scholarly journals Effects of Three Anti-Seizure Drugs on Cholinergic and Metabolic Activity in Experimental Status Epilepticus

2019 ◽  
Vol 22 ◽  
pp. 340-351 ◽  
Author(s):  
Imran Imran ◽  
Konrad Koch ◽  
Henrik Schöfer ◽  
Helene Lau ◽  
Jochen Klein
Keyword(s):  
Oxidative Stress ◽  
Valproic Acid ◽  
Status Epilepticus ◽  
Metabolic Activity ◽  
Seizure Activity ◽  
In Vivo Microdialysis ◽  
Ach Release ◽  
Recurrent Seizure ◽  
Pilocarpine Model

Purpose. Status epilepticus (SE) is characterized by recurrent seizure activity and can be drug-resistant. Knowledge of neuronal and metabolic activity of the brain during SE may be helpful to improve medical care. We here report the effects of three anti-seizure drugs on changes of acetylcholine energy metabolites and oxidative stress during SE. Methods. We used the lithium-pilocarpine model in rats to induce SE and in vivo-microdialysis to monitor cholinergic and metabolic activity in the hippocampus. We measured extracellular concentrations of acetylcholine, glucose, lactate, pyruvate, glycerol and isoprostanes before and during SE, and after acute treatment with pregabalin, valproic acid, and levetiracteam. Results. Upon onset of  SE, acetylcholine (ACh) release increased six- to eightfold. Glucose was increased only transiently by 30% but lactate levels rose four-fold, and extracellular concentrations of glycerol ten-fold. Isoprostanes are markers of oxidative stress and increased more than 20-fold. Two hours after pilocarpine adminstration, rats were treated with pregabalin (100 mg/kg), levetiracetam (200 mg/kg) or valproic acid (400 mg/kg) by i.p. injection. All three drugs stopped seizure activity in a delayed fashion, but at the doses indicated, only animals that received levetiracetam reached consciousness. All drugs reduced ACh release within 60-120 minutes. Lactate/pyruvate ratios, glycerol and isoprostanne levels were also reduced significantly after drug administration. Conclusions. Hippocampal ACh release closely follows seizure activity in SE and is attenuated when SE subsides. Pregabalin, valproic acid and levetiracetam all terminate seizures in the rat SE model and attenuate cholinergic and metabolic changes within two hours.

scholarly journals Sudden altered mental state in the elderly: nonconvulsive status epilepticus and the role of the Emergency Department

2011 ◽  
Vol 5 (1) ◽  
pp. 15-25
Author(s):  
Rocco Galimi
Keyword(s):  
Status Epilepticus ◽  
Seizure Activity ◽  
The Elderly ◽  
Altered Mental Status ◽  
Nonconvulsive Status Epilepticus ◽  
Recurrent Seizure ◽  
Memory Problems ◽  
Altered Mental State ◽  
New Onset

In the elderly, new onset of epilepsy is often associated with vague complaints such as confusion, altered mental status, or memory problems. The absence of clinically apparent convulsions in association with an electroencephalogram showing continuous or recurrent seizure activity has been called nonconvulsive status epilepticus (NCSE). The purpose of this article is to describe the clinical and electroencephalographic features of NCSE in older adults. NCSE is an important, under-recognised and reversible cause of acute prolonged confusion. Although attempts have been made to define and classify this disorder, there is no universally accepted definition or classification yet that encompasses all subtypes or electroclinical scenarios. A urgent electroencephalogram is considered as the method of choice in the diagnostic evaluation of NCSE. Further researches are needed to better define NCSE.

Pedunculopontine stimulation alters respiration and increases ACh release in the pontine reticular formation

1993 ◽  
Vol 264 (3) ◽  
pp. R544-R554 ◽  
Author(s):  
R. Lydic ◽  
H. A. Baghdoyan
Keyword(s):  
Respiratory Rate ◽  
Respiratory Depression ◽  
Reticular Formation ◽  
Time Course ◽  
Cholinergic Neurons ◽  
In Vivo Microdialysis ◽  
Pedunculopontine Tegmental Nucleus ◽  
Pontine Reticular Formation ◽  
Ach Release

