“…Volumetry of the hippocampus at 7T in HS patients revealed a characteristic pattern of significant global ipsilateral hippocampal atrophy, restricted subfield losses in CA1 and CA4+DG, and no significant contralateral volume losses. These results confirm those that have been found at 3T and 4T, histological studies, as well as combined MRI‐histology investigations for patients with medically intractable TLE. The same marking scheme was used to assess the signal within the hippocampal subfields of HS, HS‐no, and control groups.…”
ACKNOWLEDGMENTSWe would like to acknowledge Joe Gati and Trevor Szekeres for development and testing of the 7T MRI protocols.
GRANT SUPPORTThis work was supported by grants from CIHR (MOP 184807) and NSERC.
RUNNING TITLE:Hippocampal sub-structures at 7T.
ABSTRACTPurpose: To provide a more detailed investigation of hippocampal subfields using ultrahigh field magnetic resonance imaging (MRI) for the identification of hippocampal pathologies in temporal lobe epilepsy.
Materials and Methods:Patients (N=13) with drug-resistant TLE (9 with HS-no, 4 HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( 2 * ) were studied between the two groups. In addition, radiological patient assessment at 7T and clinical outcomes were correlated with measured subfield changes.Results: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 and CA4DG. Volumetry also uncovered subfield atrophy in 33% of HS-no patients, which had not been detected using conventional imaging.
Conclusions:These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T may be superior to conventional (1.5T) visual inspection by a neuroradiologist in the identification of hippocampal pathologies in TLE, however difficulty remains in identifying HS-no cases by imaging.
“…Volumetry of the hippocampus at 7T in HS patients revealed a characteristic pattern of significant global ipsilateral hippocampal atrophy, restricted subfield losses in CA1 and CA4+DG, and no significant contralateral volume losses. These results confirm those that have been found at 3T and 4T, histological studies, as well as combined MRI‐histology investigations for patients with medically intractable TLE. The same marking scheme was used to assess the signal within the hippocampal subfields of HS, HS‐no, and control groups.…”
ACKNOWLEDGMENTSWe would like to acknowledge Joe Gati and Trevor Szekeres for development and testing of the 7T MRI protocols.
GRANT SUPPORTThis work was supported by grants from CIHR (MOP 184807) and NSERC.
RUNNING TITLE:Hippocampal sub-structures at 7T.
ABSTRACTPurpose: To provide a more detailed investigation of hippocampal subfields using ultrahigh field magnetic resonance imaging (MRI) for the identification of hippocampal pathologies in temporal lobe epilepsy.
Materials and Methods:Patients (N=13) with drug-resistant TLE (9 with HS-no, 4 HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( 2 * ) were studied between the two groups. In addition, radiological patient assessment at 7T and clinical outcomes were correlated with measured subfield changes.Results: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 and CA4DG. Volumetry also uncovered subfield atrophy in 33% of HS-no patients, which had not been detected using conventional imaging.
Conclusions:These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T may be superior to conventional (1.5T) visual inspection by a neuroradiologist in the identification of hippocampal pathologies in TLE, however difficulty remains in identifying HS-no cases by imaging.
“…In healthy tissue, we observed robust SorCS2 expression in neurons of the hippocampus, in agreement with its reported expression pattern in the murine brain (Hermey et al., 2004) (Figure 1A, top left). In human TLE-HS tissue, severe neuronal cell loss was visible in all hippocampal regions, with the exception of CA2, which is particularly resistant to epilepsy-driven degeneration (Figure 1A, top right) (Steve et al., 2014). Strikingly, surviving neurons in the CA2 region of TLE-HS tissue samples showed a substantial increase in SorCS2 levels, suggesting a role for SorCS2 in preventing neuron loss in the course of epilepsy (Figure 1A, bottom).Figure 1SorCS2 Is Upregulated in the Epileptic Human Brain and Plays a Protective Role in an Experimental Model of Temporal Lobe Epilepsy(A) SorCS2 immunostaining in the human control hippocampus and in the hippocampus of a patient with TLE and hippocampal sclerosis.…”
SummaryVPS10P domain receptors emerge as central regulators of intracellular protein sorting in neurons with relevance for various brain pathologies. Here, we identified a role for the family member SorCS2 in protection of neurons from oxidative stress and epilepsy-induced cell death. We show that SorCS2 acts as sorting receptor that sustains cell surface expression of the neuronal amino acid transporter EAAT3 to facilitate import of cysteine, required for synthesis of the reactive oxygen species scavenger glutathione. Lack of SorCS2 causes depletion of EAAT3 from the plasma membrane and impairs neuronal cysteine uptake. As a consequence, SorCS2-deficient mice exhibit oxidative brain damage that coincides with enhanced neuronal cell death and increased mortality during epilepsy. Our findings highlight a protective role for SorCS2 in neuronal stress response and provide a possible explanation for upregulation of this receptor seen in surviving neurons of the human epileptic brain.
“…Specifically, there is significant pyramidal cell loss in the hippocampal subfields CA1 and CA3, with lesser amounts of cell loss in CA2 (Fig. 1A and B; De Lanerolle et al, 1989; Steve et al, 2014). In the dentate hilus, many excitatory mossy cells are lost (Blüumcke et al, 2000).…”
Section: Organization and Reorganization Of Microcircuits: Anatomicmentioning
When studying the pathological mechanisms of epilepsy, there are a seemingly endless number of approaches from the ultrastructural level—receptor expression by EM—to the behavioral level—comorbid depression in behaving animals. Epilepsy is characterized as a disorder of recurrent seizures, which are defined as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain” (Fisher et al., 2005). Such abnormal activity typically does not occur in a single isolated neuron; rather, it results from pathological activity in large groups—or circuits—of neurons. Here we choose to focus on two aspects of aberrant circuits in temporal lobe epilepsy: their organization and potential mechanisms to control these pathological circuits. We also look at two scales: microcircuits, ie, the relationship between individual neurons or small groups of similar neurons, and macrocircuits, ie, the organization of large-scale brain regions. We begin by summarizing the large body of literature that describes the stereotypical anatomical changes in the temporal lobe—ie, the anatomical basis of alterations in microcircuitry. We then offer a brief introduction to graph theory and describe how this type of mathematical analysis, in combination with computational neuroscience techniques and using parameters obtained from experimental data, can be used to postulate how microcircuit alterations may lead to seizures. We then zoom out and look at the changes which are seen over large whole-brain networks in patients and animal models, and finally we look to the future.
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