Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat.

Science.gov (United States)

Foote, F; Gale, K

1983-11-25

In a naloxone-reversible, dose-dependent manner, morphine (10-50 mg/kg i.p.) protected against seizures induced by maximal electroshock and increased the incidence and severity of seizures induced by bicuculline, in rats. Morphine also potentiated seizures induced by isoniazid and by picrotoxin. Thus, opiate activity influences the expression of seizures in contrasting ways depending upon the mode of seizure induction. Since morphine consistently potentiated seizures induced by interference with GABA transmission, it appears that GABAergic systems may be of particular significance for the elucidation of the varied effects of morphine on seizure susceptibility.

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

Energy Technology Data Exchange (ETDEWEB)

Miller, Steven L., E-mail: stevenmiller17@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Aroniadou-Anderjaska, Vassiliki, E-mail: vanderjaska@usuhs.edu [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Figueiredo, Taiza H., E-mail: taiza.figueiredo.ctr@usuhs.edu [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Prager, Eric M., E-mail: eric.prager683@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Almeida-Suhett, Camila P., E-mail: camilapalmeida@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Apland, James P., E-mail: james.p.apland.civ@mail.mil [Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010 (United States); and others

2015-04-15

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD{sub 50} of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2 × LD{sub 50}), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. - Highlights: • The LD{sub 50} of soman was determined in postnatal-day-21 rats. • Rats with no seizures after 1.2XLD{sub 50} soman had less reduction of AChE in the amygdala. • Atropine sulfate (ATS) at 2 mg/kg, given at 20 min after

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

International Nuclear Information System (INIS)

Miller, Steven L.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Prager, Eric M.; Almeida-Suhett, Camila P.; Apland, James P.

2015-01-01

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD 50 of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2 × LD 50 ), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. - Highlights: • The LD 50 of soman was determined in postnatal-day-21 rats. • Rats with no seizures after 1.2XLD 50 soman had less reduction of AChE in the amygdala. • Atropine sulfate (ATS) at 2 mg/kg, given at 20 min after soman, blocked

An Important Chemical Weapon Group: Nerve Agents

Directory of Open Access Journals (Sweden)

Hakan Yaren

2007-12-01

Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull 2007; 6(6.000: 491-500

An Important Chemical Weapon Group: Nerve Agents

Directory of Open Access Journals (Sweden)

Hakan Yaren

2007-12-01

Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull. 2007; 6(6: 491-500

LABORATORY EXAMINATION IN NERVE AGENT INTOXICATION

Directory of Open Access Journals (Sweden)

Jiří Bajgar

2013-01-01

Full Text Available Diagnosis of nerve agent intoxication is based on anamnestic data, clinical signs and laboratory examination. For acute poisoning, cholinesterase activity in the blood (erythrocyte AChE, plasma/serum BuChE is sensitive, simple and most frequent laboratory examination performed in biochemical laboratories. Specialized examinations to precise treatment (reactivation test or to make retrospective diagnosis (fluoride induced reactivation etc. can be conducted. Other sophisticated methods are available, too.

REM sleep pathways and anticholinesterase intoxication: A mechanism for nerve agent-induced, central respiratory failure.

NARCIS (Netherlands)

Kok, A.

1993-01-01

The mechanism of death following exposure to anticholinesterases, such as the highly toxic nerve agents soman and VX, and other organophosphate anticholinesterases such as the insecticide parathion, remains unclear, although evidence from nerve agent research suggests that death occurs by an

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

OpenAIRE

RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

2014-01-01

Background Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic ef...

Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage

Energy Technology Data Exchange (ETDEWEB)

Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio [Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612 (United States); Auta, James [Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612 (United States)

2009-02-27

Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at {alpha}1- but is a high efficacy positive allosteric modulator at {alpha}5-containing GABA{sub A} receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5

Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage

International Nuclear Information System (INIS)

Kadriu, Bashkim; Guidotti, Alessandro; Costa, Erminio; Auta, James

2009-01-01

Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at α1- but is a high efficacy positive allosteric modulator at α5-containing GABA A receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or a

31 CFR 401.1 - Secret Service agents authorized to make seizures.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Secret Service agents authorized to... Finance (Continued) SECRET SERVICE, DEPARTMENT OF THE TREASURY SEIZURE AND FORFEITURE OF VESSELS, VEHICLES... Secret Service agents authorized to make seizures. All officers of the U.S. Secret Service engaged in the...

Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

Science.gov (United States)

Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

2017-09-01

Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists.

Science.gov (United States)

Miller, Steven L; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Prager, Eric M; Almeida-Suhett, Camila P; Apland, James P; Braga, Maria F M

2015-04-15

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2mg/kg, administered 20 min after soman exposure (1.2×LD50), terminated seizures. ATS at 0.5mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1h post-exposure, prevents brain pathology and behavioral deficits. Published by Elsevier Inc.

Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

Science.gov (United States)

Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

2015-01-01

Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P seizure threshold (P seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

The effects of glycemic control on seizures and seizure-induced excitotoxic cell death

Directory of Open Access Journals (Sweden)

Schauwecker Paula

2012-08-01

Full Text Available Abstract Background Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide. Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. It is known that seizures result in altered glucose metabolism, the reduction of intracellular energy metabolites such as ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates, such as lactate and adenosine. In particular, it has been suggested that the duration and extent of glucose dysregulation may be a predictor of the pathological outcome of status. However, little is known about neither the effects of glycemic control on brain metabolism nor the effects of managing systemic glucose concentrations in epilepsy. Results In this study, we examined glycemic modulation of kainate-induced seizure sensitivity and its neuropathological consequences. To investigate the relationship between glycemic modulation, seizure susceptibility and its neuropathological consequences, C57BL/6 mice (excitotoxin cell death resistant were subjected to hypoglycemia or hyperglycemia, followed by systemic administration of kainic acid to induce seizures. Glycemic modulation resulted in minimal consequences with regard to seizure severity but increased hippocampal pathology, irrespective of whether mice were hypoglycemic or hyperglycemic prior to kainate administration. Moreover, we found that exogenous administration of glucose following kainic acid seizures significantly reduced the extent of hippocampal pathology in FVB/N mice (excitotoxin cell death susceptible following systemic administration of kainic acid. Conclusion These findings demonstrate that modulation of the glycemic index can modify the outcome of brain injury in the kainate model of seizure induction. Moreover, modulation of the glycemic index through glucose rescue greatly diminishes the extent of seizure-induced

Vagus nerve stimulation magnet activation for seizures: a critical review.

Science.gov (United States)

Fisher, R S; Eggleston, K S; Wright, C W

2015-01-01

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Behavioral effects of nerve agents: laboratory animal models

International Nuclear Information System (INIS)

Myers, T. M.

2009-01-01

Diverse and often subtle behavioral consequences have been reported for humans exposed to nerve agents. Laboratory studies of nerve agent exposure offer rigorous control over important variables, but species other than man must be used. Nonhuman primate models offer the best means of identifying the toxic nervous system effects of nerve agent insult and the countermeasures best capable of preventing or attenuating these effects. Comprehensive behavioral models must evaluate preservation and recovery of function as well as new learning ability. The throughput and sensitivity of the tests chosen are important considerations. A few nonhuman primate studies will be discussed to elaborate recent successes, current limitations, and future directions.(author)

The combination of donepezil and procyclidine protects against soman-induced seizures in rats

International Nuclear Information System (INIS)

Haug, Kristin Huse; Myhrer, Trond; Fonnum, Frode

2007-01-01

Current treatment of nerve agent poisoning consists of prophylactic administration of pyridostigmine and therapy using atropine, an oxime and a benzodiazepine. Pyridostigmine does however not readily penetrate the blood-brain barrier giving ineffective protection of Brain against centrally mediated seizure activity. In this study, we have evaluated donepezil hydrochloride, a partial reversible inhibitor of acetylcholinesterase (AChE) clinically used for treating Alzheimer's disease, in combination with procyclidine, used in treatment of Parkinson's disease and schizophrenia, as prophylaxis against intoxication by the nerve agent soman. The results demonstrated significant protective efficacy of donepezil (2.5 mg/kg) combined with procyclidine (3 or 6 mg/kg) when given prophylactically against a lethal dose of soman (1.6x LD 50 ) in Wistar rats. No neuropathological changes were found in rats treated with this combination 48 h after soman intoxication. Six hours after soman exposure cerebral AChE activity and acetylcholine (ACh) concentration was 5% and 188% of control, respectively. The ACh concentration had returned to basal levels 24 h after soman intoxication, while AChE activity had recovered to 20% of control. Loss of functioning muscarinic ACh receptors (17%) but not nicotinic receptors was evident at this time point. The recovery in brain AChE activity seen in our study may be due to the reversible binding of donepezil to the enzyme. Donepezil is well tolerated in humans, and a combination of donepezil and procyclidine may prove useful as an alternative to the currently used prophylaxis against nerve agent intoxication

Behaviors induced or disrupted by complex partial seizures.

Science.gov (United States)

Leung, L S; Ma, J; McLachlan, R S

2000-09-01

We reviewed the neural mechanisms underlying some postictal behaviors that are induced or disrupted by temporal lobe seizures in humans and animals. It is proposed that the psychomotor behaviors and automatisms induced by temporal lobe seizures are mediated by the nucleus accumbens. A non-convulsive hippocampal afterdischarge in rats induced an increase in locomotor activity, which was suppressed by the injection of dopamine D(2) receptor antagonist in the nucleus accumbens, and blocked by inactivation of the medial septum. In contrast, a convulsive hippocampal or amygdala seizure induced behavioral hypoactivity, perhaps by the spread of the seizure into the frontal cortex and opiate-mediated postictal depression. Mechanisms underlying postictal psychosis, memory disruption and other long-term behavioral alterations after temporal lobe seizures, are discussed. In conclusion, many of the changes of postictal behaviors observed after temporal lobe seizures in humans may be found in animals, and the basis of the behavioral change may be explained as a change in neural processing in the temporal lobe and the connecting subcortical structures.

Nerve agent intoxication: Recent neuropathophysiological findings and subsequent impact on medical management prospects

International Nuclear Information System (INIS)

Collombet, Jean-Marc

2011-01-01

This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3 months after soman poisoning. Indeed, an increased proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents. - Highlights: → This review focuses on neuropathophysiology following nerve agent poisoning in mice. → Extensive data on long-term neuropathology and related inflammation are provided here. → Delayed self-repair attempts encountered in lesioned rodent brains are also described. → Cell therapy is considered as a valuable treatment against nerve agent intoxication.

Oxaliplatin-Induced Tonic-Clonic Seizures

Directory of Open Access Journals (Sweden)

Ahmad K. Rahal

2015-01-01

Full Text Available Oxaliplatin is a common chemotherapy drug used for colon and gastric cancers. Common side effects are peripheral neuropathy, hematological toxicity, and allergic reactions. A rare side effect is seizures which are usually associated with posterior reversible leukoencephalopathy syndrome (PRES. A 50-year-old male patient presented with severe abdominal pain. CT scan of the abdomen showed acute appendicitis. Appendectomy was done and pathology showed mixed adenoneuroendocrine carcinoma. Adjuvant chemotherapy was started with Folinic acid, Fluorouracil, and Oxaliplatin (FOLFOX. During the third cycle of FOLFOX, the patient developed tonic-clonic seizures. Laboratory workup was within normal limits. EEG and MRI of the brain showed no acute abnormality. The patient was rechallenged with FOLFOX but he had tonic-clonic seizures for the second time. His chemotherapy regimen was switched to Folinic acid, Fluorouracil, and Irinotecan (FOLFIRI. After 5 cycles of FOLFIRI, the patient did not develop any seizures, making Oxaliplatin the most likely culprit for his seizures. Oxaliplatin-induced seizures rarely occur in the absence of PRES. One case report has been described in the literature. We present a rare case of tonic-clonic seizures in a patient receiving Oxaliplatin in the absence of PRES.

Organophosphate Nerve Agent Detection with Europium Complexes

Directory of Open Access Journals (Sweden)

Jake R. Schwierking

2004-01-01

Full Text Available We explore the detection of paraoxon, a model compound for nonvolatile organophosphate nerve agents such as VX. The detection utilizes europium complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing ligands. Both europium luminescence quenching and luminescence enhancement modalities are involved in the detection, which is simple, rapid, and sensitive. It is adaptable as well to the more volatile fluorophosphate nerve agents. It involves nothing more than visual luminescence observation under sample illumination by an ordinary hand-held ultraviolet lamp.

Seizures induced by carbachol, morphine, and leucine-enkephalin: a comparison.

Science.gov (United States)

Snead, O C

1983-04-01

The electrical, behavioral, and pharmacological properties of seizures induced by morphine, leucine-enkephalin, and the muscarinic cholinergic agonist carbachol were examined and compared. Low-dose carbachol given intracerebroventricularly (ICV) produced seizures similar electrically to those produced by ICV morphine and leucine-enkephalin, although there was some difference in site of subcortical origin of onset. Carbachol and morphine were similar in that they had the same anticonvulsant profile, produced similar behavioral changes, caused generalized absence seizures in low doses and generalized convulsive seizures in high doses, and were capable of chemical kindling. However, opiate-induced seizures were not overcome by cholinergic antagonists, nor were carbachol seizures blocked by opiate antagonists. These data suggest that there may be a common noncholinergic, nonopiatergic system involved in mediating carbachol- and morphine-induced seizures but not enkephalin seizures.

Metal organic frameworks for the catalytic detoxification of chemical warfare nerve agents

Science.gov (United States)

Hupp, Joseph T.; Farha, Omar K.; Katz, Michael J.; Mondloch, Joseph E.

2017-04-18

A method of using a metal organic framework (MOF) comprising a metal ion and an at least bidendate organic ligand to catalytically detoxify chemical warfare nerve agents including exposing the metal-organic-framework (MOF) to the chemical warfare nerve agent and catalytically decomposing the nerve agent with the MOF.

Modulation of Hippocampal Activity by Vagus Nerve Stimulation in Freely Moving Rats

NARCIS (Netherlands)

Larsen, L.E.; Wadman, W.J.; van Mierlo, P.; Delbeke, J.; Grimonprez, A.; Van Nieuwenhuyse, B.; Portelli, J.; Boon, P; Vonck, K.; Raedt, R.

2015-01-01

BACKGROUND: Vagus Nerve Stimulation (VNS) has seizure-suppressing effects but the underlying mechanism is not fully understood. To further elucidate the mechanisms underlying VNS-induced seizure suppression at a neurophysiological level, the present study examined effects of VNS on hippocampal

Disparity in regional cerebral blood flow during electrically induced seizure

DEFF Research Database (Denmark)

Sestoft, D; Meden, P; Hemmingsen, R

1993-01-01

This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized on electroencepha......This is a presentation of 2 cases in which the intraictal regional cerebral blood flow distribution was measured with the 99mTc-HMPAO single photon emission computerized tomography technique during an electrically induced seizure. Although the seizure was verified as generalized...... electroencephalography-verified generalized seizures....

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

Directory of Open Access Journals (Sweden)

Luciano Rezende Vilela

2015-01-01

Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

Improvements of the fluoride reactivation method for the verification of nerve agent exposure

NARCIS (Netherlands)

Degenhardt, C.E.A.M.; Pleijsier, K.; Schans, M.J. van der; Langenberg, J.P.; Preston, K.E.; Solano, M.I.; Maggio, V.L.; Barr, J.R.