The present study examined the hypothesis that cholinergic neurons in the pedunculopontine tegmental nucleus (PPT) can cause the release of acetylcholine (ACh) in the pontine reticular formation and contribute to respiratory depression. In vivo microdialysis of the gigantocellular tegmental field (FTG) was performed in 10 adult male cats while respiration was being measured. In four intact, unanesthetized cats these measurements were obtained during states of quiet wakefulness and during the rapid eye movement (REM) sleeplike state caused by FTG microinjections of carbachol. The results demonstrate a simultaneous time course of enhanced ACh release in the FTG and respiratory rate depression. In six barbiturate-anesthetized cats similar measurements were obtained while PPT regions containing NADPH-positive neurons were electrically stimulated. PPT stimulation caused increased ACh release in the FTG and caused respiratory rate depression. Together, these findings are consistent with the hypothesis of a causal relationship between ACh release in the FTG and respiratory depression.

GABAA Receptors Inhibit Acetylcholine Release in Cat Pontine Reticular Formation: Implications for REM Sleep Regulation

2004 ◽  
Vol 92 (4) ◽  
pp. 2198-2206 ◽  
Author(s):  
Jacqueline Vazquez ◽  
Helen A. Baghdoyan
Keyword(s):  
Reticular Formation ◽  
Rem Sleep ◽  
In Vivo Microdialysis ◽  
Pontine Reticular Formation ◽  
Gamma Aminobutyric Acid ◽  
Ach Release ◽  
Sleep Regulation ◽  
Maximal Increase ◽  
Series Of Experiments

This study used in vivo microdialysis in cat ( n = 12) to test the hypothesis that gamma aminobutyric acid A (GABAA) receptors in the pontine reticular formation (PRF) inhibit acetylcholine (ACh) release. Animals were anesthetized with halothane to hold arousal state constant. Six concentrations of the GABAA receptor antagonist bicuculline (0.03, 0.1, 0.3, 1, 3, and 10 mM) were delivered to a dialysis probe in the PRF, and endogenously released ACh was collected simultaneously. Bicuculline caused a concentration dependent increase in ACh release (maximal increase = 345%; EC50 = 1.3 mM; r2 = 0.997). Co-administration of the GABAA receptor agonist muscimol prevented the bicuculline-induced increase in ACh release. In a second series of experiments, the effects of bicuculline (0.1, 0.3, 1, and 3 mM) on ACh release were examined without the use of general anesthesia. States of wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep were identified polygraphically before and during dialysis delivery of bicuculline. Higher concentrations of bicuculline (1 and 3 mM) significantly increased ACh release during wakefulness (36%), completely suppressed non-REM sleep, and increased ACh release during REM sleep (143%). The finding that ACh release in the PRF is modulated by GABAA receptors is consistent with the interpretation that inhibition of GABAergic transmission in the PRF contributes to the generation of REM sleep, in part, by increasing pontine ACh release.

scholarly journals The Impact of the Combined Administration of 1MeTIQ and MK-801 on Cell Viability, Oxidative Stress Markers, and Glutamate Release in the Rat Hippocampus

2021 ◽  
Author(s):  
Agnieszka Wąsik ◽  
Magdalena Białoń ◽  
Danuta Jantas ◽  
Marcelina Żarnowska
Keyword(s):  
Oxidative Stress ◽  
Enzyme Activity ◽  
Antioxidant Enzyme ◽  
Glutamate Release ◽  
Combined Treatment ◽  
In Vivo Microdialysis ◽  
Antioxidant Enzyme Activity ◽  
Rat Hippocampus ◽  
Mk 801

AbstractMK-801, as an N-methyl-D-aspartate (NMDA) receptor inhibitor, causes elevation in glutamate release, which may lead to an increase in excitotoxicity, oxidative stress and, consequently, cell death. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) shows antioxidant activity. The aim of the present study was to evaluate the effect of combined treatment with 1MeTIQ and MK-801 on cell viability, antioxidant enzyme activity, and glutamate release in the rat hippocampus. Cytotoxicity was measured using lactate dehydrogenase leakage assay (LDH) and the methyl tetrazolium (MTT) assay; antioxidant enzyme activity (glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)) were measured by ELISA kits. The release of glutamate in the rat hippocampus was measured using in vivo microdialysis methodology. An in vitro study showed that MK-801 induced cell death in a concentration-dependent manner and that 1MeTIQ partially reduced this adverse effect of MK-801. An ex vivo study indicated that MK-801 produced an increase in antioxidant enzyme activity (GPx, GR, and SOD), whereas coadministration of MK-801 and 1MeTIQ restored the activity of these enzymes to the control level. An in vivo microdialysis study demonstrated that combined treatment with both drugs decreased the release of glutamate in the rat hippocampus. The above results revealed that 1MeTIQ shows limited neuroprotective activity under conditions of glutamate-induced neurotoxicity.

