This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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