scholarly journals Levetiracetam and N-Cadherin Antibody Alleviate Brain Pathology Without Reducing Early Epilepsy Development After Focal Non-convulsive Status Epilepticus in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Una Avdic ◽  
Matilda Ahl ◽  
My Andersson ◽  
Christine T. Ekdahl
Keyword(s):  
Status Epilepticus ◽  
Microglial Activation ◽  
Morphological Changes ◽  
Epileptiform Activity ◽  
Neuronal Cell ◽  
Additional Treatment ◽  
Epileptic Focus ◽  
Convulsive Status Epilepticus ◽  
Brain Pathology ◽  
Clinical Value

Focal non-convulsive status epilepticus (fNCSE) is a neurological condition characterized by a prolonged seizure that may lead to the development of epilepsy. Emerging experimental evidence implicates neuronal death, microglial activation and alterations in the excitatory and inhibitory synaptic balance as key features in the pathophysiology following fNCSE. We have previously reported alterations in the excitatory adhesion molecule N-cadherin in rats with fNCSE originating from the hippocampus that subsequently also develop spontaneous seizures. In this study, fNCSE rats were treated intraperitoneally with the conventional anti-epileptic drug levetiracetam in combination with intraparenchymal infusion of N-cadherin antibodies (Ab) for 4 weeks post-fNCSE. The N-cadherin Ab was infused into the fornix and immunohistochemically N-cadherin Ab-stained neurons were detected within the dorsal hippocampal structures as well as in superjacent somatosensory cortex. Continuous levetiracetam treatment for 4 weeks post-fNCSE reduced microglia activation, including cell numbers and morphological changes, partly decreased neuronal cell loss, and excitatory post-synaptic scaffold protein PSD-95 expression in selective hippocampal structures. The additional treatment with N-cadherin Ab did not reverse neuronal loss, but moderately reduced microglial activation, and further reduced PSD-95 levels in the dentate hilus of the hippocampus. Despite the effects on brain pathology within the epileptic focus, neither monotherapy with systemic levetiracetam nor levetiracetam in combination with local N-cadherin Ab administration, reduced the amount of focal or focal evolving into bilateral convulsive seizures, seizure duration, or interictal epileptiform activity during 1 month of continuous electroenephalogram recordings within the hippocampus after fNCSE. Behavioral tests for spatial memory, anxiety, social interaction and anhedonia did not detect gross behavioral differences between fNCSE rats with or without treatment. The results reveal the refractory features of the present rodent model of temporal lobe epilepsy following fNCSE, which supports its clinical value for further therapeutic studies. We identify the persistent development of epilepsy following fNCSE, in spite of partly reduced brain pathology within the epileptic focus.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

scholarly journals Sleep slow-wave homeostasis and cognitive functioning in children with electrical status epilepticus in sleep

SLEEP ◽  
2020 ◽  
Vol 43 (11) ◽  
Author(s):  
Bart van den Munckhof ◽  
Silvano R Gefferie ◽  
Suus A M van Noort ◽  
Heleen C van Teeseling ◽  
Mischa P Schijvens ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Slow Wave ◽  
Behavioral Problems ◽  
Rem Sleep ◽  
Epileptiform Activity ◽  
Slow Waves ◽  
Epileptic Focus ◽  
Test Results ◽  
Cross Sectional ◽  
Synaptic Homeostasis

Abstract Study Objectives Encephalopathy with electrical status epilepticus in sleep (ESES) is characterized by non-rapid eye movement (non-REM)-sleep-induced epileptiform activity and acquired cognitive deficits. The synaptic homeostasis hypothesis describes the process of daytime synaptic potentiation balanced by synaptic downscaling in non-REM-sleep and is considered crucial to retain an efficient cortical network. We aimed to study the overnight decline of slow waves, an indirect marker of synaptic downscaling, in patients with ESES and explore whether altered downscaling relates to neurodevelopmental and behavioral problems. Methods Retrospective study of patients with ESES with at least one whole-night electroencephalogram (EEG) and neuropsychological assessment (NPA) within 4 months. Slow waves in the first and last hour of non-REM-sleep were analyzed. Differences in slow-wave slope (SWS) and overnight slope course between the epileptic focus and non-focus electrodes and relations to neurodevelopment and behavior were analyzed. Results A total of 29 patients with 44 EEG ~ NPA combinations were included. Mean SWS decreased from 357 to 327 µV/s (−8%, p < 0.001) across the night and the overnight decrease was less pronounced in epileptic focus than in non-focus electrodes (−5.6% vs. −8.7%, p = 0.003). We found no relation between SWS and neurodevelopmental test results in cross-sectional and longitudinal analyses. Patients with behavioral problems showed less SWS decline than patients without and the difference was most striking in the epileptic focus (−0.9% vs. −8.8%, p = 0.006). Conclusions Slow-wave homeostasis—a marker of synaptic homeostasis—is disturbed by epileptiform activity in ESES. Behavioral problems, but not neurodevelopmental test results, were related to severity of this disturbance.