Generalized convulsive status epilepticus after retrograde type A aortic dissection surgery

Perfusion ◽  
2020 ◽  
pp. 026765912094315
Author(s):  
Yuan Li ◽  
Qingchen Wu ◽  
Haoming Shi ◽  
Dan Chen ◽  
Cheng Zhang
Keyword(s):  
Status Epilepticus ◽  
Aortic Dissection ◽  
Seizure Activity ◽  
Good Condition ◽  
Type A ◽  
Convulsive Status Epilepticus ◽  
Recurrent Seizure ◽  
Type A Aortic Dissection ◽  
Generalized Seizures ◽  
First Time

Introduction: Generalized convulsive status epilepticus is defined as a generalized and convulsive seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures. For the first time, we present a case with retrograde type A aortic dissection after endovascular repairment and received thoracotomy intensely. Case report: The patient experienced frequent generalized seizures in the immediate postoperative period, and status epilepticus was considered for his medical history, clinic symptoms and related examinations. Discussion and Conclusion: Generalized convulsive status epilepticus should be alert for avoiding delay in the rehabilitation particularly after aortic dissection surgery. Under the good condition of ventilation, combining morphine with midazolam or diazepam can more effectively relieve the symptoms.

Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking

2001 ◽  
Vol 280 (2) ◽  
pp. R598-R601 ◽  
Author(s):  
Jacqueline Vazquez ◽  
Helen A. Baghdoyan
Keyword(s):  
Cognitive Deficits ◽  
Rem Sleep ◽  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Nrem Sleep ◽  
In Vivo Microdialysis ◽  
Ach Release ◽  
Behavioral Arousal ◽  
Function Of Sleep

Cholinergic neurons of the basal forebrain supply the neocortex with ACh and play a major role in regulating behavioral arousal and cortical electroencephalographic activation. Cortical ACh release is greatest during waking and rapid eye movement (REM) sleep and reduced during non-REM (NREM) sleep. Loss of basal forebrain cholinergic neurons contributes to sleep disruption and to the cognitive deficits of many neurological disorders. ACh release within the basal forebrain previously has not been quantified during sleep. This study used in vivo microdialysis to test the hypothesis that basal forebrain ACh release varies as a function of sleep and waking. Cats were trained to sleep in a head-stable position, and dialysis samples were collected during polygraphically defined states of waking, NREM sleep, and REM sleep. Results from 22 experiments in four animals demonstrated that means ± SE ACh release (pmol/10 min) was greatest during REM sleep (0.77 ± 0.07), intermediate during waking (0.58 ± 0.03), and lowest during NREM sleep (0.34 ± 0.01). The finding that, during REM sleep, basal forebrain ACh release is significantly elevated over waking levels suggests a differential role for basal forebrain ACh during REM sleep and waking.

scholarly journals Status Epilepticus Management: A Short Review

2016 ◽  
Vol 8 (2) ◽  
Author(s):  
Martin Savard MD
Keyword(s):  
Status Epilepticus ◽  
Seizure Activity ◽  
Short Review ◽  
High Morbidity ◽  
First Line ◽  
Recurrent Seizure ◽  
Electrographic Seizure ◽  
History Of ◽  
Medical Teams ◽  
Based Medicine

