CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic; Department of Neurology, St. Anne's University Hospital and Medical Faculty of Masaryk University, Pekarska 53, 656 91 Brno, Czech Republic.
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Neurobiol Dis. 2022 Jan;162:105566. doi: 10.1016/j.nbd.2021.105566. Epub 2021 Nov 24.
Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE.
颞叶癫痫（TLE）是成人中最常见的癫痫类型；它通常始于婴儿期或儿童早期。尽管 TLE 主要被认为是灰质病理学，但越来越多的证据将这种疾病与白质异常联系起来。在这项研究中，我们利用 12 日龄（P）大鼠李-匹鲁卡品诱导的 TLE 模型，探索 TLE 在未成熟大脑中的发作和进展对白质完整性和发育的影响。弥散张量成像（DTI）和 Black-Gold II 组织学揭示了在 P28 时，主要白质轨迹（胼胝体、内囊和外囊以及深部脑白质）在整个大脑中扩散的中断。这些异常在 TLE 诱导后三个月内大多不再存在，只有外囊和深部脑白质仍存在有限的异常。在四阶旋转框架中的虚构场中的弛豫表明，在 P28 和 P72 两个时间点观察到的白质变化与髓鞘含量降低一致。受 TLE 诱导的白质异常影响的动物在成年时表现出丘脑与内侧前额叶和体感皮层之间的功能连接增加。此外，在 P15 和 P18 时对额外的动物组进行的组织学分析显示，白质完整性只有轻微变化，这表明 TLE 进展的年龄依赖性影响逐渐增强。总之，未成熟大脑中的 TLE 进展会扭曲白质发育，在 P28 左右达到高峰，随后在成年后会有很大的恢复。这种发育延迟可能导致与早期 TLE 相关的认知和行为合并症。
