scholarly journals A comparative study of the dentate gyrus in hippocampal sclerosis in epilepsy and dementia

2014 ◽  
Vol 40 (2) ◽  
pp. 177-190 ◽  
Author(s):  
R. Bandopadhyay ◽  
J. Y. W. Liu ◽  
S. M. Sisodiya ◽  
M. Thom
2009 ◽  
Vol 111 (6) ◽  
pp. 1237-1247 ◽  
Author(s):  
László Seress ◽  
Hajnalka Ábrahám ◽  
Zsolt Horváth ◽  
Tamás Dóczi ◽  
József Janszky ◽  
...  

Object Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Methods Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Results Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. Conclusions In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.


2015 ◽  
Vol 52 (6) ◽  
pp. 1183-1186 ◽  
Author(s):  
A. Klang ◽  
D. Thaller ◽  
P. Schmidt ◽  
G. G. Kovacs ◽  
P. Halasz ◽  
...  

2015 ◽  
Vol 11 (7S_Part_12) ◽  
pp. P563-P563
Author(s):  
Maria Sagrario Manzano Palomo ◽  
Maria Jose Gil Moreno ◽  
Maria De La Luz Cuadrado Perez ◽  
Alberto Rabano

2008 ◽  
Vol 115 (6) ◽  
pp. 697-700 ◽  
Author(s):  
M. Thom ◽  
L. Martinian ◽  
L. O. Caboclo ◽  
A. W. McEvoy ◽  
S. M. Sisodiya

Seizure ◽  
2015 ◽  
Vol 27 ◽  
pp. 75-79 ◽  
Author(s):  
L. D’Alessio ◽  
H. Konopka ◽  
E. Escobar ◽  
A. Acuña ◽  
S. Oddo ◽  
...  

2014 ◽  
Vol 44 (14) ◽  
pp. 3037-3049 ◽  
Author(s):  
M. Thom ◽  
M. Kensche ◽  
J. Maynard ◽  
J. Liu ◽  
C. Reeves ◽  
...  

BackgroundDe novointerictal psychosis, albeit uncommon, can develop in patients following temporal lobe surgery for epilepsy. Pathological alterations of the dentate gyrus, including cytoarchitectural changes, immaturity and axonal reorganization that occur in epilepsy, may also underpin co-morbid psychiatric disorders. Our aim was to study candidate pathways that may be associated with the development of interictal psychosis post-operatively in patients with hippocampal sclerosis (HS).MethodA total of 11 patients with HS who developed interictal psychosis (HS-P) post-operatively were compared with a matched surgical HS group without psychosis (HS-NP). Resected tissues were investigated for the extent of granule cell dispersion, mossy fibre sprouting and calbindin expression in the granule cells. We quantified doublecortin, mini-chromosome maintenance protein 2 (MCM2) and reelin-expressing neuronal populations in the dentate gyrus as well as the distribution of cannabinoid type 1 receptor (CBR1).ResultsThe patterns of neuronal loss and gliosis were similar in both groups. HS-P patients demonstrated less mossy fibre sprouting and granule cell dispersion (p < 0.01) and more frequent reduction in calbindin expression in granule cells. There were no group differences in the densities of immature MCM2, doublecortin and reelin-positive cells. CBR1 labelling was significantly lower in Cornu ammonis area CA4 relative to other subfields (p < 0.01); although reduced staining in all hippocampal regions was noted in HS-P compared with HS-NP patients, the differences were not statistically significant.ConclusionsThe alterations in dentate gyrus pathology found in HS-P patients could indicate underlying differences in the cellular response to seizures. These mechanisms may predispose to the development of psychosis in epilepsy and warrant further investigation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wenbiao Xiao ◽  
Zhiquan Yang ◽  
Xiaoxin Yan ◽  
Li Feng ◽  
Lili Long ◽  
...  

Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment, and mostly presents with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis (HS). However, the underlying molecular mechanisms involved remain poorly characterized. The dentate gyrus (DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, a isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technique was performed for the analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from autopsy. Our proteomic data identified 5,583 proteins, of which 82 proteins were upregulated and 90 proteins were downregulated. Bioinformatics analysis indicated that differentially expressed proteins were enriched in “synaptic vesicle,” “mitochondrion,” “cell-cell adhesion,” “regulation of synaptic plasticity,” “ATP binding,” and “oxidative phosphorylation.” Protein-protein interaction network analysis found a pivotal module of 10 proteins that were related to “oxidative phosphorylation.” This study has investigated proteomic alterations in the DG region of TLE-HS patients, and paved the way for the better understanding of epileptogenesis mechanisms and future therapeutic intervention.


2020 ◽  
Vol 123 (1) ◽  
pp. 392-406 ◽  
Author(s):  
Ahmad Alhourani ◽  
Kenneth N. Fish ◽  
Thomas A. Wozny ◽  
Vivek Sudhakar ◽  
Ronald L. Hamilton ◽  
...  

Medically intractable temporal lobe epilepsy is a devastating disease, for which surgical removal of the seizure onset zone is the only known cure. Multiple studies have found evidence of abnormal dentate gyrus network circuitry in human mesial temporal lobe epilepsy (MTLE). Principal neurons within the dentate gyrus gate entorhinal input into the hippocampus, providing a critical step in information processing. Crucial to that role are GABA-expressing neurons, particularly parvalbumin (PV)-expressing basket cells (PVBCs) and chandelier cells (PVChCs), which provide strong, temporally coordinated inhibitory signals. Alterations in PVBC and PVChC boutons have been described in epilepsy, but the value of these studies has been limited due to methodological hurdles associated with studying human tissue. We developed a multilabel immunofluorescence confocal microscopy and a custom segmentation algorithm to quantitatively assess PVBC and PVChC bouton densities and to infer relative synaptic protein content in the human dentate gyrus. Using en bloc specimens from MTLE subjects with and without hippocampal sclerosis, paired with nonepileptic controls, we demonstrate the utility of this approach for detecting cell-type specific synaptic alterations. Specifically, we found increased density of PVBC boutons, while PVChC boutons decreased significantly in the dentate granule cell layer of subjects with hippocampal sclerosis compared with matched controls. In contrast, bouton densities for either PV-positive cell type did not differ between epileptic subjects without sclerosis and matched controls. These results may explain conflicting findings from previous studies that have reported both preserved and decreased PV bouton densities and establish a new standard for quantitative assessment of interneuron boutons in epilepsy. NEW & NOTEWORTHY A state-of-the-art, multilabel immunofluorescence confocal microscopy and custom segmentation algorithm technique, developed previously for studying synapses in the human prefrontal cortex, was modified to study the hippocampal dentate gyrus in specimens surgically removed from patients with temporal lobe epilepsy. The authors discovered that chandelier and basket cell boutons in the human dentate gyrus are differentially altered in mesial temporal lobe epilepsy.


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