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1.
Front Synaptic Neurosci ; 15: 1233569, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37635750

RESUMO

Epilepsy is a prevalent neurological condition, with underlying neuronal mechanisms involving hyperexcitability and hypersynchrony. Imbalance between excitatory and inhibitory circuits, as well as histological reorganization are relatively well-documented in animal models or even in the human hippocampus, but less is known about human neocortical epileptic activity. Our knowledge about changes in the excitatory signaling is especially scarce, compared to that about the inhibitory cell population. This study investigated the firing properties of single neurons in the human neocortex in vitro, during pharmacological blockade of glutamate receptors, and additionally evaluated anatomical changes in the excitatory circuit in tissue samples from epileptic and non-epileptic patients. Both epileptic and non-epileptic tissues exhibited spontaneous population activity (SPA), NMDA receptor antagonization reduced SPA recurrence only in epileptic tissue, whereas further blockade of AMPA/kainate receptors reversibly abolished SPA emergence regardless of epilepsy. Firing rates did not significantly change in excitatory principal cells and inhibitory interneurons during pharmacological experiments. Granular layer (L4) neurons showed an increased firing rate in epileptic compared to non-epileptic tissue. The burstiness of neurons remained unchanged, except for that of inhibitory cells in epileptic recordings, which decreased during blockade of glutamate receptors. Crosscorrelograms computed from single neuron discharge revealed both mono- and polysynaptic connections, particularly involving intrinsically bursting principal cells. Histological investigations found similar densities of SMI-32-immunopositive long-range projecting pyramidal cells in both groups, and shorter excitatory synaptic active zones with a higher proportion of perforated synapses in the epileptic group. These findings provide insights into epileptic modifications from the perspective of the excitatory system and highlight discrete alterations in firing patterns and synaptic structure. Our data suggest that NMDA-dependent glutamatergic signaling, as well as the excitatory synaptic machinery are perturbed in epilepsy, which might contribute to epileptic activity in the human neocortex.

2.
Biomedicines ; 10(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36009358

RESUMO

Cannabidiol (CBD) showed anticonvulsant action in several preclinical models and is currently approved by regulatory agencies to treat childhood epilepsy syndromes. However, CBD treatment has limited benefits, and its long-term effects on cognition are not fully understood yet. This study aimed to examine the impact of long-term CBD treatment in the pentylenetetrazole (PTZ)-kindling model of epilepsy. Adult male Wistar rats (N = 24) received PTZ (35 mg/kg intraperitoneally) every other day until two consecutive generalized seizures occurred. CBD (60 mg/kg body weight) was administered daily by the oral route until the kindled state was achieved (n = 12). To confirm that the formulation and administration techniques were not of concern, liquid chromatography-mass spectrometry was performed to test the brain penetration of the CBD formula. As a result of CBD treatment, a lower mortality rate and significantly prolonged generalized seizure latency (925.3 ± 120.0 vs. 550.1 ± 69.62 s) were observed, while the frequency and duration of generalized seizures were not influenced. The CBD-treated group showed a significant decrease in vertical exploration in the open field test and a significant decrease in the discrimination index in the novel object recognition (NOR) test (-0.01 ± 0.17 vs. 0.57 ± 0.15, p = 0.04). The observed behavioral characteristics may be connected to the decreased thickness of the stratum pyramidale or the decreased astrogliosis observed in the hippocampus. In conclusion, CBD treatment did not prevent kindling, nor did it affect seizure frequency or duration. However, it did increase the latency to the first seizure and decreased the prolonged status epilepticus-related mortality in PTZ-kindled rats. The cognitive impairment observed in the NOR test may be related to the high dose used in this study, which may warrant further investigation.

3.
Front Neuroinform ; 16: 851024, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769832

RESUMO

The meaning behind neural single unit activity has constantly been a challenge, so it will persist in the foreseeable future. As one of the most sourced strategies, detecting neural activity in high-resolution neural sensor recordings and then attributing them to their corresponding source neurons correctly, namely the process of spike sorting, has been prevailing so far. Support from ever-improving recording techniques and sophisticated algorithms for extracting worthwhile information and abundance in clustering procedures turned spike sorting into an indispensable tool in electrophysiological analysis. This review attempts to illustrate that in all stages of spike sorting algorithms, the past 5 years innovations' brought about concepts, results, and questions worth sharing with even the non-expert user community. By thoroughly inspecting latest innovations in the field of neural sensors, recording procedures, and various spike sorting strategies, a skeletonization of relevant knowledge lays here, with an initiative to get one step closer to the original objective: deciphering and building in the sense of neural transcript.

4.
Cells ; 10(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804543

RESUMO

Temporal lobe epilepsy (TLE) is characterized by changes in interneuron numbers in the hippocampus. Deep brain stimulation (DBS) is an emerging tool to treat TLE seizures, although its mechanisms are not fully deciphered. We aimed to depict the effect of amygdala DBS on the density of the most common interneuron types in the CA1 hippocampal subfield in the lithium-pilocarpine model of epilepsy. Status epilepticus was induced in male Wistar rats. Eight weeks later, a stimulation electrode was implanted to the left basolateral amygdala of both pilocarpine-treated (Pilo, n = 14) and age-matched control rats (n = 12). Ten Pilo and 4 control animals received for 10 days 4 daily packages of 50 s 4 Hz regular stimulation trains. At the end of the stimulation period, interneurons were identified by immunolabeling for parvalbumin (PV), neuropeptide Y (NPY), and neuronal nitric oxide synthase (nNOS). Cell density was determined in the CA1 subfield of the hippocampus using confocal microscopy. We found that PV+ cell density was preserved in pilocarpine-treated rats, while the NPY+/nNOS+ cell density decreased significantly. The amygdala DBS did not significantly change the cell density in healthy or in epileptic animals. We conclude that DBS with low frequency applied for 10 days does not influence interneuron cell density changes in the hippocampus of epileptic rats.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Epilepsia/genética , Hipocampo/fisiopatologia , Interneurônios/metabolismo , Pilocarpina/metabolismo , Animais , Masculino , Ratos , Ratos Wistar
5.
Brain Sci ; 10(11)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202818

RESUMO

Temporal-lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and warrants the development of new therapies, such as deep-brain stimulation (DBS). DBS was applied to different brain regions for patients with epilepsy; however, the mechanisms of action are not fully understood. Therefore, we tried to characterize the effect of amygdala DBS on hippocampal electrical activity in the lithium-pilocarpine model in male Wistar rats. After status epilepticus (SE) induction, seizure patterns were determined based on continuous video recordings. Recording electrodes were inserted in the left and right hippocampus and a stimulating electrode in the left basolateral amygdala of both Pilo and age-matched control rats 10 weeks after SE. Daily stimulation protocol consisted of 4 × 50 s stimulation trains (4-Hz, regular interpulse interval) for 10 days. The hippocampal electroencephalogram was analyzed offline: interictal epileptiform discharge (IED) frequency, spectral analysis, and phase-amplitude coupling (PAC) between delta band and higher frequencies were measured. We found that the seizure rate and duration decreased (by 23% and 26.5%) and the decrease in seizure rate correlated negatively with the IED frequency. PAC was elevated in epileptic animals and DBS reduced the pathologically increased PAC and increased the average theta power (25.9% ± 1.1 vs. 30.3% ± 1.1; p < 0.01). Increasing theta power and reducing the PAC could be two possible mechanisms by which DBS may exhibit its antiepileptic effect in TLE; moreover, they could be used to monitor effectiveness of stimulation.

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