevalent in people with chronic epilepsy, possibly contributing to an increased risk of premature mortality. However, understanding of the underlying pathophysiological mechanisms is limited. Here, we investigated the subacute and chronic changes in cardiac structure and ion channel/exchanger expression in different rodent models of temporal lobe epilepsy (TLE).
Two models of TLE were used: the kainic acid-induced post-status epilepticus (KASE) model in Wistar rats and the electrical self-sustained status epilepticus (SSSE) model in C57BL/6J mice. Heart tissue was collected at subacute (7 days post-SE) and chronic (12-16 weeks post-SE) timepoints from both models. Histological analysis for cardiac fibrosis and qPCR of ion channel/exchanger mRNA expression was performed.
Increased cardiac fibrosis was found in the KASE rats at the subacute (p = 0.016) and chronic (p = 0.003) timepoints compared with sham rats. In chronically epileptic KASE rats, mRNA expression analyses showed that Na1.5 and NCX1 were reduced in the septum (p = 0.026 and p = 0.020, respectively) compared with shams. In SSSE mice, Na1.5 was decreased in the right atrium (p = 0.039), and Ca3.2 and NCX1 were increased in the left ventricle subacutely (p = 0.033 and p = 0.003, respectively), and Na1.5 was increased in the septum at the chronic timepoint (p = 0.008), compared with the non-epileptic sham group.
Cardiac alterations at structural and molecular levels were found in both experimental rodent epilepsy models, subacutely post-SE and during the chronically epileptic timepoint. The presence of similar cardiac changes across the models, despite being different species and having different modes of epilepsy indication, suggests that these changes are a direct or indirect result of the seizures.
Epilepsy may lead to heart problems, which could raise the risk of early death, but the exact causes are unclear. This study examined heart changes in two rodent models of epilepsy. In rats, heart scarring and stiffness (fibrosis) increased both shortly after seizures and during chronic epilepsy, and the ability to produce key heart proteins was altered. In mice, similar changes in heart proteins appeared in different heart areas. These findings suggest seizures can directly or indirectly cause harmful heart changes. Understanding these effects might help improve care for people with epilepsy and reduce related heart risks.
慢性癫痫患者普遍存在心脏结构和分子变化，这可能导致过早死亡风险增加。然而，对潜在病理生理机制的了解有限。在此，我们研究了颞叶癫痫（TLE）不同啮齿动物模型中心脏结构以及离子通道/交换器表达的亚急性和慢性变化。
使用两种TLE模型：Wistar大鼠的海藻酸诱导癫痫持续状态后模型（KASE）和C57BL/6J小鼠的电持续性癫痫持续状态（SSSE）模型。在亚急性（癫痫持续状态后7天）和慢性（癫痫持续状态后12 - 16周）时间点从两个模型收集心脏组织。进行心脏纤维化的组织学分析以及离子通道/交换器mRNA表达的qPCR检测。
与假手术大鼠相比，KASE大鼠在亚急性（p = 0.016）和慢性（p = 0.003）时间点出现心脏纤维化增加。在慢性癫痫的KASE大鼠中，mRNA表达分析显示，与假手术组相比，隔膜中Na1.5和NCX1减少（分别为p = 0.026和p = 0.020）。在SSSE小鼠中，与非癫痫假手术组相比，右心房中Na1.5在亚急性时减少（p = 0.039），左心室中Ca3.2和NCX1在亚急性时增加（分别为p = 0.033和p = 0.003），慢性时间点隔膜中Na1.5增加（p = 0.008）。
在实验性啮齿动物癫痫模型中，在癫痫持续状态后亚急性和慢性癫痫发作时间点均发现了心脏在结构和分子水平上的改变。尽管模型的物种不同且癫痫诱导方式不同，但不同模型中存在相似的心脏变化，这表明这些变化是癫痫发作的直接或间接结果。
癫痫可能导致心脏问题，从而增加早死风险，但确切原因尚不清楚。本研究检查了两种癫痫啮齿动物模型中的心脏变化。在大鼠中，癫痫发作后不久以及慢性癫痫期间，心脏瘢痕形成和僵硬（纤维化）均增加，并且产生关键心脏蛋白的能力发生改变。在小鼠中，不同心脏区域出现了类似的心脏蛋白变化。这些发现表明癫痫发作可直接或间接导致有害的心脏变化。了解这些影响可能有助于改善癫痫患者的护理并降低相关心脏风险。