2004-01-01

One of the most appropriate biomarkers for the verification of organophosphorus nerve agent exposure is the conjugate of the nerve agent to butyrylcholinesterase (BuChE). The phosphyl moiety of the nerve agent can be released from the BuChE enzyme by incubation with fluoride ions, after which the

Influence of vigilance state on physiological consequences of seizures and seizure-induced death in mice.

Science.gov (United States)

Hajek, Michael A; Buchanan, Gordon F

2016-05-01

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of 12 adult male mice were instrumented for EEG, EMG, and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared with those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities that can predict which individuals have higher risk for seizure-induced death.

Opiate-induced seizures: a study of mu and delta specific mechanisms.

Science.gov (United States)

Snead, O C

1986-08-01

Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.

In Vivo Microdialysis and Electroencephalographic Activity in Freely Moving Guinea Pigs Exposed to Organophosphorus Nerve Agents Sarin and VX: Analysis of Acetylcholine and Glutamate

Science.gov (United States)

2011-01-01

support the idea that there is a triphasic NT model for onset and progression of seizures and subsequent brain damage upon acute exposure to nerve agent...col- umn reactor (ACH-SPR Part No. 70-0640), and analytical cell (Model 5040) were all obtained from ESA Biosci- ences, Inc. (Chelmsford, MA...injection volume was 10 ll. To facilitate EC detection, a post-column reactor was utilized to convert ACh and Ch to hydrogen peroxide. The signal from

Prevalence and Complications of Drug-induced Seizures in Baharloo Hospital, Tehran, Iran

Directory of Open Access Journals (Sweden)

Behnam Behnoush

2012-05-01

Full Text Available Background: Seizure is a frequent and important finding in the field of clinical toxicology. Almost all poisons and drugs can produce seizure. We have evaluated frequency and complications of drug-induced seizure in present study. Methods: The present descriptive cross-sectional study was done on patients who were referred to Baharloo Hospital, Tehran, Iran, that had developed seizure before or after hospitalization following intoxication between 20 March 2010 and 20 March 2011. The exclusion criteria were a positive history of epilepsy, head trauma, or abnormal findings in EEG or brain CT scan. Results: Tramadol and tricyclic antidepressants were the most common causes of drug-induced seizure (31.5% and 14.7% of the cases, respectively. Overall, 6 patients (4.2% had developed persistent vegetative state in consequence of brain hypoxia, 16 patients (11.2% had died due to complications of seizure or the poisoning itself. Tramadol was the leading cause of drug-induced seizure and its morbidity and mortality. Tonic-colonic seizure was the most common type of drug-induced seizure. Seizure had occurred once in 58% of the patients, twice in 37.1% of the patients, and had been revolutionized to status epilepticus in 4.9% of them. Among the 7 patients who had developed status epilepticus, 3 cases had died. Conclusion: Appropriate measures for treatment of seizure and prevention of its complications should be taken when patients with drug poisoning are admitted into hospital, especially when the offending drug(s has a higher likelihood to induce seizure.

Zirconium Hydroxide-coated Nanofiber Mats for Nerve Agent Decontamination.

Science.gov (United States)

Kim, Sohee; Ying, Wu Bin; Jung, Hyunsook; Ryu, Sam Gon; Lee, Bumjae; Lee, Kyung Jin

2017-03-16

Diverse innovative fabrics with specific functionalities have been developed for requirements such as self-decontamination of chemical/biological pollutants and toxic nerve agents. In this work, Zr(OH) 4 -coated nylon-6,6 nanofiber mats were fabricated for the decontamination of nerve agents. Nylon-6,6 fabric was prepared via the electrospinning process, followed by coating with Zr(OH) 4 , which was obtained by the hydrolysis of Zr(OBu) 4 by a sol-gel reaction on nanofiber surfaces. The reaction conditions were optimized by varying the amounts of Zr(OBu) 4 ,the reaction time, and the temperature of the sol-gel reaction. The composite nanofibers show high decontamination efficiency against diisopropylfluorophosphate, which is a nerve agent analogue, due to its high nucleophilicity that aids in the catalysis of the hydrolysis of the phosphonate ester bonds. Composite nanofiber mats have a large potential and can be applied in specific fields such as military and medical markets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery

Directory of Open Access Journals (Sweden)

Summer L. Gibbs-Strauss

2011-03-01

Full Text Available Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,4‘-[(2-methoxy-1,4-phenylenedi-(1E-2,1-ethenediyl]bis-benzenamine (BMB and a newly synthesized, red-shifted derivative 4-[(1E-2-[4-[(1E-2-[4-aminophenyl]ethenyl]-3-methoxyphenyl]ethenyl]-benzonitrile (GE3082 were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drug-imaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE™ (Fluorescence-Assisted Resection and Exploration imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.

Death from seizures induced by chronic alcohol abuse--does it exist?

DEFF Research Database (Denmark)

Christoffersen, S

2007-01-01

aetiologies, but in police reports a person known to have seizures is most likely to be reported as suffering from epilepsy. It is a well-known fact that alcoholics have seizures either due to "alcohol-induced epilepsy" or due to withdrawal from drinking. It also seems to be generally accepted that alcoholics...... may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure. RESULTS......: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse....

Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication.

Science.gov (United States)

Dunn, Emily N; Ferrara-Bowens, Teresa M; Chachich, Mark E; Honnold, Cary L; Rothwell, Cristin C; Hoard-Fruchey, Heidi M; Lesyna, Catherine A; Johnson, Erik A; Cerasoli, Douglas M; McDonough, John H; Cadieux, C Linn

2018-06-07

Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34 000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research.

Naloxone-induced electrographic seizures in the primate.

Science.gov (United States)

Snyder, E W; Shearer, D E; Beck, E C; Dustmann, R E

1980-01-01

Electrographic seizure activity was recorded shortly following naxolone injections in artificially ventilated, methadone-treated stump-tailed macaques. Plasma-methadone concentrations prior to seizure activity were many times higher than those that have produced respiratory depression and death in nonventilated monkeys. The duration of seizure activity was clearly related to the dose of naloxone. Naloxone was without epileptogenic properties in animals that had not been pretreated with methadone. The results suggest that methadone and naloxone have additive epileptogenic properties when high blood levels of methadone are achieved in the artificially ventilated primate. Naloxone was devoid of antagonistic properties with respect to opiate-induced electroencephalographic spiking activity.

Serotonin neurones have anti-convulsant effects and reduce seizure-induced mortality

Science.gov (United States)

Buchanan, Gordon F; Murray, Nicholas M; Hajek, Michael A; Richerson, George B

2014-01-01

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Defects in central control of breathing are important contributors to the pathophysiology of SUDEP, and serotonin (5-HT) system dysfunction may be involved. Here we examined the effect of 5-HT neurone elimination or 5-HT reduction on seizure risk and seizure-induced mortality. Adult Lmx1bf/f/p mice, which lack >99% of 5-HT neurones in the CNS, and littermate controls (Lmx1bf/f) were subjected to acute seizure induction by maximal electroshock (MES) or pilocarpine, variably including electroencephalography, electrocardiography, plethysmography, mechanical ventilation or pharmacological therapy. Lmx1bf/f/p mice had a lower seizure threshold and increased seizure-induced mortality. Breathing ceased during most seizures without recovery, whereas cardiac activity persisted for up to 9 min before terminal arrest. The mortality rate of mice of both genotypes was reduced by mechanical ventilation during the seizure or 5-HT2A receptor agonist pretreatment. The selective serotonin reuptake inhibitor citalopram reduced mortality of Lmx1bf/f but not of Lmx1bf/f/p mice. In C57BL/6N mice, reduction of 5-HT synthesis with para-chlorophenylalanine increased MES-induced seizure severity but not mortality. We conclude that 5-HT neurones raise seizure threshold and decrease seizure-related mortality. Death ensued from respiratory failure, followed by terminal asystole. Given that SUDEP often occurs in association with generalised seizures, some mechanisms causing death in our model might be shared with those leading to SUDEP. This model may help determine the relationship between seizures, 5-HT system dysfunction, breathing and death, which may lead to novel ways to prevent SUDEP. PMID:25107926

Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation.

Science.gov (United States)

Chwiej, J; Patulska, A; Skoczen, A; Matusiak, K; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

2017-07-01

In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2). KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals. Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region. Copyright © 2017 Elsevier GmbH. All rights reserved.

Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds

Directory of Open Access Journals (Sweden)

Mengxuan Gao

2017-02-01

Full Text Available Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as “seizure-inducing” drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.

Characteristics of seizure-induced signal changes on MRI in patients with first seizures.

Science.gov (United States)

Kim, Si Eun; Lee, Byung In; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Park, Kang Min; Kim, Hyung Chan; Lee, Joonwon; Bae, Soo-Young; Lee, Dongah; Kim, Sung Eun

2017-05-01

The aim of this study was to investigate the predictive factors and identify the characteristics of the seizure-induced signal changes on MRI (SCM) in patients with first seizures. We conducted a retrospective study of patients with first seizures from March 2010 to August 2014. The inclusion criteria for this study were patients with 1) first seizures, and 2) MRI and EEG performed within 24h of the first seizures. The definition of SCM was hyper-intensities in the brain not applying to cerebral arterial territories. Multivariate logistic regression was performed with or without SCM as a dependent variable. Of 431 patients with seizures visiting the ER, 69 patients met the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently significant variable predicting the presence of SCM in patients with first seizures. In addition, the topography of SCM was as follows; i) ipsilateral hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11), iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus (1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI exhibited unilateral cortical hyperperfusion with ipsilateral thalamic involvement reflecting unrestricted vascular territories. There is an association between epileptiform discharges and SCM. Additionally, the involvement of the unilateral cortex and ipsilateral thalamus in SCM and its hyperperfusion state could be helpful in differentiating the consequences of epileptic seizures from other pathologies. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy.

Science.gov (United States)

Welch, William P; Sitwat, Bilal; Sogawa, Yoshimi

2018-06-01

To describe the response to vagus nerve stimulator (VNS) in otherwise neurotypical children with medically intractable primary generalized epilepsy. Retrospective chart review of patients who underwent vagus nerve stimulator surgery between January 2011 and December 2015. Eleven patients were identified. Median follow-up duration was 2.5 years (1.2-8.4 years). Prior to vagus nerve stimulator surgery, all patients had at least 1 seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11 (55%) reported fewer than 1 seizure per month. Three patients (27%) reported complications related to vagus nerve stimulator surgery, and no patients required device removal. In children with medically intractable primary generalized epilepsy, vagus nerve stimulator is well tolerated and appears to lead to improvement in seizure frequency. Improvement was not attributable to epilepsy classification, age at vagus nerve stimulator implantation, output current, duty cycle, or follow-up duration.

Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures.

Directory of Open Access Journals (Sweden)

Min Li

Full Text Available Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6-(3-methoxyl-4-hydroxybenzyl adenine riboside (B2 is a N(6-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP, pentylenetetrazol (PTZ, picrotoxin, kainite acid (KA, or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.

Stimulation of Central A1 Adenosine Receptors Suppresses Seizure and Neuropathology in a Soman Nerve Agent Seizure Rat Model

Science.gov (United States)

2014-05-22

implantation site, Nissl stained , and then analyzed by a trained pathologist to verify the accuracy of cannulae placement and evaluate toxicity. The second...transcardial perfusion and fixation, the brains were sectioned and stained with Nissl . A trained pathologist then analyzed the sections and verified that CPA...proto- col was used for assessing neuropathology in the subsequent soman seizure experiments. Those brains were serial sec- tioned at 5 mm, stained

Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. (Reannouncement with new availability information)

Energy Technology Data Exchange (ETDEWEB)

Capacio, B.R.; Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Gales, V.

1992-12-31

The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepan, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. AH compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (micrometer ol/kg) values and peak effect tunes were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepwn, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock MES and subcutaneous pentylenetetrazol (scMET)). I serve agents, anticonvulsants, diazepam, accelerating rotarod, motor performance.

Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

Science.gov (United States)

Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

2016-03-09

It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results

Photosensitivity and visually induced seizures: review

NARCIS (Netherlands)

Parra, J.; Kalitzin, S.; Lopes da Silva, F.H.

2005-01-01

PURPOSE OF REVIEW: Interest in visually induced seizures has increased in recent years as a result of the increasing number of precipitants in our modern environment. This review addresses new developments in this field with special attention given to the emergence of new diagnostic, therapeutic and

Nerve Agents: What They Are, How They Work, How to Counter Them.

Science.gov (United States)

Costanzi, Stefano; Machado, John-Hanson; Mitchell, Moriah

2018-05-16

Nerve agents are organophosphorus chemical warfare agents that exert their action through the irreversible inhibition of acetylcholinesterase, with a consequent overstimulation of cholinergic transmission followed by its shutdown. Beyond warfare, they have notoriously been employed in acts of terrorism as well as high profile assassinations. After a brief historical introduction on the development and deployment of nerve agents, this review provides a survey of their chemistry, the way they affect cholinergic transmission, the available treatment options, and the current directions for their improvement. As the review illustrates, despite their merits, the currently available treatment options present several shortcomings. Current research directions involve the search for improved antidotes, antagonists of the nicotinic receptors, small-molecule pretreatment options, as well as bioscavengers as macromolecular pretreatment options. These efforts are making good progress in many different directions and, hopefully, will lead to a lower target susceptibility, thus reducing the appeal of nerve agents as chemical weapons.

Evaluation of the Effect of Jobelyn® on Chemoconvulsants- Induced Seizure in Mice

Directory of Open Access Journals (Sweden)

Solomon Umukoro

2013-04-01

Full Text Available Introduction: Epilepsy is a common central nervous system (CNS disorder characterized by seizures resulting from episodic neuronal discharges. The incidence of toxicity and refractoriness has compromised the clinical efficacy of the drugs currently used for the treatment of convulsions. Thus, there is a need to search for new medicines from plant origin that are readily available and safer for the control of seizures. Jobelyn® (JB is a unique African polyherbal preparation used by the natives to treat seizures in children. This investigation was carried out to evaluate whether JB has anti-seizure property in mice. Methods: The animals received JB (5, 10 and 20 mg/kg, p.o 30 min before induction of convulsions with intraperitoneal (i.p. injection of picrotoxin (6 mg/kg, strychnine (2 mg/ kg and pentylenetetrazole (85 mg/kg respectively. Diazepam (2 mg/kg, p.o. was used as the reference drug. Anti-seizure activities were assessed based on the ability of test drugs to prevent convulsions, death or to delay the onset of seizures in mice. Results: JB (5, 10 and 20 mg/kg, p.o could only delay the onset of seizures induced by pentylenetetrazole (85 mg/kg, i.p. in mice. However, it did not offer any protection against seizure episodes, as it failed to prevent the animals, from exhibiting tonic-clonic convulsions caused by pentylenetetrazole (85 mg/kg, i.p., strychnine (2 mg/kg or picrotoxin (6 mg/kg, i.p.. On the other hand, diazepam (2 mg/kg, p.o., offered 100% protection against convulsive seizures, induced by pentylenetetrazole (85 mg/kg, i.p.. However, it failed to prevent seizures produced by strychnine (2 mg/kg, i.p. or picrotoxin (6 mg/kg, i.p.. Discussion: Our results suggest that JB could not prevent the examined chemoconvulsants-induced convulsions. However, its ability to delay the latency to seizures induced by pentylenetetrazole suggests that JB might be effective in the control of the seizure spread in epileptic brains.