scholarly journals Non-convulsive status epilepticus diagnostics in severe brain injury: dynamics of clinical-electroencephalographic criteria

2020 ◽  
Vol 4 (36) ◽  
pp. 8-14
Author(s):  
M. V. Aleksandrov ◽  
E. S. Povalyukhina ◽  
T. V. Alexandrova ◽  
A. Yu. Ulitin
Keyword(s):  
Status Epilepticus ◽  
Brain Injury ◽  
Diagnostic Criteria ◽  
Activity Index ◽  
Epileptiform Activity ◽  
Spontaneous Respiration ◽  
Convulsive Status Epilepticus ◽  
Severe Brain Injury ◽  
The Unconscious ◽  
Unconscious State

Non-convulsive status epilepticus (NCSE) in case of severe traumatic brain injury is the reason for the persistence of a long unconscious state in the postcomatose period. Currently, there are no unified EEG-criteria for the diagnosis of non-convulsive status epilepticus. The proposed diagnostic criteria do not provide the neurodynamics of the damaged brain. The results, obtained in this work, allow us to clarify the relationship between the duration of the postcomatose period and the severity of pathological changes on the EEG. Diagnostic criteria for NCSE are proposed for the different periods of the acute period of traumatic brain damage. In the first 3–5 days of a postcomatose unconscious state, NCSE is diagnosed with an epileptiform activity index of at least 50 %. When the unconscious state lasts more than 7–10 days, the registration of epileptiform activity with an index of more than 25–30 % is a sufficient criterion for the diagnosis of NCSE. It has been shown that the formation of non-convulsive epileptic status can occur “delayed”, after more than 10–14 days from the moment of restoration of spontaneous respiration, which necessitates EEG monitoring throughout the entire period of the unconscious state in patients with severe brain injury.

Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism

2021 ◽  
pp. 096032712110134
Author(s):  
S Rahi ◽  
R Gupta ◽  
A Sharma ◽  
S Mehan
Keyword(s):  
Propionic Acid ◽  
Developmental Process ◽  
Morphological Changes ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Autism Spectrum ◽  
Neurodevelopmental Disease ◽  
Shh Pathway ◽  
Apoptotic Markers ◽  
The Impact

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disease characterized by cognitive and sensorimotor impairment. Numerous research findings have consistently shown that alteration of Smo-Shh (smoothened-sonic hedgehog) signaling during the developmental process plays a significant role in ASD and triggers neuronal changes by promoting neuroinflammation and apoptotic markers. Purmorphamine (PUR), a small purine-derived agonist of the Smo-Shh pathway, shows resistance to hippocampal neuronal cell oxidation and decreases neuronal cell death. The goal of this study was to investigate the neuroprotective potential of PUR in brain intoxication induced by intracerebroventricular-propionic acid (ICV-PPA) in rats, with a focus on its effect on Smo-Shh regulation in the brain of rats. In addition, we analyze the impact of PUR on myelin basic protein (MBP) and apoptotic markers such as Caspase-3, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic) in rat brain homogenates. Chronic ICV-PPA infusion was administered consecutively for 11 days to induce autism in rats. In order to investigate behavioral alterations, rats were tested for spatial learning in the Morris Water Maze (MWM), locomotive alterations using actophotometer, and beam crossing task, while Forced Swimming Test (FST) for depressive behavior. PUR treatment with 5 mg/kg and 10 mg/kg (i.p.) was administered from day 12 to 44. Besides cellular, molecular and neuroinflammatory analyses, neurotransmitter levels and oxidative markers have also been studied in brain homogenates. The results of this study have shown that PUR increases the level of Smo-Shh and restores the neurochemical levels, and potentially prevents morphological changes, including demyelination.

scholarly journals Emergency management of the paediatric patient with convulsive status epilepticus

2021 ◽  
Vol 26 (1) ◽  
pp. 50-57
Author(s):  
Kyle C McKenzie ◽  
Cecil D Hahn ◽  
Jeremy N Friedman
Keyword(s):  
Clinical Practice ◽  
Status Epilepticus ◽  
Emergency Management ◽  
Treatment Algorithm ◽  
Position Statement ◽  
Convulsive Status Epilepticus ◽  
Pharmacological Management ◽  
The Past ◽  
New Treatment ◽  
New Evidence

