van Eijsden Pieter, Notenboom Robbert G E, Wu Ona, de Graan Pierre N E, van Nieuwenhuizen Onno, Nicolay Klaas, Braun Kees P J
Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Brain Res. 2004 Dec 24;1030(1):11-8. doi: 10.1016/j.brainres.2004.09.025.
Temporal lobe epilepsy (TLE) is associated with febrile convulsions and childhood status epilepticus (SE). Since the initial precipitating injury, triggering epileptogenesis, occurs during this SE, we aimed to examine the metabolic and morphological cerebral changes during the acute phase of experimental SE noninvasively. In the rat lithium-pilocarpine model of SE, we performed quantified T(2)- and isotropic-diffusion-weighted (DW) magnetic resonance imaging (MRI) at 3 and 5 h of SE and acquired single-voxel (1)H MR spectra at 2, 4 and 6 h of SE. T(2) was globally decreased, most pronounced in the amygdala (Am) and piriformic cortex (Pi), in which also a significant decrease in apparent diffusion coefficient (ADC) was found. In contrast, ADC values increased transiently in the hippocampus (HC) and thalamus (Th). MR spectra showed a decrease in N-acetylaspartate (NAA) and choline (Cho) and an increase of lactate in a hippocampal voxel. The T(2) decrease, attributed to raised deoxyhemoglobin, and the presence of lactate both indicate a mismatch between oxygen demand and delivery. The ADC decrease, indicative of excitotoxicity, confirms that the amygdala and piriformic cortex are particularly vulnerable to lithium-pilocarpine-induced seizures. The transient ADC increase in the thalamus may reflect the breakdown of the blood-brain barrier (BBB), which is shown to occur in this region at these time points. Neuronal damage and failure of energy-dependent formation of NAA are likely causes of an observed decrease in NAA, while the decrease in Cho is possibly due to depletion of the cholinergic system. This study illustrates that relative hypoxia, excitotoxicity and concomitant neuronal damage associated with SE can be probed noninvasively with MR. These pathological phenomena are the first to contribute to the pathophysiology of spontaneous recurrent seizures in a later stage in this animal model.
颞叶癫痫（TLE）与热性惊厥和儿童癫痫持续状态（SE）相关。由于最初引发癫痫发生的损伤在这种癫痫持续状态期间出现，我们旨在非侵入性地研究实验性癫痫持续状态急性期大脑的代谢和形态学变化。在大鼠锂 - 匹罗卡品癫痫持续状态模型中，我们在癫痫持续状态3小时和5小时时进行了定量T(2)和各向同性扩散加权（DW）磁共振成像（MRI），并在癫痫持续状态2小时、4小时和6小时时获取了单体素(1)H磁共振波谱。T(2)整体降低，在杏仁核（Am）和梨状皮质（Pi）最为明显，在这些区域还发现表观扩散系数（ADC）显著降低。相比之下，海马体（HC）和丘脑（Th）中的ADC值短暂升高。磁共振波谱显示海马体单体素中N - 乙酰天门冬氨酸（NAA）和胆碱（Cho）降低，乳酸增加。T(2)降低归因于脱氧血红蛋白升高，乳酸的存在均表明氧需求与供应不匹配。ADC降低表明存在兴奋性毒性，证实杏仁核和梨状皮质特别易受锂 - 匹罗卡品诱导的癫痫发作影响。丘脑中ADC的短暂升高可能反映了血脑屏障（BBB）的破坏，在这些时间点该区域已显示会发生这种情况。神经元损伤和能量依赖性NAA形成的失败可能是观察到的NAA降低的原因，而Cho降低可能是由于胆碱能系统的消耗。本研究表明，与癫痫持续状态相关的相对缺氧、兴奋性毒性和伴随的神经元损伤可以通过磁共振进行非侵入性检测。在该动物模型的后期，这些病理现象首先促成了自发性反复癫痫发作的病理生理学过程。
