Dataset Information

Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy.

ABSTRACT: The endocannabinoid system (ECS) is related to several physiological processes, associated to the modulation of brain excitability, with impact in the expression of susceptibility and control of epileptic seizures. The cannabinoid receptor type 1 (CB1R) is widely expressed in the brain, especially in forebrain limbic structures. Changes in CB1R expression are associated with epileptic seizures in animal models and humans. The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy capable of mimicking tonic-clonic and limbic seizures in response to intense sound stimulation. The WAR strain presents several behavioral and physiological alterations associated with seizure susceptibility, but the ECS has never been explored in this strain. Therefore, the aim of the present study was to characterize CB1R expression in forebrain limbic structures important to limbic seizure expression in WARs. We used a detailed anatomical analysis to assess the effects of acute and chronic audiogenic seizures on CB1R expression in several layers and regions of hippocampus and amygdala. WARs showed increased CB1R immunostaining in the inner molecular layer of the hippocampus, when compared to control Wistar rats. Acute and chronic audiogenic seizures increased CB1R immunostaining in several regions of the dorsal hippocampus and amygdala of WARs. Also, changes in CB1R expression in the amygdala, but not in the hippocampus, were associated with limbic recruitment and limbic seizure severity in WARs. Our results suggest that endogenous alterations in CB1R immunostaining in WARs could be associated with genetic susceptibility to audiogenic seizures. We also demonstrated CB1R neuroplastic changes associated with acute and chronic seizures in the amygdala and hippocampus. Moreover, the present study brings important information regarding CB1R and seizure susceptibility in a genetic model of seizures and supports the relationship between ECS and epilepsy.

SUBMITTER: Lazarini-Lopes W

PROVIDER: S-EPMC7779524 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy.

Lazarini-Lopes Willian W da Silva-Júnior Rui M P RMP Servilha-Menezes Gabriel G Do Val-da Silva Raquel A RA Garcia-Cairasco Norberto N

Frontiers in behavioral neuroscience 20201221

The endocannabinoid system (ECS) is related to several physiological processes, associated to the modulation of brain excitability, with impact in the expression of susceptibility and control of epileptic seizures. The cannabinoid receptor type 1 (CB1R) is widely expressed in the brain, especially in forebrain limbic structures. Changes in CB1R expression are associated with epileptic seizures in animal models and humans. The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy capa ...[more]

PMID: 33408620

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Project description:The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the transition to seizure is complex, potentially leading to imprecise delineation of epileptogenic brain areas. In particular, the pattern of interneuronal firing at seizure onset remains under debate, with some studies demonstrating increased firing and others suggesting reductions. Previous study of neocortical sites suggests that seizure recruitment occurs upon failure of inhibition, with intact feedforward inhibition in non-recruited territories. We investigated whether the same principle applies in limbic structures. We analysed simultaneous electrocorticography (ECoG) and neuronal recordings of 34 seizures in a cohort of 19 patients (10 male, 9 female) undergoing surgical evaluation for pharmacoresistant focal epilepsy. A clustering approach with five quantitative metrics computed from ECoG and multiunit data was used to distinguish three types of site-specific activity patterns during seizures, which at times co-existed within seizures. Overall, 156 single units were isolated, subclassified by cell-type and tracked through the seizure using our previously published methods to account for impacts of increased noise and single-unit waveshape changes caused by seizures. One cluster was closely associated with clinically defined seizure onset or spread. Entrainment of high-gamma activity to low-frequency ictal rhythms was the only metric that reliably identified this cluster at the level of individual seizures (P < 0.001). A second cluster demonstrated multi-unit characteristics resembling those in the first cluster, without concomitant high-gamma entrainment, suggesting feedforward effects from the seizure. The last cluster captured regions apparently unaffected by the ongoing seizure. Across all territories, the majority of both excitatory and inhibitory neurons reduced (69.2%) or ceased firing (21.8%). Transient increases in interneuronal firing rates were rare (13.5%) but showed evidence of intact feedforward inhibition, with maximal firing rate increases and waveshape deformations in territories not fully recruited but showing feedforward activity from the seizure, and a shift to burst-firing in seizure-recruited territories (P = 0.014). This study provides evidence for entrained high-gamma activity as an accurate biomarker of ictal recruitment in limbic structures. However, reduced neuronal firing suggested preserved inhibition in mesial temporal structures despite simultaneous indicators of seizure recruitment, in contrast to the inhibitory collapse scenario documented in neocortex. Further study is needed to determine if this activity is ubiquitous to hippocampal seizures or indicates a 'seizure-responsive' state in which the hippocampus is not the primary driver. If the latter, distinguishing such cases may help to refine the surgical treatment of mesial temporal lobe epilepsy.

Project description:ImportanceSeizures are believed to be common presenting symptoms in neonates and children with spontaneous intracerebral hemorrhage (ICH). However, few data are available on the epidemiology of acute symptomatic seizures or the risk for later epilepsy.ObjectiveTo define the incidence of and explore risk factors for seizures and epilepsy in children with spontaneous ICH. Our a priori hypotheses were that younger age at presentation, cortical involvement of ICH, acute symptomatic seizures after presentation, ICH due to vascular malformation, and elevated intracranial pressure requiring urgent intervention would predict remote symptomatic seizures and epilepsy.DesignProspective cohort study conducted between March 1, 2007, and January 1, 2012.SettingThree tertiary care pediatric hospitals.ParticipantsSeventy-three pediatric subjects with spontaneous ICH including 20 perinatal (≥37 weeks' gestation to 28 days) and 53 childhood subjects (>28 days to <18 years at presentation).Main outcome measuresAcute symptomatic seizures (clinically evident and electrographic-only seizures within 7 days), remote symptomatic seizures, and epilepsy.ResultsAcute symptomatic seizures occurred in 35 subjects (48%). Acute symptomatic seizures as a presenting symptom of ICH occurred in 12 perinatal (60%) and 19 childhood (36%) subjects (P = .07). Acute symptomatic seizures after presentation occurred in 7 children. Electrographic-only seizures were present in 9 of 32 subjects (28%) with continuous electroencephalogram monitoring. One-year and 2-year remote symptomatic seizure-free survival rates were 82% (95% CI, 68-90) and 67% (95% CI, 46-82), respectively. One-year and 2-year epilepsy-free survival rates were 96% (95% CI, 83-99) and 87% (95% CI, 65-95), respectively. Elevated intracranial pressure requiring acute intervention was a risk factor for seizures after presentation (P = .01; Fisher exact test), remote symptomatic seizures, and epilepsy (P = .03, and P = .04, respectively; log-rank test).Conclusions and relevancePresenting seizures are common in perinatal and childhood ICH. Continuous electroencephalography may detect electrographic seizures in some subjects. Single remote symptomatic seizures occur in many, and development of epilepsy is estimated to occur in 13% of patients at 2 years. Elevated intracranial pressure requiring acute intervention is a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy.

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Dataset Information

Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy.

Publications

Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy.

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