Barriers to Seizure Management in Schools: Perceptions of School Nurses.

Science.gov (United States)

Terry, Debbie; Patel, Anup D; Cohen, Daniel M; Scherzer, Daniel; Kline, Jennifer

2016-12-01

The purpose of this study was to assess school nurses' perceptions of barriers to optimal management of seizures in schools. Eighty-three school nurses completed an electronic survey. Most agreed they felt confident they could identify a seizure (97.6%), give rectal diazepam (83.8%), and handle cluster seizures (67.1%), but fewer were confident they could give intranasal midazolam (63.3%), had specific information about a student's seizures (56.6%), or could swipe a vagus nerve stimulator magnet (47.4%). Nurses were more likely to be available at the time of a seizure in rural (17/20) (85%) versus suburban (21/34) (62%) or urban (8/25) (32%) schools (P = .001). School nurses are comfortable managing seizures in the school setting. However, a specific seizure plan for each child and education on intranasal midazolam and vagus nerve stimulator magnet use are needed. A barrier in urban schools is decreased availability of a nurse to identify seizures and administer treatment. © The Author(s) 2016.

Seizures Induced by Music

Directory of Open Access Journals (Sweden)

A. O. Ogunyemi

1993-01-01

Full Text Available Musicogenic epilepsy is a rare disorder. Much remains to be learned about the electroclinical features. This report describes a patient who has been followed at our institution for 17 years, and was investigated with long-term telemetered simultaneous video-EEG recordings. She began to have seizures at the age of 10 years. She experienced complex partial seizures, often preceded by elementary auditory hallucination and complex auditory illusion. The seizures occurred in relation to singing, listening to music or thinking about music. She also had occasional generalized tonic clonic seizures during sleep. There was no significant antecedent history. The family history was negative for epilepsy. The physical examination was unremarkable. CT and MRI scans of the brain were normal. During long-term simultaneous video-EEG recordings, clinical and electrographic seizure activities were recorded in association with singing and listening to music. Mathematical calculation, copying or viewing geometric patterns and playing the game of chess failed to evoke seizures.

Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

Science.gov (United States)

Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

2016-12-01

The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model.

Science.gov (United States)

Saha, Lekha; Bhandari, Swati; Bhatia, Alka; Banerjee, Dibyajyoti; Chakrabarti, Amitava

2014-12-01

Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats. In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study. In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats. These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy.

Controlled-release oxycodone-induced seizures.

Science.gov (United States)

Klein, Moti; Rudich, Zvia; Gurevich, Boris; Lifshitz, Matityahu; Brill, Silviu; Lottan, Michael; Weksler, Natan

2005-11-01

The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

International Nuclear Information System (INIS)

Cianfoni, A.; Caulo, M.; Cerase, A.; Della Marca, G.; Falcone, C.; Di Lella, G.M.; Gaudino, S.; Edwards, J.; Colosimo, C.

2013-01-01

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention

Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

Energy Technology Data Exchange (ETDEWEB)

Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

2013-11-01

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

Science.gov (United States)

Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

Massively multiplayer online role-playing game-induced seizures: a neglected health problem in Internet addiction.

Science.gov (United States)

Chuang, Yao-Chung

2006-08-01

As the Internet has become rapidly and widely integrated into society, Internet addiction has become a growing psychosocial problem. However, epileptic seizure, another out-of-the-ordinary health problem, is often neglected in this regard. Ten patients who experienced epileptic seizures while playing the newest genre of electronic games -- Massively Multiplayer Online Role-Playing Games (MMORPGs) -- were investigated. Patients were predominantly male young adults, and most of the events were generalized tonic-clonic seizures, myoclonic seizures, and absences. These patients should be categorized into idiopathic generalized epilepsies. Even though photosensitivity was an important factor, behavioral and higher mental activities also seemed to be significant seizure precipitants. Results demonstrated that MMORPG-induced seizures were not analogous to the ordinary video game-induced seizures. Significantly, an epileptic seizure warning did not always appear on the websites of MMORPGs and instructions for the software. While the prevalence of MMORPG-induced seizures remains unknown, it may exceed our expectations and impact our society. Not only for clinical neurologists but also for the primary physicians, educators, sociologists, and global online game publishers, there should be an awareness of this special form of reflex seizures in order to provide an appropriate health warning to MMORPG players.

Radiation-induced cranial nerve palsy

International Nuclear Information System (INIS)

Berger, P.S.; Bataini, J.P.

1977-01-01

Twenty-five patients with 35 cranial nerve palsies were seen at the Fondation Curie during follow-up after radical radiotherapy for head and neck tumors. The twelfth nerve was involved in 19 cases, the tenth in nine, and the eleventh in five; the fifth and second nerves were involved once each and in the same patient. The twelfth nerve was involved alone in 16 patients and the tenth nerve alone in three, with multiple nerves involved in the remaining six patients. The palsy was noted from 12 to 145 months after diagnosis of the tumor. The latency period could be correlated with dose so that the least square fit equation representing NSD vs delay is NSD = 2598--Delay (in months) x 4.6, with a correlation coefficient of -0.58. The distinction between tumor recurrence and radiation-induced nerve palsy is critical. It can often be inferred from the latency period but must be confirmed by observation over a period of time

Forced eye closure-induced reflex seizure and non-ketotic hyperglycemia

International Nuclear Information System (INIS)

Tiras, Raziye; Mutlu, Aytul; Ozben, Serkan; Aydemir Tuba; Ozerab, Feriha

2009-01-01

We report an uncommon case of 53-year-old female patient with partial seizure induced by forced voluntary eye closure due to non-ketotic hyperglycemia. The initial laboratory tests showed an elevated blood glucose level of 550 mg/dL but no evidence of ketosis. Brain magnetic resonance imaging was normal. When the blood glucose levels decreased slowly to about 150 mg/dL in five days, the seizures ended completely. No anticonvulsants were used. Since seizures are generally refractory to antiepileptic medication, control of blood glucose is essential. (author)

Capillary gas chromatographic analysis of nerve agents using large volume injections

NARCIS (Netherlands)

Degenhardt, C.E.A.M.; Kientz, C.E.

1996-01-01

The use of large volume injections has been studied for the verification of intact organophosphorus chemical warfare agents in water samples. As the use of ethyl acetate caused severe detection problems new potential solvents were evaluated. With the developed procedure, the nerve agents sarin,

Brain levels of N-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure

DEFF Research Database (Denmark)

Moesgaard, B.; Hansen, H.H.; Petersen, G.

2003-01-01

occur in response to seizure activity. Therefore, we investigated the effect of pentylenetetrazol (PTZ)-induced seizures in PTZ-kindled mice on the level of NAPE in the brain. Male NMRI mice were kindled with PTZ injections 3 times/wk, thereby developing clonic seizures in response to PTZ. Mice were...... killed within 30 min after the clonic seizure on the test day (12th injection) and the brains were collected. Eight species of NAPE were analyzed as the glycerophospho-N-acylethanolamines by high-performance liquid chromatography-coupled electrospray ionization mass spectrometry. No effect of the PTZ...... accumulate during seizure....

Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.

Science.gov (United States)

Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M

2015-08-01

In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.

Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents

Directory of Open Access Journals (Sweden)

Norman A. Saffra

2015-02-01

Full Text Available Optic nerve head drusen can be associated with peripapillary choroidal neovascularization, in both the pediatric and adult population. These membranes can involve the macula, causing significant visual loss. Herein, we present a case that required treatment with an anti-VEGF agent. The patient failed to respond to the initial agent, but subsequently responded to a change of agent. Adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans.

Complex Regional Pain Syndrome Revived by Epileptic Seizure Then Disappeared Soon during Treatment with Regional Intravenous Nerve Blockade: A Case Report

Directory of Open Access Journals (Sweden)

Masahiko Sumitani

2011-01-01

Full Text Available We present a case of complex regional pain syndrome (CRPS, in which symptoms, including burning pain and severe allodynia, were alleviated by using a regional intravenous nerve blockade (Bier block combined with physiotherapy, but reappeared following an epileptic seizure. Symptoms disappeared again following control of epileptic discharges, as revealed by single-photon emission computed tomography (SPECT and electroencephalography (EEG results. Although systemic toxicity of a local anesthetic applied by Bier block was suspected as a cause of the first seizure, the patient did not present any other toxic symptoms, and seizures repeatedly occurred after Bier block cessation; the patient was then diagnosed as having temporal symptomatic epilepsy. This case suggests that symptoms of CRPS may be sustained by abnormal brain conditions, and our findings contribute to the understanding of how the central nervous system participates in maintaining pain and allodynia associated with CRPS.

Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Zeid M Rusan

Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

Zinc movement in the brain under kainate-induced seizures.

Science.gov (United States)

Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

2003-05-01

On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

Energy Technology Data Exchange (ETDEWEB)

Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A., E-mail: lucille.a.lange@us.army.mil

2012-03-15

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

International Nuclear Information System (INIS)

Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A.

2012-01-01

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA A ) receptors. However, seizure activity itself causes the endocytosis of GABA A receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD 50 ; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an

Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

International Nuclear Information System (INIS)

Ghanem, Eman; Raushel, Frank M.

2005-01-01

Organophosphates have been widely used as insecticides and chemical warfare agents. The health risks associated with these agents have necessitated the need for better detoxification and bioremediation tools. Bacterial enzymes capable of hydrolyzing the lethal organophosphate nerve agents are of special interest. Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta displays a significant rate enhancement and substrate promiscuity for the hydrolysis of organophosphate triesters. Directed evolution and rational redesign of the active site of PTE have led to the identification of new variants with enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of organophosphate neurotoxins. PTE has been utilized to protect against organophosphate poisoning in vivo. Biotechnological applications of PTE for detection and decontamination of insecticides and chemical warfare agents are developing into useful tools. In this review, the catalytic properties and potential applications of this remarkable enzyme are discussed

Optimizing therapy of seizures in neurosurgery.

Science.gov (United States)

Michelucci, Roberto

2006-12-26

The use of antiepileptic drugs (AEDs) in the neurosurgical setting has a number of implications, including their possible role in the prevention of seizures after acute cerebral insults or brain tumors and the potential for toxicity and interactions when these agents are administered in association with radiotherapy or chemotherapy. This review discusses these controversial issues and draws the following conclusions. 1) AEDs should be prescribed on a short-term basis to prevent seizures occurring within the first week after a cerebral insult (trauma, neurosurgical procedure) but are ineffective to avoid true post-traumatic epilepsy or first seizures in patients with primary or secondary cerebral neoplasms. 2) The use of phenytoin and, to a lesser extent, phenobarbital and carbamazepine during cranial irradiation is associated with an increased risk for severe, potentially fatal, mucocutaneous reactions. In this context, new AEDs with a very low potential for allergic cutaneous reactions should be preferred. 3) Enzyme-inducing AEDs, such as phenytoin, phenobarbital, and carbamazepine, may increase the clearance and reduce the clinical efficacy of corticosteroids and anticancer agents that are also metabolized by the cytochrome P450 system. The newly developed AEDs that are devoid of hepatic metabolism, such as levetiracetam and gabapentin, are now recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents.

Febrile seizures

Science.gov (United States)

... proper care. Occasionally, a provider will prescribe a medicine called diazepam to prevent or treat febrile seizures that occur more than once. However, no drug is completely effective in preventing febrile seizures. Alternative Names Seizure - fever induced; Febrile convulsions Patient Instructions ...

The ontogeny of seizures induced by leucine-enkephalin and beta-endorphin.

Science.gov (United States)

Snead, O C; Stephens, H

1984-06-01

Rats ranging in postnatal age from 6 hours to 28 days were implanted with cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. We then administered varying amounts of the opiate peptides leucine-enkephalin and beta-endorphin intracerebroventricularly with continuous electroencephalographic monitoring. Leucine-enkephalin produced electrical seizure activity in rats as young as 2 days. beta-Endorphin administration was associated with seizures at the fifth postnatal day, with a high incidence of apnea resulting in death in animals as young as 6 hours. An adult seizure response to beta-endorphin and leucine-enkephalin was seen at 15 and 28 days of age, respectively. Naloxone blocked the seizure produced by these opiate peptides in all age groups. The data indicate that the opiate peptides are potent epileptogenic compounds in developing brain, that seizures induced by leucine-enkephalin differ from those caused by beta-endorphin, and that petit mal-like seizure activity can be an adult response in the rodent.

Improved identification of cranial nerves using paired-agent imaging: topical staining protocol optimization through experimentation and simulation

Science.gov (United States)

Torres, Veronica C.; Wilson, Todd; Staneviciute, Austeja; Byrne, Richard W.; Tichauer, Kenneth M.

2018-03-01

Skull base tumors are particularly difficult to visualize and access for surgeons because of the crowded environment and close proximity of vital structures, such as cranial nerves. As a result, accidental nerve damage is a significant concern and the likelihood of tumor recurrence is increased because of more conservative resections that attempt to avoid injuring these structures. In this study, a paired-agent imaging method with direct administration of fluorophores is applied to enhance cranial nerve identification. Here, a control imaging agent (ICG) accounts for non-specific uptake of the nerve-targeting agent (Oxazine 4), and ratiometric data analysis is employed to approximate binding potential (BP, a surrogate of targeted biomolecule concentration). For clinical relevance, animal experiments and simulations were conducted to identify parameters for an optimized stain and rinse protocol using the developed paired-agent method. Numerical methods were used to model the diffusive and kinetic behavior of the imaging agents in tissue, and simulation results revealed that there are various combinations of stain time and rinse number that provide improved contrast of cranial nerves, as suggested by optimal measures of BP and contrast-to-noise ratio.

Development of pretreatment compounds against nerve-gas agents. Annual report (Final), 16 May 88-30 Sep 90

Energy Technology Data Exchange (ETDEWEB)

Carroll, F.I.; Abraham, P.

1990-09-30

The U. S. Army Medical Research and Development Command is interested in research directed toward the development of countermeasures to chemical warfare (CW) agents such as the nerve gas poison soman. Soman and other nerve gas poisons are extremely potent cholinesterase inhibitors. This inhibition leads to a buildup of excess acetylcholine resulting in over-stimulation of both the peripheral and central nervous system and can lead to death. Standard therapy for organophosphate nerve agent poisoning is based on co-administration of an anticholinergic agent such as atropine to antagonize the effects of accumulated acetylcholine and a cholinesterase reactivator such as 2-PAM to dephosphorylate the inhibited enzyme. However, since many problems remain in the treatment of organophosphate nerve agent poisoning, there is considerable interest and need to develop new pretreatment and treatment drugs, particularly for soman poisoning.