Abstract This guideline addresses the emergency management of convulsive status epilepticus (CSE) in children and infants older than 1 month of age. It replaces a previous position statement from 2011, and includes a new treatment algorithm and table of recommended medications based on new evidence and reflecting the evolution of clinical practice over the past several years. This statement emphasizes the importance of timely pharmacological management of CSE, and includes some guidance for diagnostic approach and supportive care.

scholarly journals Impact of Gba2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Etsuro Nakanishi ◽  
Norihito Uemura ◽  
Hisako Akiyama ◽  
Masato Kinoshita ◽  
Sawamura Masanori ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Biochemical Analysis ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Pathological Changes ◽  
Gaucher's Disease ◽  
Gaucher’S Disease ◽  
Short Lifespan ◽  
Behavioral Abnormalities ◽  
Glucocerebrosidase Gene

AbstractHomozygous mutations in the lysosomal glucocerebrosidase gene, GBA1, cause Gaucher’s disease (GD), while heterozygous mutations in GBA1 are a strong risk factor for Parkinson’s disease (PD), whose pathological hallmark is intraneuronal α-synuclein (asyn) aggregates. We previously reported that gba1 knockout (KO) medaka exhibited glucosylceramide accumulation and neuronopathic GD phenotypes, including short lifespan, the dopaminergic and noradrenergic neuronal cell loss, microglial activation, and swimming abnormality, with asyn accumulation in the brains. A recent study reported that deletion of GBA2, non-lysosomal glucocerebrosidase, in a non-neuronopathic GD mouse model rescued its phenotypes. In the present study, we generated gba2 KO medaka and examined the effect of Gba2 deletion on the phenotypes of gba1 KO medaka. The Gba2 deletion in gba1 KO medaka resulted in the exacerbation of glucosylceramide accumulation and no improvement in neuronopathic GD pathological changes, asyn accumulation, or swimming abnormalities. Meanwhile, though gba2 KO medaka did not show any apparent phenotypes, biochemical analysis revealed asyn accumulation in the brains. gba2 KO medaka showed a trend towards an increase in sphingolipids in the brains, which is one of the possible causes of asyn accumulation. In conclusion, this study demonstrated that the deletion of Gba2 does not rescue the pathological changes or behavioral abnormalities of gba1 KO medaka, and GBA2 represents a novel factor affecting asyn accumulation in the brains.

Salzburg Criteria, A Useful Tool in Non-Convulsive Status Epilepticus Diagnosis: A Retrospective Study

2021 ◽  
pp. 155005942199171
Author(s):  
Adriana Gómez Domínguez ◽  
Raidili C. Mateo Montero ◽  
Alba Díaz Cid ◽  
Antonio J. P. Mazarro ◽  
Ignacio R. Bailly-Bailliere ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Status Epilepticus ◽  
Prospective Studies ◽  
Correct Diagnosis ◽  
Original Description ◽  
Neurological Deficits ◽  
Convulsive Status Epilepticus ◽  
Poor Outcome

Introduction. Non-convulsive status epilepticus (NCSE) has been traditionally a challenging electroencephalographic (EEG) diagnosis. For this reason, Salzburg consensus criteria (SCC) have been proposed to facilitate correct diagnosis. Methods. We retrospectively reanalyzed 41 cases referred to our department (from 2016 to 2018) under the suspicion of NCSE. In this study, we compared the original description (standard criteria) versus the updated description (SCC) of the same EEG. Results. Originally, 15 patients were diagnosed as NCSE (37%) and 26 patients as no NCSE (63%), using the standard criteria. Then, we analyzed EEGs according to the SCC, which led to the following results: 9 patients fulfilled the criteria for definite NCSE (22%), 20 patients were diagnosed as possible NCSE (49%) and 12 patients were diagnosed as no NCSE (29%). Subsequently, when we analyze the outcome of possible NCSE cases, we note that 50% of these patients presented mild-poor outcome (neurological deficits, deceased). Indeed, we observed worse outcomes in patients previously diagnosed as no NCSE and untreated, specifically post-anoxic cases. Conclusions. Salzburg criteria seem to be a useful tool to support NCSE diagnosis, introducing the category of possible NCSE. In our study, we observed that it contributes to improving the prognosis and management of the patients. However, more prospective studies are needed to demonstrate the accuracy of SCC.

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