TEMPORAL LOBE EPILEPSY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目标是评估颞叶癫痫中发生的能量变化的起源、程度和意义，并将其与其他组织学和生理学指标相关联。 区域能源关系： 以前，我们发现，有一个前-后梯度下降的PCr/ATP，与前足和杏仁核比身体更严重的损害，而这些地区之间没有精力充沛的差异被视为在控制数据。虽然A-P梯度在同侧海马中最清楚，但在对侧海马中也存在类似的梯度。 我们还分析了来自双侧纹状体的能量数据，并将受试者内的区域值关联起来。同侧丘脑与对侧海马结构（R=0.55，p<0.02）、同侧丘脑与双侧纹状体核（同侧，R=0.48，p<0.05;对侧，R =0.54，p<0.02）之间存在显著的线性相关。这与癫痫的网络观点一致，其中生物能量异常可能沿着癫痫传播的路径传播。 1H光谱成像和与神经病理学发现的关系： 与31 P数据相似，我们之前已经观察到同侧和对侧小脑顶的NAA/Cr值存在明显的后-前梯度，越向前下降越大。为了进一步研究这一点，我们评估了活化星形胶质细胞的GFAP染色和NAA/Cr之间的关系。统计学上显著的线性相关性之间的平均同侧NAA/Cr（沿海马结构沿着5个位置的平均值）和GFAP染色在CA 1，CA 2，CA 3和CA 4，但不齿状。然而，与31 P数据相似，斯皮尔曼秩序分析和对数分析均显示海马NAA/Cr平均数据与齿状回GFAP染色显著相关（R=0.71，p<0.01）。 这再次表明，通过海马NAA/Cr测量评估的神经元损伤更能反映下游过程。与CA部门的显着的线性关系，结合与齿状高度显着的对数关系是一致的，认为神经元损伤发生在齿状苔藓纤维发芽下游。因此，看来，过去的齿状损伤的个体差异是光谱测量的神经元损伤的一个重要的致病因素，也是一致的齿状作为一个“看门人”在癫痫发作传播。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to evaluate the origin, extent and significance of the energetic changes that occur in temporal lobe epilepsy and correlate them with other histological and phsyiological measures. Regional Energetic Relationships: Previously, we found that there is an anterior-posterior gradient in the decline of PCr/ATP, with the anterior pes and amygdala being more severely compromised than the body, while no energetic differences between these regions were seen in control data. While the A-P gradient was most clearly seen in the ipsilateral hippocampus, a similar gradient was also present in the contralateral hippocampus. We also analyzed the energetic data from the bilateral striatum and correlated the regional values within subjects. Significant linear correlations were seen between the ipsilateral thalamus to the contralateral hippocampal formation (R=0.55, p<0.02), as well as between the ipsilateral thalamus to bilateral striate nuclei (ipsilateral, R=0.48, p<0.05, contralateral, R=0.54, p<0.02). This is consistent with a network view of epilepsy, wherein bioenergetic abnormalities are propagated possibly along the path of seizure dissemination. 1H Spectroscopic Imaging and Relationship to Neuropathological Findings: Similar to the 31P data, we have previously seen a marked posterior-anterior gradient in NAA/Cr values in the ipsi- and contralateral hippocampi, with greater decreases more anteriorly. To investigate this further we evaluated the relationship between GFAP staining for activated astrocytes and NAA/Cr. Statistically significant linear correlations were seen between the mean ipsilateral NAA/Cr (average of five locations along the hippocampal formation) and GFAP staining in the CA1, CA2, CA3 and CA4, but not dentate. However, similar to the 31P data, both a Spearman rank-order analysis and a logarithmic analysis show a significant relationship for the mean hippocampal NAA/Cr data and the dentate GFAP staining (R=0.71, p<0.01). This again suggests that the neuronal damage as evaluated by the hippocampal NAA/Cr measurement is more reflective of a downstream process. The significant linear relationships with the CA sectors, in conjunction with the highly significant logarithmic relationship with the dentate are consistent with the view that the neuronal damage occurs downstream to the dentate mossy fiber sprouting. It thus appears that individual variability in damage past the dentate is an important causative factor to the spectroscopically measured neuronal injury and is also consistent with the dentate functioning as a "gatekeeper" in seizure propagation.