Glutamate decarboxylase activity in rat brain during experimental epileptic seizures induced by pilocarpine

Energy Technology Data Exchange (ETDEWEB)

Netopilova, M; Drsata, J [Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, 50005 Hradec Kralove (Czech Republic); Haugvicova, R; Kubova, H; Mares, P [Institute of Physiology, Czech Academy of Sciences, 14220 Prague (Czech Republic)

1998-07-01

Glutamate decarboxylase (GAD) activity was studied rat brain parts in a pilocarpine model of epileptic seizures. An increased enzyme activity was found in hippocampus a cerebellum during the acute phase of seizures, while the cortex and cerebellum showed increased GAD activity in the chronic phase of the process. Systematic administration of pilocarpine to rats induces status epilepticus. The aim of this research was to find out if seizures induced by pilocarpine are connected changes in glutamate decarboxylase activity, the enzyme that catalyzes synthesis of inhibitory neurotransmitter GABA. GAD was assayed by means of radiometric method using {sup 14}C-carboxyl-labelled glutamate and measurement of {sup 14}CO{sub 2} radioactivity. Obtained results suggest that pilocarpine seizures are connected with changes of GAD activity in individual parts of rat brain. (authors)

Glutamate decarboxylase activity in rat brain during experimental epileptic seizures induced by pilocarpine

International Nuclear Information System (INIS)

Netopilova, M.; Drsata, J.; Haugvicova, R.; Kubova, H.; Mares, P.

1998-01-01

Glutamate decarboxylase (GAD) activity was studied rat brain parts in a pilocarpine model of epileptic seizures. An increased enzyme activity was found in hippocampus a cerebellum during the acute phase of seizures, while the cortex and cerebellum showed increased GAD activity in the chronic phase of the process. Systematic administration of pilocarpine to rats induces status epilepticus. The aim of this research was to find out if seizures induced by pilocarpine are connected changes in glutamate decarboxylase activity, the enzyme that catalyzes synthesis of inhibitory neurotransmitter GABA. GAD was assayed by means of radiometric method using 14 C-carboxyl-labelled glutamate and measurement of 14 CO 2 radioactivity. Obtained results suggest that pilocarpine seizures are connected with changes of GAD activity in individual parts of rat brain. (authors)

Recent advances in evaluation of oxime efficacy in nerve agent poisoning by in vitro analysis

International Nuclear Information System (INIS)

Worek, F.; Eyer, P.; Aurbek, N.; Szinicz, L.; Thiermann, H.

2007-01-01

The availability of highly toxic organophosphorus (OP) warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE). Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents, e.g. soman and cyclosarin. This led to the synthesis and investigation of numerous oximes in the past decades. Reactivation of OP-inhibited AChE is considered to be the most important reaction of oximes. Clinical data from studies with pesticide-poisoned patients support the assumption that the various reactions between AChE, OP and oxime, i.e. inhibition, reactivation and aging, can be investigated in vitro with human AChE. In contrast to animal experiments such in vitro studies with human tissue enable the evaluation of oxime efficacy without being affected by species differences. In the past few years numerous in vitro studies were performed by different groups with a large number of oximes and methods were developed for extrapolating in vitro data to different scenarios of human nerve agent poisoning. The present status in the evaluation of new oximes as antidotes against nerve agent poisoning will be discussed

Assessment of time interval between tramadol intake and seizure and second drug-induced attack

Directory of Open Access Journals (Sweden)

Bahareh Abbasi

2015-11-01

Full Text Available Background: Tramadol is a synthetic drug which is prescribed in moderate and severe pain. Tramadol overdose can induce severe complications such as consciousness impairment and convulsions. This study was done to determine the convulsions incidence after tramadol use until one week after hospital discharge. Methods: This prospective study was done in tramadol overdose patients without uncontrolled epilepsy and head injury history. All cases admitted in Loghman and Rasol Akram Hospitals, Tehran, Iran from 1, April 2011 to 1, April 2012 were included and observed for at least 12 hours. Time interval between tramadol intake and first seizure were record. Then, patients with second drug-induced seizure were recognized and log time between the first and second seizure was analyzed. The patients were transferred to the intensive care unit (ICU if clinical worsening status observed. One week after hospital discharge, telephone follow-up was conducted. Results: A total of 150 patients with a history of tramadol induced seizures (141 men, 9 women, age: 23.23±5.94 years were enrolled in this study. Convulsion was seen in 104 patients (69.3%. In 8 out of 104 patients (7.6% two or more convulsion was seen. Time interval between tramadol use and the onset of the first and second seizure were 0.93±0.17 and 2.5±0.75 hours, respectively. Tramadol induced seizures are more likely to occur in males and patients with a history of drug abuse. Finally, one hundred forty nine patients (99.3% were discharged with good condition and the only one patient died from tramadol overdose. Conclusion: The results of the study showed tramadol induced seizure most frequently occurred within the first 4 hours of tramadol intake. The chance of experiencing a second seizure exists in the susceptible population. Thus, 4 hours after drug intake is the best time for patients to be hospital discharged.

Modern management of epilepsy: Vagus nerve stimulation.

Science.gov (United States)

Ben-Menachem, E

1996-12-01

Vagus nerve stimulation (VNS) was first tried as a treatment for seizure patients in 1988. The idea to stimulate the vagus nerve and disrupt or prevent seizures was proposed by Jacob Zabarra. He observed a consistent finding among several animal studies which indicated that stimulation of the vagus nerve could alter the brain wave patterns of the animals under study. His hypothesis formed the basis for the development of the vagus nerve stimulator, an implantable device similar to a pacemaker, which is implanted in the left chest and attached to the left vagus nerve via a stimulating lead. Once implanted, the stimulator is programmed by a physician to deliver regular stimulation 24 hours a day regardless of seizure activity. Patients can also activate extra 'on-demand' stimulation with a handheld magnet. Clinical studies have demonstrated VNS therapy to be a safe and effective mode of treatment when added to the existing regimen of severe, refractory patients with epilepsy. Efficacy ranges from seizure free to no response with the majority of patients (> 50%) reporting at least a 50% improvement in number of seizures after 1.5 years of treatment. The side-effect profile is unique and mostly includes stimulation-related sensations in the neck and throat. The mechanism of action for VNS is not clearly understood although two theories have emerged. First, the direct connection theory hypothesizes that the anticonvulsant action of VNS is caused by a threshold raising effect of the connections to the nucleus of the solitary tract and on to other structures. The second is the concept that chronic stimulation of the vagus nerve increases the amount of inhibitory neurotransmitters and decreases the amount of excitatory neurotransmitters. Additional research into the optimal use of VNS is ongoing. Animal and clinical research have produced some interesting new data suggesting there are numerous ways to improve the clinical performance of vagus nerve stimulation as a

Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

Energy Technology Data Exchange (ETDEWEB)

Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.; Ioradanis, G.; Dewey, S.L.; Agzzid, A.; Heppnerd, F.L.; Tsirka, St.E.

2010-04-01

Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.

The study of ictal brain SPECT during seizures induced by clonidine and sleep-deprivation in patients with epilepsy

International Nuclear Information System (INIS)

Wang Xiaohui; Chen Xuehong; Wang Zhengjiang; Liu Jiangyan; Feng Jianzhong; Ye Jiang; Zhao Li

2010-01-01

Objective: To evaluate the feasibility and clinical value of combined clonidine and sleep-deprivation induced seizures for ictal brain SPECT imaging in patients with epilepsy. Methods: Fifty-two epilepsy patients were given oral clonidine plus sleep-deprivation to induce seizures with video-electroencephalogram (VEEG) monitoring. Forty-seven patients were selected as control group, whose seizures were induced by sleep-deprivation only. 99 Tc m -ethylcysteinate dimer (ECD) was injected within 30 s since a clinical sign and/or a typical EEG discharge of epilepsy was recognized. Brain SPECT was performed 30 min after 99 Tc m -ECD injection. χ 2 -test was performed by using software SPSS 10.0. Results: One to two hr after oral intake of clonidine plus sleep-deprivation, 75% (39/52) patients were induced seizures, including 92.3% (36/39) with subclinical seizures and 7.7% (3/39) with clinical seizures. Ictal brain SPECT localized the lesions with high uptake of 99 Tc m -ECD in 37 (94.9%) patients. In control group, 38.3% (18/47) were induced epileptic seizures, including 77.8% (14/18) with subclinical seizures and 22.2% (4/18) with clinical seizures. The induction rate of epileptic seizures in clonidine plus sleep-deprivation group was significantly higher than that of control group (χ 2 = 13.614, P 2 = 1.253, P>0.05). Conclusions: The combination of oral intake of clonidine and sleep-deprivation could increase the induction rate of epileptic seizures and it is effective for epilepsy SPECT imaging. (authors)

Characterization of seizures induced by acute exposure to an organophosphate herbicide, glufosinate-ammonium.

Science.gov (United States)

Calas, André-Guilhem; Perche, Olivier; Richard, Olivier; Perche, Astrid; Pâris, Arnaud; Lauga, Fabien; Herzine, Ameziane; Palomo, Jennifer; Ardourel, Marie-Yvonne; Menuet, Arnaud; Mortaud, Stéphane; Pichon, Jacques; Montécot-Dubourg, Céline

2016-05-04

Glufosinate-ammonium (GLA), the active component of a widely used herbicide, induces convulsions in rodents and humans. In mouse, intraperitoneal treatment with 75 mg/kg GLA generates repetitive tonic-clonic seizures associated with 100% mortality within 72 h after treatment. In this context, we characterized GLA-induced seizures, their histological consequences and the effectiveness of diazepam treatment. Epileptic discharges on electroencephalographic recordings appeared simultaneously in the hippocampus and the cerebral cortex. Diazepam treatment at 6 h immediately stopped the seizures and prevented animal death. However, intermittent seizures were recorded on electroencephalogram from 6 h after diazepam treatment until 24 h, but had disappeared after 15 days. In our model, neuronal activation (c-Fos immunohistochemistry) was observed 6 h after GLA exposure in the dentate gyrus, CA1, CA3, amygdala, piriform and entorhinal cortices, indicating the activation of the limbic system. In these structures, Fluoro-Jade C and Cresyl violet staining did not show neuronal suffering. However, astroglial activation was clearly observed at 24 h and 15 days after GLA treatment in the amygdala, piriform and entorhinal cortices by PCR quantitative, western blot and immunohistochemistry. Concomitantly, glutamine synthetase mRNA expression (PCR quantitative), protein expression (western blot) and enzymatic activity were upregulated. In conclusion, our study suggests that GLA-induced seizures: (a) involved limbic structures and (b) induced astrocytosis without neuronal degeneration as an evidence of a reactive astrocyte beneficial effect for neuronal protection.

Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide

Directory of Open Access Journals (Sweden)

Russell P Saneto

2009-03-01

Full Text Available Russell P Saneto1, Gail D Anderson21Division of Pediatric Neurology, Seattle Children’s Hospital/University of Washington, Seattle, Washington, USA; 2Department of Pharmacy, University of Washington, Seattle, Washington, USAAbstract: Lennox-Gaustaut syndrome is an electroclinical epilepsy syndrome characterized by the triad of electroencephalogram showing diffuse slow spike-and-wave discharges and paroxysmal fast activity, multiple intractable seizure types, and cognitive impairment. The intractability to seizure medications and cognitive impairment gives rise to eventual institutionalized patient care. Only a small subset of seizure medications has been shown to be helpful in seizure control. Most patients take up to 3 medications at high therapeutic dosing and are susceptible to medication-induced side effects. The lack of medication efficacy in seizure control has led one meta-analysis to conclude that there is no single medication that is highly efficacious in controlling seizures in this syndrome. On this background, a new and structurally novel seizure medication, rufinamide, has been found to be beneficial in the treatment of seizures in this syndrome. In a multicenter, double-blinded, randomized, placebo-controlled study, rufinamide was found to reduce seizures by over 30%. More importantly, it reduced the frequency of the seizure type that induces most of the morbidity of this syndrome, the drop seizure, by over 40%. There were few side effects, the medication was well tolerated, and in the open labeled extension study, tolerance was not found. In this review, we describe the main electroclinical features of Lennox-Gaustaut syndrome and summarize the few controlled studies that have contributed to its rational treatment. Currently, there is no single agent or combination of agents that effectively treat the multiple seizure types and co-morbidities in this syndrome. Our focus will be on the role of the new medication rufinamide in

Magnetic resonance imaging in kainic acid-induced limbic seizure status in cats

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Shigeya; Tanaka, Tatsuya; Fukuda, Hiroshi; Yonemasu, Yukichi [Asahikawa Medical Coll., Hokkaido (Japan); Kondo, Shinji; Hori, Tomokatsu; Tanaka, Mitsuru; Shindo, Kazuyuki

1993-05-01

Magnetic resonance imaging before, during, and after kainic acid (KA)-induced limbic seizure status in cats demonstrated the bilateral hippocampi as slightly high-intensity areas on the T[sub 2]-weighted images during the limbic seizure status, and isointensity areas 1-2 weeks after KA injection when the limbic seizure status subsided. However, the hippocampi again became high-intense 1-3 months after KA injection. Histological study suggested that the high-intensity area during the limbic seizure status resulted from regional edema, and in the chronic period from marked gliosis and/or atrophic change as a consequence of tissue damage in the hippocampus. (author).

A hypothesis regarding the molecular mechanism underlying dietary soy-induced effects on seizure propensity.

Directory of Open Access Journals (Sweden)

Cara Jean Westmark

2014-09-01

Full Text Available Numerous neurological disorders including fragile X syndrome, Down syndrome, autism and Alzheimer’s disease are comorbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.

Antiseizure effects of ketogenic diet on seizures induced with ...

African Journals Online (AJOL)

Antiseizure effects of ketogenic diet on seizures induced with pentylenetetrazole, 4-aminopyridine and strychnine in wistar rats. E.O. Sanya, A.O. Soladoye, O.O. Desalu, P.M. Kolo, L. A. Olatunji, J.K. Olarinoye ...

Evaluation of oxime efficacy in nerve agent poisoning: Development of a kinetic-based dynamic model

International Nuclear Information System (INIS)

Worek, Franz; Szinicz, Ladislaus; Eyer, Peter; Thiermann, Horst

2005-01-01

The widespread use of organophosphorus compounds (OP) as pesticides and the repeated misuse of highly toxic OP as chemical warfare agents (nerve agents) emphasize the necessity for the development of effective medical countermeasures. Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. From obvious ethical reasons only animal experiments can be used to evaluate new oximes as nerve agent antidotes. However, the extrapolation of data from animal to humans is hampered by marked species differences. Since reactivation of OP-inhibited AChE is considered to be the main mechanism of action of oximes, human erythrocyte AChE can be exploited to test the efficacy of new oximes. By combining enzyme kinetics (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics a dynamic in vitro model was developed which allows the calculation of AChE activities at different scenarios. This model was validated with data from pesticide-poisoned patients and simulations were performed for intravenous and percutaneous nerve agent exposure and intramuscular oxime treatment using published data. The model presented may serve as a tool for defining effective oxime concentrations and for optimizing oxime treatment. In addition, this model can be useful for the development of meaningful therapeutic animal models

The chemical induction of seizures in psychiatric therapy: were flurothyl (indoklon) and pentylenetetrazol (metrazol) abandoned prematurely?

