Dynamic structural and metabolic changes during the epileptogenesis in the pilocarpine model of temporal lobe epilepsy: A longitudinal MRI study

IF 3.2 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2026-03-15 Epub Date: 2026-01-21 DOI:10.1016/j.brainres.2026.150180

Luciana Ramalho Pimentel-Silva , Renata Barbosa , Alexandre Hilario Berenguer de Matos , Raphael Fernandes Casseb , Brunno Machado de Campos , Mônica Mingone Cordeiro , Juliana Francischinelli Casseb , Elayne Vieira Dias , Andre Schwambach Vieira , Luis Concha , Iscia Lopes-Cendes , Fernando Cendes

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Abstract

Purpose

We aimed to evaluate longitudinal structural and metabolic changes after induced status epilepticus (SE) in the pilocarpine model of TLE, over the three phases of epileptogenesis.

Methods

We analyzed 48 male eight-week-old Wistar rats assigned to sham-control and SE-induced groups. T2-weighted images and 1H-MR spectra were acquired using a 3 T MRI clinical scanner (Philips Achieva) equipped with an animal coil. We measured hippocampal volumes (dorsal-HVol) and total N-acetylaspartate ratios to total creatine (tNAA/tCr) in four points in time (MRI-scan): baseline (before pilocarpine or sham treatments), 48 h (acute phase), 15 days (silent period), and 30 days (beginning of the chronic phase) after experimental treatment. To test differences in dorsal-HVol and hippocampal tNAA/tCr we built generalized linear mixed effects models including groups (pilo-SE and control) and MRI-scan as main effects and a group*MRI-scan interaction.

Results

Pilo-SE and control animals showed similar baseline dorsal-HVol and hippocampal tNAA/tCr (both p > 0.1). Pilo-SE showed reduced dorsal-HVol and tNAA/tCr at all MRI-scans (all p < 0.001) when compared to controls. Intragroup analysis revealed that dorsal-HVol and tNAA/tCr significantly increased at 15- and 30-days (all p < 0.001) when compared to 48 h, although remaining lower than the baseline scan. There were no changes over time in sham-controls (all p > 0.4).

Conclusions

The novelty of our study was to analyze non-invasively structural and metabolic markers of hippocampal dysfunction across the three main phases of pilocarpine-induced epileptogenesis in comparison to the typical brain development over the same period. Acute dorsal hippocampal volume loss and hippocampal neuronal dysfunction are present as early as 48 h post-pilocarpine-induced SE, dynamically changing over time. This acute damage is followed by a pattern of gradual recovery throughout the silent and chronic phases of epileptogenesis, though with an offset for the pilo-SE group. A better understanding of the course of noninvasive markers of epileptogenesis and HS may contribute to stablish surrogate endpoints in interventions to treat or prevent focal epilepsy.

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匹罗卡品颞叶癫痫模型癫痫发生过程中的动态结构和代谢变化：纵向MRI研究

目的观察匹罗卡品致痫持续状态（SE）模型在癫痫发生三个阶段的纵向结构和代谢变化。方法48只8周龄雄性Wistar大鼠分为假对照组和se诱导组。使用配备动物线圈的3t MRI临床扫描仪（Philips Achieva）获得t2加权图像和1H-MR光谱。我们在四个时间点（mri扫描）测量海马体积（背侧- hvol）和总n -乙酰天冬氨酸与总肌酸的比率（tNAA/tCr）：基线（匹罗卡品或假治疗前），48小时（急性期），15天（沉默期）和实验治疗后30天（慢年期开始）。为了检验背侧hvol和海马tNAA/tCr的差异，我们建立了广义线性混合效应模型，包括组（pilot - se和对照组）和mri扫描作为主要效应，以及组与mri扫描的相互作用。结果spio - se和对照动物的基线背侧hvol和海马tNAA/tCr相似（p > 0.1）。与对照组相比，Pilo-SE在所有mri扫描中显示背部hvol和tNAA/tCr降低（均p <； 0.001）。组内分析显示，与48小时相比，15天和30天的背部hvol和tNAA/tCr显著增加（均p <； 0.001），尽管仍低于基线扫描。假药对照组没有随时间变化（p > 0.4）。结论：本研究的新颖之处在于分析了匹罗卡品诱发癫痫发生的三个主要阶段海马功能障碍的非侵入性结构和代谢标志物，并与同期的典型大脑发育进行了比较。早在匹罗卡品诱导SE后48小时，就会出现急性海马背侧体积损失和海马神经元功能障碍，并随时间动态变化。这种急性损伤之后是一种逐渐恢复的模式，贯穿癫痫发生的沉默和慢性阶段，尽管在pilot - se组中有所抵消。更好地了解癫痫发生和HS的非侵入性标志物的过程可能有助于在治疗或预防局灶性癫痫的干预措施中建立替代终点。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.