Metabolic injury in a variable rat model of post-status epilepticus.
Metabolic injury in a variable rat model of post-status epilepticus.
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作者：
Pearce PS;Wu Y;Rapuano A;Kelly KM;de Lanerolle N;Pan JW
癫痫的体内研究通常使用延长的癫痫持续状态来产生复发性癫痫发作。然而，关于可变状态持续时间的报告发现，癫痫发作40-50分钟后损伤的离散差异，表明癫痫发作持续时间的病理生理敏感性。在这份报告中，我们采取了多变量聚类分析，研究了短期癫痫持续状态模型，使用在体内的7 T磁共振波谱（MRS）和组织学评价。Hellier Dudek模型应用于45分钟的癫痫持续状态，之后在癫痫持续状态后3天和3周对动物进行两次成像。采用单个体素点分辨光谱（PRESS）MRS采集海马齿状回和CA 3区的数据，评估代谢物与总肌酸（tCr）的比值。在第二次成像研究后的动物亚组中，通过尼氏染色对脑进行组织学分析。对来自21只红藻氨酸处理动物（齿状回体素）的3天数据进行分层聚类分析，将其分为两个聚类，表示为KM（更多损伤，n = 6）和KL（较少损伤，n = 15）。虽然他们之间在红藻氨酸剂量或癫痫发作计数上没有差异，但损伤的代谢模式是不同的。KM组显示神经元和神经胶质参数的最大显著变化; KL组显示较温和但显著的变化。在3周时，KL组与对照组相比恢复正常，而KM组持续存在降低的N-乙酰天冬氨酸（NAA）/tCr、谷氨酸/tCr以及增加的肌醇/tCr和谷氨酰胺/tCr。该分类也与3周时的后续组织学模式一致。虽然短的状态期可能会产生一个连续分布的代谢损伤，这些数据表明，短Hellier Dudek模型似乎产生两个层次的损伤。在隔离组中观察到的变化持续到3周，并且可以根据与组织学结果一致的神经元和神经胶质生物标志物来解释。
In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40–50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation. The Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post–status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining. A hierarchical cluster analysis performed on the 3‐day data from 21 kainate‐treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N‐acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks. Although a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according to neuronal and glial biomarkers consistent with histology results.
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DOI：
10.1523/jneurosci.0980-08.2009
发表时间：
2009-02-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Williams PA;White AM;Clark S;Ferraro DJ;Swiercz W;Staley KJ;Dudek FE
通讯作者：
Dudek FE
影响因子：
--
作者：
Hellier, Jennifer L;Dudek, F Edward
通讯作者：
Dudek, F Edward
影响因子：
2.9
作者：
Motte, J;Fernandes, MJD;Nehlig, A
通讯作者：
Nehlig, A
影响因子：
5.6
作者：
Norwood, Braxton A.;Bauer, Sebastian;Rosenow, Felix
通讯作者：
Rosenow, Felix
影响因子：
4.4
作者：
SHANK, RP;BALDY, WJ;ASH, CW
通讯作者：
ASH, CW