Science.gov (United States)

Cooper, Kathryn; Fink, Max

2014-10-01

Camphor-induced and pentylenetetrazol-induced brain seizures were first used to relieve psychiatric illnesses in 1934. Electrical inductions (electroconvulsive therapy, ECT) followed in 1938. These were easier and less expensive to administer and quickly became the main treatment method. In 1957, seizure induction with the inhalant anesthetic flurothyl was tested and found to be clinically effective.For many decades, complaints of memory loss have stigmatized and inhibited ECT use. Many variations of electricity in form, electrode placement, dosing, and stimulation method offered some relief, but complaints still limit its use. The experience with chemical inductions of seizures was reviewed based on searches for reports of each agent in Medline and in the archival files of original studies by the early investigators. Camphor injections were inefficient and were rapidly replaced by pentylenetetrazol. These were effective but difficult to administer. Flurothyl inhalation-induced seizures were as clinically effective as electrical inductions with lesser effects on memory functions. Flurothyl inductions were discarded because of the persistence of the ethereal aroma and the fears induced in the professional staff that they might seize. Persistent complaints of memory loss plague electricity induced seizures. Flurothyl induced seizures are clinically as effective without the memory effects associated with electricity. Reexamination of seizure inductions using flurothyl in modern anesthesia facilities is encouraged to relieve medication-resistant patients with mood disorders and catatonia.

Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

Science.gov (United States)

Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

2016-05-01

Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

Science.gov (United States)

Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

2012-01-01

As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

MR imaging findings of generalized tonic clonic seizure induced brain changes

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Ah; Chung, Jin Il; Yonn, Pyeong Ho; Kim, Dong Ik; Chung, Tae Sub; Kim, Joo Hee [College of Medicine, Yonsei Unversity, Seoul (Korea, Republic of)

2000-03-01

To evaluate MRI signal changes in the brain induced by generalized tonic clonic seizure. Six patients who underwent MRI within three days of generalized tonic clonic seizure were retrospectively reviewed. Diffusion -weighted images were added in three patients during initial examination, and in six, the follow-up MRI was performed nine days to five months after the onset of seizure. We evaluated the patterns of signal change, location of the lesion and degree of contrast enhancement, and the signal change seen on diffusion weighted images. We also compared the signal changes seen on initial and follow-up MRI. In all six patients, MR images showed focally increased T2 signal intensity, and swelling and increased volume of the involved cortical gyrus. In five, the lesion was mainly located in the cortical gray matter and subcortical white matter; namely, in the bilateral cingulate gyri, and the bilateral parieto-occipital, left parietal, left frontoparietal, and left temporal lobe. In the remaining patient, the lesion was located in the right hippocampus. Two patients showed bilateral lesions and one showed multiple lesions. In four patients, T1-weighted images revealed decreased signal intensity of the same location, and in one, gyral contrast enhancement was noted. On diffusion-weighted images, three patients showed increased signal intensity. Follow-up MRI demonstrated complete resolution of the abnormal signal change (n=3D5), or a decrease (n=3D1). A transient increase in MR signal intensity with increased volume was noted in cortical and subcortical white matter after generalized tonic clonic seizure. This finding reflects the vasogenic and cytotoxic edema induced by seizure and can help exclude etiologic lesions such as tumors, inflammation and demyelinating disease that induce epilepsy. (author)

MR imaging findings of generalized tonic clonic seizure induced brain changes

International Nuclear Information System (INIS)

Kim, Jeong Ah; Chung, Jin Il; Yonn, Pyeong Ho; Kim, Dong Ik; Chung, Tae Sub; Kim, Joo Hee

2000-01-01

To evaluate MRI signal changes in the brain induced by generalized tonic clonic seizure. Six patients who underwent MRI within three days of generalized tonic clonic seizure were retrospectively reviewed. Diffusion -weighted images were added in three patients during initial examination, and in six, the follow-up MRI was performed nine days to five months after the onset of seizure. We evaluated the patterns of signal change, location of the lesion and degree of contrast enhancement, and the signal change seen on diffusion weighted images. We also compared the signal changes seen on initial and follow-up MRI. In all six patients, MR images showed focally increased T2 signal intensity, and swelling and increased volume of the involved cortical gyrus. In five, the lesion was mainly located in the cortical gray matter and subcortical white matter; namely, in the bilateral cingulate gyri, and the bilateral parieto-occipital, left parietal, left frontoparietal, and left temporal lobe. In the remaining patient, the lesion was located in the right hippocampus. Two patients showed bilateral lesions and one showed multiple lesions. In four patients, T1-weighted images revealed decreased signal intensity of the same location, and in one, gyral contrast enhancement was noted. On diffusion-weighted images, three patients showed increased signal intensity. Follow-up MRI demonstrated complete resolution of the abnormal signal change (n=3D5), or a decrease (n=3D1). A transient increase in MR signal intensity with increased volume was noted in cortical and subcortical white matter after generalized tonic clonic seizure. This finding reflects the vasogenic and cytotoxic edema induced by seizure and can help exclude etiologic lesions such as tumors, inflammation and demyelinating disease that induce epilepsy. (author)

Mapping brain activity on the verge of a photically induced generalized tonic-clonic seizure

DEFF Research Database (Denmark)

Moeller, Friederike; Siebner, Hartwig R; Wolff, Stephan

2009-01-01

In a photosensitive patient intermittent photic stimulation (IPS) accidentally provoked a generalized tonic-clonic seizure during simultaneous recordings of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Before seizure onset, IPS consistently induced generalized...

Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

Directory of Open Access Journals (Sweden)

P S Santos

2011-01-01

Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

Science.gov (United States)

Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

2011-10-01

4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

Seizure Prediction and its Applications

Science.gov (United States)

Iasemidis, Leon D.

2011-01-01

Epilepsy is characterized by intermittent, paroxysmal, hypersynchronous electrical activity, that may remain localized and/or spread and severely disrupt the brain’s normal multi-task and multi-processing function. Epileptic seizures are the hallmarks of such activity and had been considered unpredictable. It is only recently that research on the dynamics of seizure generation by analysis of the brain’s electrographic activity (EEG) has shed ample light on the predictability of seizures, and illuminated the way to automatic, prospective, long-term prediction of seizures. The ability to issue warnings in real time of impending seizures (e.g., tens of minutes prior to seizure occurrence in the case of focal epilepsy), may lead to novel diagnostic tools and treatments for epilepsy. Applications may range from a simple warning to the patient, in order to avert seizure-associated injuries, to intervention by automatic timely administration of an appropriate stimulus, for example of a chemical nature like an anti-epileptic drug (AED), electromagnetic nature like vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial direct current (TDC) or transcranial magnetic stimulation (TMS), and/or of another nature (e.g., ultrasonic, cryogenic, biofeedback operant conditioning). It is thus expected that seizure prediction could readily become an integral part of the treatment of epilepsy through neuromodulation, especially in the new generation of closed-loop seizure control systems. PMID:21939848

Histopathology of cryoballoon ablation-induced phrenic nerve injury.

Science.gov (United States)

Andrade, Jason G; Dubuc, Marc; Ferreira, Jose; Guerra, Peter G; Landry, Evelyn; Coulombe, Nicolas; Rivard, Lena; Macle, Laurent; Thibault, Bernard; Talajic, Mario; Roy, Denis; Khairy, Paul

2014-02-01

Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described. A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups. Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage. © 2013 Wiley Periodicals, Inc.

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

Science.gov (United States)

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures

International Nuclear Information System (INIS)

Chang, Y.F.; Hargest, V.; Chen, J.S.

1988-01-01

L-lysine and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine of L-Pa i.p. significantly increased clonic and tonic latencies in a dose-dependent manner against 90 mg/kg PTZ-induced seizures. L-Lysine but not L-Pa enhanced the anticonvulsant effect of diazepam (DZ). L-Pa i.c.v. showed a slight decrease in clonic latency; it did not enhance the antiseizure activity of DZ; it caused seizures at 0.6 mmol/kg. D-PA i.c.v. displayed an opposite effect compared to its L-isomer. The anticonvulsant effect of L-lysine in terms of increase in seizure latency and survival was even more amplified when tested with a submaximal PTZ concentration. L-Lysine showed an enhancement of specific 3 H-flunitrazepam(FZ) binding to mouse brain membranes both in vitro an din vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of 3 H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor

Quantification of VX Nerve Agent in Various Food Matrices by Solid-Phase Extraction Ultra-Performance Liquid ChromatographyTime-of-Flight Mass Spectrometry

Science.gov (United States)

2016-04-01

QUANTIFICATION OF VX NERVE AGENT IN VARIOUS FOOD MATRICES BY SOLID - PHASE EXTRACTION ULTRA-PERFORMANCE...TITLE AND SUBTITLE Quantification of VX Nerve Agent in Various Food Matrices by Solid - Phase Extraction Ultra-Performance Liquid Chromatography...QUANTIFICATION OF VX NERVE AGENT IN VARIOUS FOOD MATRICES BY SOLID - PHASE EXTRACTION ULTRA-PERFORMANCE LIQUID CHROMATOGRAPHY–TIME-OF-FLIGHT MASS

Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

Science.gov (United States)

Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

2008-09-25

Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

Radiation-induced cranial nerve palsy: hypoglossal nerve and vocal cord palsies

International Nuclear Information System (INIS)

Takimoto, Toru; Saito, Yasuo; Suzuki, Masayuki; Nishimura, Toshirou

1991-01-01

Cranial nerve palsies are an unexpected complication of radiotherapy for head and neck tumours. We present a case of this radiation-induced cranial palsy. An 18-year-old female with nasopharyngeal carcinoma developed a right hypoglossal nerve palsy 42 months after cancericidal doses of radiotherapy. In addition, she developed a bilateral vocal cord palsy 62 months after the therapy. Follow-up over four years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement. (author)

Assessing Anticonvulsant Effect of Aqueous Extract of Datura Stramonium Seed on PTZ-Induced Seizures in the Male Mice

Directory of Open Access Journals (Sweden)

S Namvar Aghdash

2015-11-01

Full Text Available Background: Epilepsy is one of the most common neurological disorders that affect social, economic and biological aspects of the human life. Many epileptic patients have uncontrolled seizures and medication-related side effects despite adequate pharmacological treatment. The use of plant extracts is proposed as a therapeutic modality in order to treat different diseases. Datura plant has long been used in the traditional medicine in regard with some nervous disorders like epilepsy. Thus, this study aimed to provide a scientific basis investigating the effect of Datura aqueous extract on PTZ-induced seizures in the male mice. Methods: In this experimental study, 40 male mice were randomly allocated into 5 equal groups including: one control group, one sham group and three experimental groups. The experimental groups received 50, 100 and 150 mg/kg of aqueous extract of Datura Stramonium seed via gavage for 30 days, and the sham group received stilled water via gavage. Pentylenetetrazol (PTZ 35 mg/kg, i.p were injected into control, sham and experimental groups 30 minutes after gavage in order to induce the seizure. Then latency time of seizure onset, seizure duration and seizure phases were measured and recorded in the experimental, sham and control groups. The data analysis was carried out via one way ANOVA and Tukey post-hoc tests.  Moreover, difference less than 0.05 (P<0.05 was considered significant. Results: The study findings revealed that the aqueous extract of Datura Stramonium seed produced a significant effect on PTZ-induced seizure. In addition, Datura increases latency time of seizure onset (P˂0.01, inhibits progress of seizure stages (P˂0.05 and decreases seizure duration (P˂0.001. Conclusion: The results obtained from the present study indicated that extract of this plant has anticonvulsant effects on PTZ-induced seizure. As a result, it seems to be beneficial to the epilepsy treatment.

Pilocarpine-induced seizure-like activity with increased BNDF and neuropeptide Y expression in organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Poulsen, Frantz Rom; Jahnsen, Henrik; Blaabjerg, Morten

2002-01-01

Organotypic hippocampal slice cultures were treated with the muscarinic agonist pilocarpine to study induced seizure-like activity and changes in neurotrophin and neuropeptide expression. For establishment of a seizure-inducing protocol, 2-week-old cultures derived from 6-8-day-old rats were...

Treating acute seizures with benzodiazepines: does seizure duration matter?

Science.gov (United States)

Naylor, David E

2014-10-01

Several clinical trials have shown improved seizure control and outcome by early initiation of treatment with benzodiazepines, before arrival in the emergency department and before intravenous access can be established. Here, evidence is provided and reviewed for rapid treatment of acute seizures in order to avoid the development of benzodiazepine pharmacoresistance and the emergence of self-sustaining status epilepticus. Alterations in the physiology, pharmacology, and postsynaptic level of GABA-A receptors can develop within minutes to an hour and hinder the ability of synaptic inhibition to stop seizures while also impairing the efficacy of GABAergic agents, such as benzodiazepines, to boost impaired inhibition. In addition, heightened excitatory transmission further exacerbates the inhibitory/excitatory balance and makes seizure control even more resistant to treatment. The acute increase in the surface expression of NMDA receptors during prolonged seizures also may cause excitotoxic injury, cell death, and other pathological expressions and re-arrangements of receptor subunits that all contribute to long-term sequelae such as cognitive impairment and chronic epilepsy. In conclusion, a short window of opportunity exists when seizures are maximally controlled by first-line benzodiazepine treatment. After that, multiple pathological mechanisms quickly become engaged that make seizures increasingly more difficult to control with high risk for long-term harm.

Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

Science.gov (United States)

Thomas, J; Nores, W L; Pariser, R

1993-07-01

The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

A structure-activity analysis of the variation in oxime efficacy against nerve agents

International Nuclear Information System (INIS)

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz; Sweeney, Richard E.

2008-01-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k r2 ) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and in vitro k r2 decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 ( r2 as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k r2 · [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy

Advances in toxicology and medical treatment of chemical warfare nerve agents

Science.gov (United States)

2012-01-01

Organophosphorous (OP) Nerve agents (NAs) are known as the deadliest chemical warfare agents. They are divided into two classes of G and V agents. Most of them are liquid at room temperature. NAs chemical structures and mechanisms of actions are similar to OP pesticides, but their toxicities are higher than these compounds. The main mechanism of action is irreversible inhibition of Acetyl Choline Esterase (AChE) resulting in accumulation of toxic levels of acetylcholine (ACh) at the synaptic junctions and thus induces muscarinic and nicotinic receptors stimulation. However, other mechanisms have recently been described. Central nervous system (CNS) depression particularly on respiratory and vasomotor centers may induce respiratory failure and cardiac arrest. Intermediate syndrome after NAs exposure is less common than OP pesticides poisoning. There are four approaches to detect exposure to NAs in biological samples: (I) AChE activity measurement, (II) Determination of hydrolysis products in plasma and urine, (III) Fluoride reactivation of phosphylated binding sites and (IV) Mass spectrometric determination of cholinesterase adducts. The clinical manifestations are similar to OP pesticides poisoning, but with more severity and fatalities. The management should be started as soon as possible. The victims should immediately be removed from the field and treatment is commenced with auto-injector antidotes (atropine and oximes) such as MARK I kit. A 0.5% hypochlorite solution as well as novel products like M291 Resin kit, G117H and Phosphotriesterase isolated from soil bacterias, are now available for decontamination of NAs. Atropine and oximes are the well known antidotes that should be infused as clinically indicated. However, some new adjuvant and additional treatment such as magnesium sulfate, sodium bicarbonate, gacyclidine, benactyzine, tezampanel, hemoperfusion, antioxidants and bioscavengers have recently been used for OP NAs poisoning. PMID:23351280

REMOTE BIOSENSOR FOR IN SITU MONITORING OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

Science.gov (United States)

A remote electrochemical biosensor for field monitoring of organophosphate nerve agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a submersible amperometric probe design. This combination resu...