Status epilepticus is a common neurological emergency, with high morbidity and mortality, now defined as 5 minutes or more of (1) continuous clinical and/or electrographic seizure activity or (2) recurrent seizure activity without recovery (returning to baseline) between seizures. In observational studies, many disparities exist in management among different medical teams. Here, the author reviews evidence-based medicine data on this management, with emphasis on the use of drugs and electroencephalography. Benzodiazepine (either IV lorazepam or IM midazolam) are the recognized first line of treatment. When a patient is still seizing thereafter, the second line is usually either IV phenytoin or IV valproate, where available. A persisting status epilepticus should then be considered as refractory and managed with anaesthetic drug, keeping in mind that the natural history of that state is to evolve to nonconvulsive status epilepticus, where an emergent EEG is the only way to diagnose that condition with certainty.

scholarly journals Addressed delivery of valproic acid to target cells in treatment of epilepsy using aptamers

2021 ◽  
pp. 108-112
Author(s):  
T.N. Zamay ◽  
◽  
D.V. Dmitrenko ◽  
N.A. Shnaider ◽  
E.A. Narodova ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Status Epilepticus ◽  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Brain Barrier ◽  
Target Cells ◽  
Treatment Of Epilepsy ◽  
Blood Brain ◽  
Pilocarpine Model ◽  
The Brain

The aim of the research. To develop a drug based on aptamers that cross the blood-brain barrier, targeting the delivery of valproic acid to the brain. Material and methods. We used the Brain 1 and Co 451 aptamers passing through the blood-brain barrier, obtained using the in vivo-SELEX technology, the affi nity of which was determined using fl ow cytometry fl uorescence microscopy. Th e drug for targeted delivery of valproic acid was obtained using the conjugation of Konvulex, biotinylated aptamers, and streptavidin protein. Th e antiepileptic effi cacy of the drug was evaluated in ICR mice with a lithium-pilocarpine model of the development of epilepsy. Aft er the injection of pilocarpine, the animals were monitored using round-the-clock video recording. For the treatment of epilepsy, a valproic acid dose of 130 μg / g of animal weight was used. During treatment with a drug for targeted delivery, the dose of valproic acid was reduced to 5 μg / g. Evaluation of status epilepticus in mice was performed using the Racine Scale. Results. In animals, using the lithium-pilocarpine model, status epilepticus was formed at diff erent stages - from the 1st to the 5th. In all groups of animals, complete overcoming of status epilepticus did not occur in 120 min. In the group of mice treated with valroic acid, no change in their status occurred within 80 minutes. When mice were treated with conjugates based on the Brain 1 and Co 451 aptamers, the blockade of status epilepticus in mice, despite the lower (26 times) doses of the administered antiepileptic drug, occurred faster. Conclusion. A scientifi c platform has been developed for the development of drugs for targeted delivery of antiepileptic drugs with high effi ciency and low toxicity

scholarly journals CLINICAL PROFILE AND OUTCOME OF CHILDREN ADMITTED WITH STATUS EPILEPTICS

2021 ◽  
Vol 5 (9) ◽  
Author(s):  
Sushil Kuamr Bakolia ◽  
Gajendra Kumar Verma ◽  
Dinesh Kumar Barolia
Keyword(s):  
Status Epilepticus ◽  
Seizure Activity ◽  
Cross Sectional Study ◽  
Clonic Seizure ◽  
Clinical Profile ◽  
Convulsive Status Epilepticus ◽  
Age Group ◽  
Cross Sectional ◽  
Recurrent Seizure ◽  
Appropriate Treatment

Background: Objective of this study was to study epidemiology and clinical profile of Status epilepticus Methods: Hospital based cross sectional study conducted on 50 children All children aged between 1 month to 12 years who at presentation or during the PICU stay had convulsive status epilepticus - defined as continuous seizure activity or recurrent seizure activity without regaining consciousness lasting for >5 min. Results: Among 50 children 56.00 % were in the age group were less than 5 years ,24 % were between 6-10 years ,20.00 % were above 10 yrs. The mean age group was 6.21±1.26 years. Incidence was higher in males (64%) when compared to females (36%). Generalized tonic clonic seizure were observed in 46 (92.00%) and partial seizure was noted in 4 (8%) of the children. About 36 (72%) of the children developed SE for the first time. Conclusion: Status epilepticus is one of the common neurological emergency which requires admission to PICU. In our study epilepsy is one of the most common causes of status epilepticus. Early and appropriate treatment with anticonvulsants and use of mechanical ventilation may improve the outcome. Keywords: Status epilepticus, mortality, clinical profile

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