Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy

Du, Fuliang; Whetsell, William O.; Abou-Khalil, B.; Blumenkopf, Bennett; Lothman, Eric W.; Schwarcz, Robert

doi:10.1016/0920-1211(93)90083-j

Cited by 310 publications

(210 citation statements)

References 61 publications

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“…Selective lesion of layer III neurons in the entorhinal cortex using focal injections of aminooxyacetic acid has been shown to disrupt inhibitory processes in the hippocampus area CA1, leading to a hypothesis postulating that partial loss of layer III entorhinal cortical neurons may contribute to reductions in feedforward inhibition in area CA1, amplifying the temporoammonic pathway (Denslow et al, 2001). In patients with TLE and in pilocarpine animal models of epilepsy, cell loss in layer III of the entorhinal cortex has been shown (Du et al, 1993(Du et al, , 1995 (supplemental Fig. 3, available at www.jneurosci.org as supplemental material).…”

Section: Discussionmentioning

confidence: 99%

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

Ang

Carlson²,

Coulter³

2006

J. Neurosci.

131

115

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Epilepsy affects 1-2% of the population, with temporal lobe epilepsy (TLE) the most common variant in adults. Clinical and experimental studies have demonstrated hippocampal involvement in the seizures underlying TLE. However, identification of specific functional deficits in hippocampal circuits associated with possible roles in seizure generation remains controversial. Significant attention has focused on anatomic and cellular alterations in the dentate gyrus. The dentate gyrus is a primary gateway regulating cortical input to the hippocampus and, thus, a possible contributor to the aberrant cortical-hippocampal interactions underlying the seizures of TLE. Alternate cortical pathways innervating the hippocampus might also contribute to seizure initiation. Despite this potential importance in TLE, these pathways have received little study. Using simultaneous voltage-sensitive dye imaging and patch-clamp recordings in slices from animals with epilepsy, we assessed the relative degree of synaptic excitation activated by multiple cortical inputs to the hippocampus. Surprisingly, dentate gyrus-mediated regulation of the relay of cortical input to the hippocampus is unchanged in epileptic animals, and input via the Schaffer collaterals is actually decreased despite reduction in Schaffer-evoked inhibition. In contrast, a normally weak direct cortical input to area CA1 of hippocampus, the temporoammonic pathway, exhibits a TLE-associated transformation from a spatially restricted, highly regulated pathway to an excitatory projection with Ͼ10-fold increased effectiveness. This dysregulated temporoammonic pathway is critically positioned to mediate generation and/or propagation of seizure activity in the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

Ang

Carlson²,

Coulter³

2006

J. Neurosci.

131

115

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“…TLE patients present with a pattern of brain damage known as Ammon's horn sclerosis (or mesial temporal sclerosis) that is typically characterized by neuronal loss in hippocampal CA1/CA3 subfields, dentate hilus, layer III of the medial EC, and amygdala (Gloor, 1991(Gloor, , 1997Houser, 1999;Du et al, 1993). Similar histopathological changes have been reported to occur in laboratory animals by injecting convulsant drugs such as pilocarpine or kainic acid, or by repetitive electrical stimulation of limbic pathways (Ben-Ari, 1985;Cavalheiro et al, 1991;Curia et al, 2008;Du et al, 1995).…”

Section: Gaba a Receptor-mediated Inhibition In Temporal Lobe Epilepsymentioning

confidence: 99%

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Avoli¹,

Curtis²

2011

Progress in Neurobiology

224

253

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GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown that GABA A receptormediated inhibition controls neuronal excitability and thus the occurrence of seizures. However, more complex, and at times unexpected, mechanisms of GABAergic signaling have been identified during epileptiform discharges over the last few years. Here, we will review experimental data that point at the paradoxical role played by GABA A receptor-mediated mechanisms in synchronizing neuronal networks, and in particular those of limbic structures such as the hippocampus, the entorhinal and perirhinal cortices, or the amygdala. After having summarized the fundamental characteristics of GABA A receptor-mediated mechanisms, we will analyze their role in the generation of network oscillations and their contribution to epileptiform synchronization. Whether and how GABA A receptors influence the interaction between limbic networks leading to ictogenesis will be also reviewed. Finally, we will consider the role of altered inhibition in the human epileptic brain along with the ability of GABA A receptor-mediated conductances to generate synchronous depolarizing events that may lead to ictogenesis in human epileptic disorders as well.

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“…On histopathology, HS is characterized by segmental neuronal loss and gliosis within the hippocampal formation,2, 3 yet postmortem studies indicate neuronal loss and gliosis is also present in a proportion of patients in the amygdala,4 entorhinal cortex,5 temporal neocortex6 and extra‐temporal neocortex 2, 7…”

Section: Introductionmentioning

confidence: 99%

Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

Adler

Blackwood

Northam

et al. 2018

Ann Clin Transl Neurol

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ObjectiveIn contrast to adult cohorts, neocortical changes in epileptic children with hippocampal damage are not well characterized. Here, we mapped multimodal neocortical markers of epilepsy‐related structural compromise in a pediatric cohort of temporal lobe epilepsy and explored how they relate to clinical factors.MethodsWe measured cortical thickness, gray–white matter intensity contrast and intracortical FLAIR intensity in 22 patients with hippocampal sclerosis (HS) and 30 controls. Surface‐based linear models assessed between‐group differences in morphological and MR signal intensity markers. Structural integrity of the hippocampus was measured by quantifying atrophy and FLAIR patterns. Linear models were used to evaluate the relationships between hippocampal and neocortical MRI markers and clinical factors.ResultsIn the hippocampus, patients demonstrated ipsilateral atrophy and bilateral FLAIR hyperintensity. In the neocortex, patients showed FLAIR signal hyperintensities and gray–white matter boundary blurring in the ipsilesional mesial and lateral temporal neocortex. In contrast, cortical thinning was minimal and restricted to a small area of the ipsilesional temporal pole. Furthermore, patients with a history of febrile convulsions demonstrated more pronounced FLAIR hyperintensity in the ipsilesional temporal neocortex.InterpretationPediatric HS patients do not yet demonstrate the widespread cortical thinning present in adult cohorts, which may reflect consequences of a protracted disease process. However, pronounced temporal neocortical FLAIR hyperintensity and blurring of the gray–white matter boundary are already detectable, suggesting that alterations in MR signal intensities may reflect a different underlying pathophysiology that is detectable earlier in the disease and more pervasive in patients with a history of febrile convulsions.

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Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy

Cited by 310 publications

References 61 publications

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Multimodal computational neocortical anatomy in pediatric hippocampal sclerosis

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