Seizure detection algorithms based on EMG signals

DEFF Research Database (Denmark)

Conradsen, Isa

Background: the currently used non-invasive seizure detection methods are not reliable. Muscle fibers are directly connected to the nerves, whereby electric signals are generated during activity. Therefore, an alarm system on electromyography (EMG) signals is a theoretical possibility. Objective...... on the amplitude of the signal. The other algorithm was based on information of the signal in the frequency domain, and it focused on synchronisation of the electrical activity in a single muscle during the seizure. Results: The amplitude-based algorithm reliably detected seizures in 2 of the patients, while...... the frequency-based algorithm was efficient for detecting the seizures in the third patient. Conclusion: Our results suggest that EMG signals could be used to develop an automatic seizuredetection system. However, different patients might require different types of algorithms /approaches....

A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy

Science.gov (United States)

Grabenstatter, Heidi L.; Dudek, F. Edward

2010-01-01

Purpose Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs). The purpose of the present study was to evaluate the efficacy of carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy. Methods Repeated, low-dose (5 mg/kg), intraperitoneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h. Five 1-month trials (n= 8–10 rats) assessed the effects of 0.3, 1, 3, 10 and 30 mg/kg carisbamate on spontaneous seizures. Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Results Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h post-drug epoch in 7 of 8 animals at 30 mg/kg. The effects of carisbamate (0.3–30 mg/kg) on spontaneous motor seizures appeared dose dependent. Conclusions These data support the hypothesis that a repeated-measures, cross-over protocol in animal models with spontaneous seizures is an effective method for testing AEDs. Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy. PMID:18494790

Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

International Nuclear Information System (INIS)

Gilat, E.; Kadar, T.; Levy, A.; Rabinovitz, I.; Cohen, G.; Kapon, Y.; Sahar, R.; Brandeis, R.

2005-01-01

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 ± 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 ± 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted in

Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: An electrographic, behavioral, and histological study in freely moving rats

Energy Technology Data Exchange (ETDEWEB)

Gilat, E [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Kadar, T [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Levy, A [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Rabinovitz, I [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Cohen, G [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Kapon, Y [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Sahar, R [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel); Brandeis, R [Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100 (Israel)

2005-11-15

Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsant effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA resulted

Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

Directory of Open Access Journals (Sweden)

Nian Yu

2011-01-01

Full Text Available This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA- induced seizure rats. Male SD rats were divided into saline control group (NS group, KA induced epilepsy group (EP group, and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group or with dexamethasone (DEX group. No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.

Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world.

Science.gov (United States)

Devereaux, Asha; Amundson, Dennis E; Parrish, J S; Lazarus, Angeline A

2002-10-01

Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.

50 CFR 12.5 - Seizure by other agencies.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Seizure by other agencies. 12.5 Section 12... SEIZURE AND FORFEITURE PROCEDURES General Provisions § 12.5 Seizure by other agencies. Any authorized... the laws listed in § 12.2 will, if so requested, deliver such seizure to the appropriate Special Agent...

Automatic and remote controlled ictal SPECT injection for seizure focus localization by use of a commercial contrast agent application pump.

Science.gov (United States)

Feichtinger, Michael; Eder, Hans; Holl, Alexander; Körner, Eva; Zmugg, Gerda; Aigner, Reingard; Fazekas, Franz; Ott, Erwin

2007-07-01

In the presurgical evaluation of patients with partial epilepsy, the ictal single photon emission computed tomography (SPECT) is a useful noninvasive diagnostic tool for seizure focus localization. To achieve optimal SPECT scan quality, ictal tracer injection should be carried out as quickly as possible after the seizure onset and under highest safety conditions possible. Compared to the commonly used manual injection, an automatic administration of the radioactive tracer may provide higher quality standards for this procedure. In this study, therefore, we retrospectively analyzed efficiency and safety of an automatic injection system for ictal SPECT tracer application. Over a 31-month period, 26 patients underwent ictal SPECT by use of an automatic remote-controlled injection pump originally designed for CT-contrast agent application. Various factors were reviewed, including latency of ictal injection, radiation safety parameters, and ictal seizure onset localizing value. Times between seizure onset and tracer injection ranged between 3 and 48 s. In 21 of 26 patients ictal SPECT supported the localization of the epileptogenic focus in the course of the presurgical evaluation. In all cases ictal SPECT tracer injection was performed with a high degree of safety to patients and staff. Ictal SPECT by use of a remote-controlled CT-contrast agent injection system provides a high scan quality and is a safe and confirmatory presurgical evaluation technique in the epilepsy-monitoring unit.

Peripheral nerve injury induces glial activation in primary motor cortex

Directory of Open Access Journals (Sweden)

Julieta Troncoso

2015-02-01

Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

Science.gov (United States)

Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

2014-01-01

Non-clinical seizure liability studies typically aim to: 1) confirm the nature of EEG activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally characterize several of these items in a three species comparative study. Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol (PTZ) was used to determine seizure threshold or as a positive seizurogenic agent. Clinical signs were recorded and premonitory signs were evaluated. In complement, other pharmacological agents were used to illustrate various safety testing strategies. Intravenous PTZ doses required to induce clonic convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs, cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical signs typically included decreased physical activity, enhanced physiological tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz), and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM) increased power in high (14-127Hz), and attenuated power in low (1-13Hz) frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and anticonvulsants, respectively. Telemetry video-EEG for seizure liability investigations was characterized in three species. Rats represent a first-line model in seizure liability assessments. Beagle dogs are often associated with overt susceptibility to seizure and are typically used in seizure liability studies only if

Successful switch from bilateral brief pulse to right unilateral ultrabrief pulse electroconvulsive therapy after failure to induce seizures

Directory of Open Access Journals (Sweden)

Kawashima H

2018-02-01

Full Text Available Hirotsugu Kawashima,1 Yuko Kobayashi,1 Taro Suwa,2 Toshiya Murai,2 Ryuichi Yoshioka1 1Department of Psychiatry, Toyooka Hospital, Toyooka, Hyogo, Japan; 2Department of Neuropsychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan Abstract: Inducing adequate therapeutic seizures during electroconvulsive therapy (ECT is sometimes difficult due to a high seizure threshold, even at the maximum stimulus charge. Previous studies have demonstrated that seizure threshold is lower in patients treated with right unilateral ultrabrief pulse (RUL-UBP ECT than in those treated with bilateral or brief pulse (BL-BP ECT. Therefore, switching to RUL-UBP ECT may be beneficial for patients in whom seizure induction is difficult with conventional ECT. In the present report, we discuss the case of a patient suffering from catatonic schizophrenia in whom BL-BP ECT failed to induce seizures at the maximum charge. However, RUL-UBP ECT successfully elicited therapeutic seizures and enabled the patient to achieve complete remission. This case illustrates that, along with other augmentation strategies, RUL-UBP ECT represents an alternative for seizure induction in clinical practice. Keywords: electroconvulsive therapy, augmentation, ultrabrief pulse, electrode placement, seizure threshold

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

Energy Technology Data Exchange (ETDEWEB)

Kaminski, Rafal M [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Blaszczak, Piotr [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Dekundy, Andrzej [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Parada-Turska, Jolanta [Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland); Calderazzo, Lineu [Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil); Cavalheiro, Esper A [Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil); Turski, Waldemar A [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland)

2007-03-15

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

International Nuclear Information System (INIS)

Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A.; Turski, Waldemar A.

2007-01-01

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality

Evaluation of Veriox as a Skin Decontamination Product after Dermal Exposure to the Nerve Agent VX

Science.gov (United States)

2016-09-01

was to determine whether Veriox® had efficacy as a decontamination product (DC) after skin exposure to the chemical warfare agent VX. This study...countermeasure, decontamination , RSDL, VX, nerve agent, cutaneous exposure, chemical warfare agent 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...invested considerable resources in developing detectors, protective garments, and products to remove and/or decontaminate chemical agent exposure on

In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

Science.gov (United States)

2012-01-01

nerve agents, such as sarin (GB), cyclosarin (GF), and VX, are potent inhibitors of the enzyme cholinesterase (ChE). Their toxic effects are due to...three nerve agents. Keywords: acetylcholinesterase; brain; cholinesterase inhibition; cholinesterase reactivation; cyclosarin; diacetylmonoxime...attributed, at least in part, to nuclophilic impedance [Ekstrom et al., 2006a; b; Hoskovcova et al., 2007]. Other AChE- inhibitors , such as soman, become

Capillary gas chromatographic analysis of nerve agents using large volume injections. Final report

Energy Technology Data Exchange (ETDEWEB)

Deinum, T.; Nieuwenhuy, C.

1994-11-01

The procedure developed at TNO-Prins Maurits Laboratory (TNO-PML) for the verification of intact organophosphorus chemical warfare agents in water samples was improved. The last step in this procedure, the laborious and non-reproducible transfer of an ethyl acetate extract onto a Tenax-adsorption tube followed by thermal desorption of the Tenax-tube, was replaced by large volume injection of the extract onto a capillary gas chromatographic system. The parameters controlling the injection of a large volume of an extract (200 ul) were investigated and optimized. As ethyl acetate caused severe problems, potential new solvents were evaluated. With the improved procedure, the nerve agents sarin, tabun, soman, diisopropyl fluorophosphate (DFP) and VX could be determined in freshly prepared water samples at pg/ml (ppt) levels. The fate of the nerve agents under study in water at two pH`s (4.8 and 6) was investigated. For VX, the pH should be adjusted before extraction. Moreover, it is worthwhile to acidify water samples to diminish hydrolysis.

27 CFR 555.186 - Seizure or forfeiture.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Seizure or forfeiture. 555... Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U.S.C. 842(l)-(n) is subject to seizure and forfeiture, and all provisions of 19 U.S.C. 1595a...

High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

Science.gov (United States)

Laorden, M L; Miralles, F S; Puig, M M

1988-03-01

The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

A new model to study sleep deprivation-induced seizure.

Science.gov (United States)

Lucey, Brendan P; Leahy, Averi; Rosas, Regine; Shaw, Paul J

2015-05-01

A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB(9ed4)), and in an adult temperature sensitive seizure mutant seizure (sei(ts1)) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB(9ed4) flies was also assessed. Laboratory. Drosophila melanogaster. Sleep deprivation. Sleep deprivation increased seizure susceptibility in adult sesB(9ed4)/+ and sei(ts1) mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB(9ed4)/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB(9ed4)/+ became adults. These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity. © 2015 Associated Professional Sleep Societies, LLC.

Orgasm Induced Seizures: A Rare Phenomenon

African Journals Online (AJOL)

testing of the brain revealed no structural abnormality. His blood examination findings were ... A variety of stimuli can cause reflex seizures, Some triggers include light, music and cognitive phenomenon. There are case reports ... seizures cause great personal distress and significantly affect marital relationships. Though ...

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

Science.gov (United States)

Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

MMB4 DMS nanoparticle suspension formulation with enhanced stability for the treatment of nerve agent intoxication.

Science.gov (United States)

Dixon, Hong; Clark, Andrew P-Z; Cabell, Larry A; McDonough, Joe A

2013-01-01

Various oximes are currently fielded or under investigation in the United States and other countries as a component of autoinjector emergency treatment systems for organophosphate nerve agent chemical weapons. Bis-pyridinium oximes in general have greater efficacy against a broad spectrum of nerve agents, but they have poor stability due to hydrolytic degradation at elevated temperatures. 1,1'-Methylenebis-4-[(hydroxyimino)methyl]pyridinium dimethanesulfonate (MMB4 DMS) is a leading candidate for next-generation nerve agent treatment systems, because it is more stable than other bis-pyridinium oximes, but it still degrades quickly at temperatures often encountered during storage and field use. The primary goal is to increase the stability and shelf life of MMB4 while maintaining the desirable pharmacokinetic (PK) properties of the aqueous formulation. We have developed a formulation to be used in a phase 1 clinical trial consisting of MMB4 micro/nanoparticles suspended in cottonseed oil, a biocompatible vegetable oil. Through various milling techniques, the average particle size can be controlled from approximately 200 to 6000 nm to produce non-Newtonian formulations that are viscous enough to resist rapid particle sedimentation while remaining injectable at a range of concentrations from 5 to 400 mg/mL. The preliminary accelerated stability test shows that MMB4 in these formulations is stable for at least 2 years at temperatures up to 80°C. Preliminary preclinical in vivo studies have demonstrated that all concentrations and particle sizes have desirable PK properties, including high bioavailability and rapid absorption, which is critical to combat potent and fast-acting nerve agents.

RSDL decontamination of human skin contaminated with the nerve agent VX.

Science.gov (United States)

Thors, L; Lindberg, S; Johansson, S; Koch, B; Koch, M; Hägglund, L; Bucht, A

2017-03-05

Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31 P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL

Decreased sensitivity to nicotine-induced seizures as a consequence of nicotine pretreatment in long-sleep and short-sleep mice.

Science.gov (United States)

de Fiebre, C M; Collins, A C

1988-01-01

Male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with a subseizure-producing dose of nicotine (2.0 mg/kg) 7.5, 15 and 30 minutes prior to challenge with seizure-producing doses of this drug. Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals. The latency to seizure following nicotine challenge was greater in nicotine pretreated animals than in saline controls. Nicotine pretreated LS mice show a greater decrease in nicotine-induced seizure susceptibility than do nicotine pretreated SS mice. This decrease in seizure susceptibility is consistent with induction of nicotinic receptor desensitization via nicotine pretreatment. It is hypothesized that LS and SS mice might differ in sensitivity to nicotine in part because they differ in baseline levels of desensitized versus functional nicotinic receptors.

Prevention of hyperthermia-induced seizures in immature rats by a hydantoin derivative of naloxone.

Science.gov (United States)

Chatterjie, N; Laorden, M L; Puig, M M; Alexander, G J

1989-01-01

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Axotomy induces MHC class I antigen expression on rat nerve cells

DEFF Research Database (Denmark)

Maehlen, J; Schröder, H D; Klareskog, L

1988-01-01

Immunomorphological staining demonstrates that class I major histocompatibility complex (MHC)-coded antigen expression can be selectively induced on otherwise class I-negative rat nerve cells by peripheral axotomy. Induction of class I as well as class II antigen expression was simultaneously seen...... on non-neural cells in the immediate vicinity of the injured nerve cells. As nerve regeneration after axotomy includes growth of new nerve cell processes and formation of new nerve cell contacts, the present findings raise the question of a role for MHC-coded molecules in cell-cell interactions during...... nerve cell growth....

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

Science.gov (United States)

2016-01-01

Myers AC, Kajekar R, Undem BJ. Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways. Am J...induced neuro- peptide production in rapidly adapting afferent nerves in guinea pig airways. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L775–L781...co-localization of transient receptor po- tential vanilloid (trpv)1 and sensory neuropeptides in the guinea - pig respiratory system. Neuroscience

Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

Science.gov (United States)

Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

2012-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.

Science.gov (United States)

Renault, Marie-Ange; Chapouly, Candice; Yao, Qinyu; Larrieu-Lahargue, Frédéric; Vandierdonck, Soizic; Reynaud, Annabel; Petit, Myriam; Jaspard-Vinassa, Béatrice; Belloc, Isabelle; Traiffort, Elisabeth; Ruat, Martial; Duplàa, Cécile; Couffinhal, Thierry; Desgranges, Claude; Gadeau, Alain-Pierre

2013-03-01

Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle. This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.

Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation

Directory of Open Access Journals (Sweden)

do Nascimento-Elias Adriana Helena

2012-08-01

Full Text Available Abstract Background Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco’s modified Eagle’s medium can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Results Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. Conclusions In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.

Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation.

Science.gov (United States)

do Nascimento-Elias, Adriana Helena; Fresnesdas, Bruno César; Schiavoni, Maria Cristina Lopes; de Almeida, Natália Fernanda Gaspar; Santos, Ana Paula; de Oliveira Ramos, Jean; Junior, Wilson Marques; Barreira, Amilton Antunes

2012-08-14

Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco's modified Eagle's medium) can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM) and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.

Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

DEFF Research Database (Denmark)

Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...... and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of Y2 receptors (alone or in combination with neuropeptide Y) could be an alternative strategy for epilepsy treatment....

Alteration of pentylenetetrazole-induced seizure threshold by chronic administration of ginger (Zingiber officinale) extract in male mice.

Science.gov (United States)

Hosseini, Abdolkarim; Mirazi, Naser

2015-05-01

Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in traditional Chinese medicine, has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100 mg/kg) were administered intraperitonal (i.p.), daily for 1 week before induction of PTZ. Phenobarbital sodium (30 mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was recorded. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100 mg/kg (55.33 ± 1.91 versus 24.47 ± 1.33 mg/kg, p < 0.001) and significantly prevented generalized clonic (74.64 ± 3.52 versus 47.72 ± 2.31 mg/kg, p < 0.001) and increased the threshold for the forelimb tonic extension (102.6 ± 5.39 versus 71.82 ± 7.82 mg/kg, p < 0.01) seizure induced by PTZ compared with the control group. Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative stress inhibition.

Polymeric Sorbent with Controlled Surface Polarity: An Alternate for Solid-Phase Extraction of Nerve Agents and Their Markers from Organic Matrix.

Science.gov (United States)

Roy, Kanchan Sinha; Purohit, Ajay Kumar; Chandra, Buddhadeb; Goud, D Raghavender; Pardasani, Deepak; Dubey, Devendra Kumar

2018-06-05

Extraction and identification of lethal nerve agents and their markers in complex organic background have a prime importance from the forensic and verification viewpoint of the Chemical Weapons Convention (CWC). Liquid-liquid extraction with acetonitrile and commercially available solid phase silica cartridges are extensively used for this purpose. Silica cartridges exhibit limited applicability for relatively polar analytes, and acetonitrile extraction shows limited efficacy toward relatively nonpolar analytes. The present study describes the synthesis of polymeric sorbents with tunable surface polarity, their application as a solid-phase extraction (SPE) material against nerve agents and their polar as well as nonpolar markers from nonpolar organic matrices. In comparison with the acetonitrile extraction and commercial silica cartridges, the new sorbent showed better extraction efficiency toward analytes of varying polarity. The extraction parameters were optimized for the proposed method, which included ethyl acetate as an extraction solvent and n-hexane as a washing solvent. Under optimized conditions, method linearity ranged from 0.10 to 10 μg mL -1 ( r 2 = 0.9327-0.9988) for organophosphorus esters and 0.05-20 μg mL -1 ( r 2 = 0.9976-0.9991) for nerve agents. Limits of detection (S:N = 3:1) in the SIM mode were found in the range of 0.03-0.075 μg mL -1 for organophosphorus esters and 0.015-0.025 μg mL -1 for nerve agents. Limits of quantification (S:N = 10:1) were found in the range of 0.100-0.25 μg mL -1 for organophosphorus esters and 0.05-0.100 μg mL -1 for nerve agents in the SIM mode. The recoveries of the nerve agents and their markers ranged from 90.0 to 98.0% and 75.0 to 95.0% respectively. The repeatability and reproducibility (with relative standard deviations (RSDs) %) for organophosphorus esters were found in the range of 1.35-8.61% and 2.30-9.25% respectively. For nerve agents, the repeatability range from 1.00 to 7.75% and reproducibility

Radiation-induced cranial nerve palsy and its causative factors in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Kong Lin; Zhang Youwang; Wu Yongru; Guo Xiaomao; Li Longgen

2005-01-01

Objective: To analyze the incidence and causative factors of radiation-induced cranial nerve palsy in patients with nasopharyngeal carcinoma (NPC). Methods: 512 NPC patients who underwent radiotherapy from January 1, 1989 to December 31, 1990 and from January 1, 1994 to December 31, 1995 were retrospectively analyzed. According to Fuzhou' 92 NPC Staging Classification, there are 31 patients in stage I, 212 in stage II, 198 in stage III and 71 in stage IV. All patients were treated by 60 Co or 6 MV X-ray with faciocervical fields or pre-auricular fields to primary area. Some patients were boosted by post-auricular fields or cranial fields. The median dose to the nasopharyngeal region was 7130 cGy by external beam radiotherapy. Thirty-four patients were boosted by brachytherapy. The medial dose to cervical lymph nodes was 6410 cGy as definitive treatment and 5480 cGy as prophylactic treatment. 101 patients were treated with combined chemotherapy. Results: The median follow-up was 6.7 years . Radiation-induced cranial nerve palsies occurred in 81 among the 512 patients. The 5- and 10-year cumulative incidences were 10.3%, 25.4%, respectively. The most common affected nerve was XII. On multivariates analysis, cranial nerve invasion before radiation, chemotherapy, dose to the nasopharyngeal region and age were the independent factors of radiation-induced cranial nerve palsy on nerve I-VII, while the N stage and the radiation fields were independent factors on nerve IX-XII. The cumulative incidence of cranial nerve I-VII palsies increased in patients with cranial nerve invasion, chemotherapy and the dose to the nasopharyngeal region (>7000 cGy). The cumulative incidence of cranial nerve IX- XII palsies increased in patients with advanced N stage. Patients in the first group of treatment field had the highest risk to progress cranial nerve IX-XII palsies, followed by the second group, and the third group had the lowest risk. Only 1 in 34 patients with brachytherapy

BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. 1. POTENTIOMETRIC ENZYME ELECTRODE. (R823663)

Science.gov (United States)

A potentiometric enzyme electrode for the direct measurement of organophosphate (OP)nerve agents was developed. The basic element of this enzyme electrode was a pH electrodemodified with an immobilized organophosphorus hydrolase (OPH) layer formed by cross-linkingOPH ...

Endodontic periapical lesion-induced mental nerve paresthesia

Science.gov (United States)

Shadmehr, Elham; Shekarchizade, Neda

2015-01-01

Paresthesia is a burning or prickling sensation or partial numbness, resulting from neural injury. The symptoms can vary from mild neurosensory dysfunction to total loss of sensation in the innervated area. Only a few cases have described apical periodontitis to be the etiological factor of impaired sensation in the area innervated by the inferior alveolar and mental nerves. The aim of the present paper is to report a case of periapical lesion-induced paresthesia in the innervation area of the mental nerve, which was successfully treated with endodontic retreatment. PMID:25878687

Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

Science.gov (United States)

Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

2016-07-01

The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

Seizure prognosis of patients with low-grade tumors.

Science.gov (United States)

Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

2012-09-01

Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

Combined Diazepam and MK-801 Therapy Provides Synergistic Protection from Tetramethylenedisulfotetramine-induced Tonic-Clonic Seizures and Lethality in Mice

Science.gov (United States)

Shakarjian, Michael P.; Ali, Mahil S.; Velíšková, Jana; Stanton, Patric K.; Heck, Diane E.; Velíšek, Libor

2015-01-01

The synthetic rodenticide, tetramethylenedisulfotetramine (TMDT), is a persistent and highly lethal GABA-gated Cl− channel blocker. TMDT is clandestinely produced, remains popular in mainland China, and causes numerous unintentional and deliberate poisonings worldwide. TMDT is odorless, tasteless, and easy to manufacture, features that make it a potential weapon of terrorism. There is no effective treatment. We previously characterized the effects of TMDT in C57BL/6 mice and surveyed efficacies of GABAergic and glutamatergic anticonvulsant treatments. At 0.4 mg/kg i.p., TMDT produced neurotoxic symptomatology consisting of twitches, clonic and tonic-clonic seizures, often progressing to status epilepticus and death. If administered immediately after the occurrence of the first clonic seizure, the benzodiazepine diazepam (DZP) effectively prevented all subsequent seizure symptoms, whereas the NMDA receptor antagonist dizocilpine (MK-801) primarily prevented tonic-clonic seizures. The latter agent, however, appeared to be more effective at preventing delayed death. The present study further explored these phenomena, and characterized the therapeutic actions of DZP and MK-801 as combinations. Joint treatment with both DZP and MK-801 displayed synergistic protection against tonic-clonic seizures and 24 hour lethality as determined by isobolographic analysis. Clonic seizures, however, remained poorly controlled. A modification of the treatment regimen, where DZP was followed 10 min later by MK-801, yielded a reduction in both types of seizures and improved overall outcome. Simultaneous monitoring of subjects via EEG and videography confirmed effectiveness of this sequential regimen. We conclude that TMDT blockage at GABAA receptors involves early activation of NMDA receptors, which contribute to persistent ictogenic activity. Our data predict that a sequential combination treatment with DZP followed by MK-801 will be superior to either individual therapy with, or

Nerve Agent Induced Status Epilepticus: From Seizure Onset to Long Lasting Pathology

Science.gov (United States)

2014-01-31

enhancement of glutamatergic and GABAergic synaptic transmission in the mouse amygdala. J Neurophysiol 86:463-74 30. Barik J, Wonnacott S. 2006...reduces neurodegeneration in the amygdala but not in the hippocampus during epileptogenesis. Amino Acids 38: 189-97 235. Quarta D, Naylor CG, Barik

Optogenetic control of thalamus as a tool for interrupting penicillin induced seizures.

Science.gov (United States)

Han, Yechao; Ma, Feiqiang; Li, Hongbao; Wang, Yueming; Xu, Kedi

2015-01-01

Penicillin epilepsy model, whose discharge resembles that of human absence epilepsy, is one of the most useful acute experimental epilepsy models. Though closed-loop optogenetic strategy of interrupting seizures was proved sufficient to switch off epilepsy by controlling thalamus in the post-lesion partial chronic epilepsy model, doubts still exist in absence epilepsy attenuation through silencing thalamus. Here we directly arrested the thalamus to modulate penicillin-induced absence seizures through pseudorandom responsive stimulation on eNpHR-transfected rats. Our data suggested that the duration of epileptiform bursts under light conditions, compared with no light conditions, did not increase or decrease when modulated specific eNpHR-expressing neurons in thalamus.

Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

Science.gov (United States)

Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

2015-08-01

The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

Science.gov (United States)

Besio, W G; Makeyev, O; Medvedev, A; Gale, K

2013-07-01

To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Relationship Between the Dose-Response Curves for Lethality and Severe Effects for Chemical Warfare Nerve Agents

National Research Council Canada - National Science Library

Sommerville, Douglas R

2005-01-01

... (involving acute inhalation exposures to G-type nerve agents) were reviewed and analyzed. For all three studies, slightly more than one standard deviation separated an effective concentration (ECxx...

Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory.

Directory of Open Access Journals (Sweden)

Fraser T Sparks

Full Text Available Damage to the hippocampus (HPC using the excitotoxin N-methyl-D-aspartate (NMDA can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX, a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours or remote (5 weeks time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.

Methadone-induced Torsades de Pointes Masquerading as Seizures

Directory of Open Access Journals (Sweden)

David C. Traficante

2017-01-01

Full Text Available The authors herein present the case of a 53-year-old female who was being treated as an outpatient for seizure disorder but was also receiving high-dose methadone therapy. She presented to the emergency department (ED for what appeared to be a seizure and was found to have a prolonged QT interval, as well as runs of paroxysmal polymorphic ventricular tachycardia with seizure-like activity occurring during the arrhythmia. The markedly prolonged QT interval corrected after treatment with intravenous magnesium; subsequent electroencephalogram, neurology and cardiology consultations confirmed the cause of the recurrent seizure-like episodes to be secondary to the cardiotoxic effects of methadone.

Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine

Directory of Open Access Journals (Sweden)

Rivelilson Mendes de Freitas

2011-06-01

Full Text Available The aim of this study was to evaluate the in vitro antioxidant effects of 12-[(2R,5R,6R-5-hydroxy-6-methylpiperidin-2-yl]dodecan-2-one (iso-6-cassine; ISO and the anticonvulsant effects of ISO on pilocarpine-induced seizures in rats. Wistar rats were treated with 0.9% saline (i.p., control group, pilocarpine (400 mg/kg, i.p., pilocarpine group, and the association of ISO (1.0 mg/kg, i.p. plus pilocarpine (400 mg/kg, i.p., 30 min after administration of ISO (ISO plus pilocarpine group. After the treatments all groups were observed for 1h. The antioxidant effect of ISO on the pilocarpine model was assessed by determining the activity of glutathione peroxidase (GPx, glutathione-S-transferase (GST and catalase (CAT as well as the levels of reactive species (RS and lipid peroxidation (LP. In vitro, ISO (5 μM reduced RS and LP. ISO (1.0 mg/kg and abolished seizures and death induced by pilocarpine in rats. ISO protected against the increase in the RS and LP levels, GST activity as well as the inhibition of GPx activity caused by pilocarpine. In addition, ISO increased the catalase activity in hippocampus of seized rats. In conclusion, the dta suggest that ISO can present anticonvulsant and antioxidant properties in the pilocarpine model of seizures in rats.

An analysis of quality of life (QOL) in patients with epilepsy and comorbid psychogenic nonepileptic seizures (PNES) after vagus nerve stimulation (VNS).

