Different patterns of epileptiform-like activity are generated in the sclerotic hippocampus from patients with drug-resistant temporal lobe epilepsy

Abstract

Human hippocampal slice preparations from patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) are excellent material for the characterization of epileptiform-like activity. However, it is still unknown if hippocampal regions as cornu Ammonis (CA) 1, CA3 and CA4, generate population epileptiform-like activity. Here, we investigated epileptiform activities of the subiculum, CA1, CA2, CA3, CA4 (induced by elevation of extracellular potassium concentration) and the dentate gyrus (induced with hilar stimulation and elevation of potassium concentration) from sclerotic hippocampi of patients with drug-resistant TLE. Five types of epileptiform-like activity were observed: interictal-like events; periodic ictal spiking; seizure-like events; spreading depression-like events; tonic seizure-like events and no activity. Different susceptibilities to generate epileptiform activity among hippocampal regions were observed; the dentate gyrus was the most susceptible region followed by the subiculum, CA4, CA1, CA2 and CA3. The incidence of epileptiform activity pattern was associated with specific regions of the hippocampal formation. Moreover, it was observed that each region of the hippocampal formation exhibits frequency-specific ranges in each subfield of the sclerotic human tissue. In conclusion, this study demonstrates that epileptiform-like activity may be induced in different regions of the hippocampal formation, including regions that are severely affected by neuronal loss.

Activation of nicotinamide adenine dinucleotide phosphate oxidase is the primary trigger of epileptic seizures in rodent models

“…3 A lack of knowledge on molecular mechanism of seizure initiation impedes the development of targeted seizure therapy, and modern antiseizure drugs therefore mostly target general brain excitability. [6][7][8][9][10][11] Similar seizure onset was also reported for most ex vivo animal models using various seizure-inducing protocols, [12][13][14] for human brain slices, [15][16][17] and for in vivo acute and chronic animal models. 5 The LVF activity pattern occurs in the majority of seizures and often starts with a high-amplitude spike (sentinel spike) followed by a pronounced DC shift.…”

“…The LVF activity pattern occurs in the majority of seizures and often starts with a high‐amplitude spike (sentinel spike) followed by a pronounced DC shift . Similar seizure onset was also reported for most ex vivo animal models using various seizure‐inducing protocols, for human brain slices, and for in vivo acute and chronic animal models . The critical issue for understanding the seizure onset is what processes associated with the sentinel spike may trigger the following DC shift and the subsequent seizure.…”

Region‐specific differences and areal interactions underlying transitions in epileptiform activity

“…Also, a study of resected human sclerotic hippocampal tissue found that sustained ictal‐like events were almost never recorded in the CA territories (Reyes‐Garcia et al . ). We have yet to explore the subicular and parasubicular territories.…”

“…In contrast, slices that also included entorhinal cortex and neocortical territories showed ictal-like events relayed into the hippocampus from the entorhinal cortex. Also, a study of resected human sclerotic hippocampal tissue found that sustained ictal-like events were almost never recorded in the CA territories (Reyes-Garcia et al 2018). We have yet to explore the subicular and parasubicular territories.…”

Multimodal mapping and analysis of the cyto- and receptorarchitecture of the human hippocampus

“…The hippocampal formation is characterized by a heterogeneous regional and laminar cyto-and receptorarchitecture which is tightly associated with segregated input, output and intrinsic fibre systems. Furthermore, the different hippocampal regions and/or layers are differentially involved in diverse aspects of memory formation and retrieval processes (Hunsaker et al 2008;Ji and Maren 2008;Bartsch et al 2011;Coras et al 2014;Ledergerber and Moser 2017;Roy et al 2017), and display a selective vulnerability to disease (Thal et al 2000;Braak et al 2006;Kerchner et al 2012;Reyes-Garcia et al 2018), as well as differential responses to pharmacological interventions and to endogenous substances (Lynch and Bliss 1986;Yamada et al 2003;Kobayashi et al 2004;Knox et al 2011;Trieu et al 2015). However, the exact mechanisms by which the specific molecular structure and wiring pattern of a hippocampal region underpins its functionality remain elusive.…”