Science.gov (United States)

Vivas, Andrew C; Reitano, Christian J; Waseem, Hena; Benbadis, Selim R; Vale, Fernando L

2017-08-01

Patients with epilepsy (PWE) may suffer from comorbid psychogenic nonepileptic seizures (PNES). The efficacy of vagus nerve stimulation (VNS) in the treatment of epilepsy and depression is established, however the impact on PNES is unknown. Since many patients with PNES have comorbid depression, we explored the impact on quality of life (QOL) that VNS has on PWE and PNES. The video electroencephalogram (vEEG) of all patients who underwent VNS at our institution was reviewed. Patients diagnosed with both psychogenic seizures and epileptic seizures on their vEEG were included in this study. These patients were contacted, and given a QOLIE-31 survey to assess their quality of life after VNS. Patients also completed a separate survey created by our group to categorize the quartile of their improvement. Pre-operative psychiatric disease was retrospectively reviewed. From a period of 2001 to 2016, 518 patients underwent placement of VNS for drug resistant epilepsy (DRE) at our institution. In total, 16 patients were diagnosed with both epilepsy and PNES. 11/16 patients responded to our questionnaire and survey. 9 out of 11 patients felt that their epileptic seizures had improved after VNS, while 7 of the 11 patients felt that their psychogenic episodes had improved. 2(28.6%), 1 (14.3%), and 4 (57.1%) of participants said their PNES improved by 25-50%, 50-75%, and 75-100%, respectively. 3(27.3%), 3 (27.3%), 1 (9.1%), and 4 (36.4%) of the participants said their epileptic seizures improved by 0-25%, 25-50%, 50-75%, and 75-100%, respectively. The average overall score for quality of life for the study participants was found to be 51 (±8) out of 100. Patients with epilepsy and comorbid PNES may benefit from VNS. It is unclear whether the benefit is conferred strictly from decreased epileptic seizure burden. The possible effect on PNES may be related to the known effect of VNS on depression. Further studies are necessary to elucidate the role of VNS in the treatment of PNES

Down-Regulation of Homer1b/c Protects Against Chemically Induced Seizures Through Inhibition of mTOR Signaling

Directory of Open Access Journals (Sweden)

Lei Cao

2015-03-01

Full Text Available Background: Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. Reducing Homer1b/c expression has been shown in previous studies to be protective against excitotoxic insults, implicating Homer1b/c in the physiological regulation of aberrant neuronal excitability. Methods: To test the efficacy of a Homer1b/c reducing therapy for disorders with a detrimental hyperexcitability profile in mice, we used small interfere RNA (siRNA to decrease endogenous Homer1b/c expression in mouse hippocampus. The baseline motor and cognitive behavior was measured by sensorimotor tests, Morris water maze and elevated plus maze tasks. The anti-epileptic effects of Homer1b/c knockdown were determined in two chemically induced seizure models induced by Picrotoxin (PTX or pentylenetetrazole (PTZ administration. Results: The results of sensorimotor tests, Morris water maze and elevated plus maze tasks showed that Homer1b/c reduction had no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced Homerb/c protein had less severe seizures than control mice. Total Homer1b/c protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of Homer1b/c. In addition, the phosphorylation of mammalian target of rapamycin (mTOR and its target protein S6 was significantly inhibited in Homer1b/c down-regulated mice. Homer1b/c knockdown-induced inhibition of mTOR pathway was partially ablated by the metabotropic glutamate receptor 5 (mGluR5 agonist CHPG. Conclusion: Our results demonstrate that endogenous Homer1b/c is integral for regulating neuronal hyperexcitability in adult animals and suggest that reduction of Homer1b/c could protect against chemically induced seizures through inhibition mTOR pathway.

Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP

DEFF Research Database (Denmark)

Sørensen, Andreas T; Nikitidou, Litsa; Ledri, Marco

2009-01-01

(TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY...... is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected...... injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP...

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity.

Science.gov (United States)

Kadiyala, Sridhar B; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M; Jayakumar, Sachidhanand; Herron, Bruce J; Ferland, Russell J

2015-01-01

Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2's seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ∼85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype

Seizure tests distinguish intermittent fasting from the ketogenic diet

Science.gov (United States)

Hartman, Adam L.; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J. Marie

2010-01-01

Summary Purpose Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Methods Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ~ 12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. Results The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. Discussion In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. PMID:20477852

Seizure tests distinguish intermittent fasting from the ketogenic diet.

Science.gov (United States)

Hartman, Adam L; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J Marie

2010-08-01

Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3-4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz-induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Sound-induced facial synkinesis following facial nerve paralysis.

Science.gov (United States)

Ma, Ming-San; van der Hoeven, Johannes H; Nicolai, Jean-Philippe A; Meek, Marcel F

2009-08-01

Facial synkinesis (or synkinesia) (FS) occurs frequently after paresis or paralysis of the facial nerve and is in most cases due to aberrant regeneration of (branches of) the facial nerve. Patients suffer from inappropriate and involuntary synchronous facial muscle contractions. Here we describe two cases of sound-induced facial synkinesis (SFS) after facial nerve injury. As far as we know, this phenomenon has not been described in the English literature before. Patient A presented with right hemifacial palsy after lesion of the facial nerve due to skull base fracture. He reported involuntary muscle activity at the right corner of the mouth, specifically on hearing ringing keys. Patient B suffered from left hemifacial palsy following otitis media and developed involuntary muscle contraction in the facial musculature specifically on hearing clapping hands or a trumpet sound. Both patients were evaluated by means of video, audio and EMG analysis. Possible mechanisms in the pathophysiology of SFS are postulated and therapeutic options are discussed.

A Structure-Activity Analysis of the Variation in Oxime Efficacy Against Nerve Agents

Science.gov (United States)

2008-01-01

cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy ...in our study confirmed previous assessments that oxime protection varies drama - tically against different military nerve agents (Aas, 2003; Dawson... therapy ofacutepoisonings inducedbyanti-cholinesterase neuroparalytic substances. In:Monov, A., Dishovsky, C. (Eds.), Medical Aspects of Chemical and

Neuroprotective Mechanisms Activated in Non-seizing Rats Exposed to Sarin

Science.gov (United States)

2015-06-04

after kainic acid-induced seizures. Brain Res. 1424, 1–8. Johnson, E.A., Kan, R.K., 2010. The acute phase response and soman-induced status epilepticus ...2011. Comparison of status epilepticus models induced by pilocarpine and nerve agents – a systematic review of the underlying aetiology and adopted...2007) Nqo2 Loss of Nqo1 and Nqo2 leads to altered intracellular redox status , decreased expression and activation of NF-κB, and altered

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

Science.gov (United States)

Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

2016-03-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Graphene oxide/MnO{sub 2} nanocomposite as destructive adsorbent of nerve-agent simulants in aqueous media

Energy Technology Data Exchange (ETDEWEB)

Šťastný, Martin, E-mail: stastny@iic.cas.cz [Materials Chemistry Department, Institute of Inorganic Chemistry AS CR v.v.i., 25068 Husinec-Řež (Czech Republic); Faculty of the Environment, J.E. Purkyně University in Ústí nad Labem, Králova Výšina 7, 400 96 Ústí nad Labem (Czech Republic); Tolasz, Jakub; Štengl, Václav; Henych, Jiří [Materials Chemistry Department, Institute of Inorganic Chemistry AS CR v.v.i., 25068 Husinec-Řež (Czech Republic); Žižka, David [Faculty of the Environment, J.E. Purkyně University in Ústí nad Labem, Králova Výšina 7, 400 96 Ústí nad Labem (Czech Republic)

2017-08-01

Highlights: • Nanocomposite graphene oxide-birnessite-type MnO{sub 2} was synthesized by thermal hydrolysis. • New destructive sorbent for safe degradation of nerve-agent simulants. • 95% degradation activity for DMMP and TEP. - Abstract: Graphene oxide/MnO{sub 2} nanocomposite was prepared by thermal hydrolysis of potassium permanganate (KMnO{sub 4}) and 2-chloroacetamide aqueous solutions with graphene oxide (GO) suspension. The synthesized samples were characterized by specific surface area (BET) and porosity determination (BJH), X-ray Diffraction (XRD) and high-resolution electron microscopes (HRSEM, HRTEM). These nanocomposites were used in an experimental evaluation of their adsorption activity with nerve agent simulants dimethyl methyl phosphonate (DMMP) and triethyl phosphate (TEP) in aqueous media. The nanocomposites exhibited enhanced adsorptive degradation ability compared to pure manganese oxide (MnO{sub 2}) and GO. The GO amount in the nanocomposites affected their degradation activity substantially. The best adsorption efficiency was observed for samples with moderate GO amount. Three methods were used to observe the mechanism of the nerve-agent simulants deactivation: Gas chromatography with mass spectrometry (GC–MS), High-Performance Liquid Chromatography (HPLC) and in situ Infrared spectroscopy (FTIR). It was shown that the hydrolysis on the surface of prepared nanocomposites yields volatile primary alcohols (methanol and ethanol) as the main hydrolysis products.

Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats

Institute of Scientific and Technical Information of China (English)

ZHANG Li-san; CHEN Jie-fang; CHEN Guan-feng; HU Xing-yue; DING Mei-ping

2013-01-01

Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases.However,whether these drugs can inhibit epileptogenesis remains unclear.This study aimed to investigate the effects of thioperamide,a selective and potent histamine H3 receptor antagonist,on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.Methods Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times,and seizure activity of kindling was recorded for 30 minutes.Control rats were ip injected with saline instead of PTZ.Morris water maze was used to evaluate the spatial memory.Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.Results Intracerebroventricular (icv) injections with thioperamide (10 μg,20 μg) 30 minutes before every PTZ injections,significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages.PTZ-kindling seizures led to the impairment of spatial memory in rats,and thioperamide ameliorated the impairment of spatial learning and memory.Compared to non-kindling rats,there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats,which was reversed by thioperamide.Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats.The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

The lack of effects of zinc and nitric oxide in initial state of pilocarpine-induced seizures.

Science.gov (United States)

Noyan, Behzat; Jensen, Morten Skovgaard; Danscher, Gorm

2007-07-01

In this study we investigated whether intracerebroventricular (i.c.v.) injection of L-NAME (a nitric oxide synthase inhibitor) or CaEDTA (an extracellular zinc chelator) or the combination of the two could affect the initial phase of pilocarpine induced (2 h) seizures. Two groups of rats were used. Animals from both groups were given with i.c.v. injections of either saline (10 microl), L-NAME (150 microg/10 microl), CaEDTA (100 mM/10 microl) or L-NAME and CaEDTA. One group received pilocarpine HCl (380 mg/kg i.p.) the other served as control. Pilocarpine HCl was injected intraperitoneally 10 min later. The behavior of the animals was observed for 2h and the intensity of their seizures was scored. The rats were then sacrificed and their brains were removed and analyzed for zinc ions by using the immersion autometallography and the TSQ fluorescence staining. All the animals which received pilocarpine HCl developed seizures. Despite treatment with L-NAME and/or CaEDTA we found that the latency and the intensity of seizures were similar in both groups investigated. The distribution of stainable zinc ions and the intensity of staining in hippocampus were not affected by pilocarpine and found unchanged after L-NAME and/or CaEDTA injections in both the control animals and the pilocarpine treated animals. The data suggest that the nitric oxide system and zinc ions do not affect pilocarpine-induced seizures in their initial state.

Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

Science.gov (United States)

Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

2011-09-21

Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options

Directory of Open Access Journals (Sweden)

Wang S

2014-10-01

Full Text Available Shelly Wang,1 Aria Fallah2,3 1Department of Neurosurgery, University of Toronto, Toronto, ON, Canada; 2Department of Neurosurgery, Miami Children’s Hospital, Miami, FL, USA; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Abstract: Seizures are clinically significant manifestations associated with 79%–90% of patients with tuberous sclerosis complex. Often occurring within the first year of life in the form of infantile spasms, seizures interfere with neuropsychiatric, social, and cognitive development and carry significant individual and societal consequences. Prompt identification and treatment of seizures is an important focus in the overall management of tuberous sclerosis complex patients. Medical management, either after seizure onset or prophylactically in infants with electroencephalographic abnormalities, is considered first-line therapy. Vigabatrin and adrenocorticotropic hormone have emerged over the past few decades as mainstay pharmacologic modalities. Furthermore, emerging research on mammalian target of rapamycin inhibitors demonstrated promise for the management of seizures and subependymal giant cell astrocytoma. For appropriate surgical candidates with an epileptogenic zone associated with one or more glioneuronal hamartomas, ideally in noneloquent cortex, resective surgery can be considered, which provides a cure in 56% of patients. For medically refractory patients who do not meet criteria for curative surgery, palliative surgical approaches focused on reducing seizure burden, in the form of corpus callosotomy and vagus nerve stimulation, are alternative management options. Lastly, the ketogenic diet, a reemerging therapy based on the anticonvulsant effects of ketone bodies, can be utilized independently or in conjunction with other treatment modalities for the management of difficult-to-treat seizures. Keywords: epilepsy, adrenocorticotropic hormone, vigabatrin, mammalian

Activation of Phosphoinositide Metabolism by Cholinergic Agents.

Science.gov (United States)

1992-03-15

most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

Oxidative stress in immature brain following experimentally-induced seizures

Czech Academy of Sciences Publication Activity Database

Folbergrová, Jaroslava

2013-01-01

Roč. 62, Suppl.1 (2013), S39-S48 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR(CZ) GA309/08/0292; GA ČR(CZ) GAP303/10/0999; GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) LL1204 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : immature rats * experimentally-induced seizures * oxidative stress * mitochondrial dysfunction * antioxidant defense Subject RIV: FH - Neurology Impact factor: 1.487, year: 2013

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

Science.gov (United States)

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-01-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsOrganophosphate Pesticides and Nerve Agents

Energy Technology Data Exchange (ETDEWEB)

Liu, Guodong; Wang, Jun; Barry, Richard C.; Petersen, Catherine E.; Timchalk, Charles; Gassman, Paul L.; Lin, Yuehe

2008-11-01

A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE) adducts, which is a potential exposure biomarker for organophosphate pesticides (OP) and chemical warfare nerve agent exposures. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to track the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemical stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as a model OP insecticide to prepare the phosphorylated AChE adduct to demonstrate the proof of principle for this sensor technology. The paraoxon-AChE adduct was characterized by Fourier Transform Infrared Spectrum, and the binding affinity of anti-AChE to the paraoxon-AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM paraoxon-AChE, and the limit of detection is estimated to be 8 pM. This new nanoparticle-based electrochemical immunosensor thus provides a sensitive and quantitative tool for biomonitoring exposure to OP pesticides and nerve agents.

Effects of Berberis vulgaris fractions on PTZ Induced seizure in male rats

Directory of Open Access Journals (Sweden)

2017-11-01

Full Text Available Background and objectives: Berberis vulgaris L (Berberidaceae is a medicinal plant that is distributed in different parts of Iran; it is grown as a wild or cultivated plant. It has different pharmacological activities such as antioxidant, anti-inflammatory, anti-arrhythmic, sedative and anti-malaria effects. In this study, the anti-seizure activity of different fractions of this plant was evaluated. Methods: Seventy two rats were randomly divided in to nine groups (n=8 in each group. (1: negative control group (normal saline 10mL/kg, (2: positive control group (sodium valproate 1 mg/kg, (3, 4, 5: hydroalcoholic extract-treated groups (100, 200, 400 mg/kg, (6, 7: methanol fraction-treated groups (100 and 200 mg/kg and (8, 9: chloroform fraction-treated group (100 and 200 mg/kg. Thirty minute after peritoneal injection of different doses of extract, fractions, saline and gavage of sodium valproate, PTZ (45 mg/kg was injected and they were immediately transferred to a special cage, and the seizure parameters were evaluated for 30 min. Result: The injection of different doses of hydroalcoholic extract and different fractions had a dose-dependent effect on prolongation of latency to the onset of seizures. The effective dose was 400 mg/kg of hydroalcoholic extract and 200 mg/kg of methanol fraction. They decreased the rate of mortality and the number of suddenly seizures jumping significantly. Conclusion: The present study demonstrated that the hydroalcoholic extract and methanol fraction of B. vulgaris showed anticonvulsant activity in PTZ-induced seizures in mice. Therefore, this plant may be more useful in petit mal epilepsy.

Matrix metalloproteinase-2 is downregulated in sciatic nerve by streptozotocin induced diabetes and/or treatment with minocycline: Implications for nerve regeneration

Science.gov (United States)

Ali, Sumia; Driscoll, Heather E.; Newton, Victoria L.; Gardiner, Natalie J.

2014-01-01

Minocycline is an inhibitor of matrix metalloproteinases (MMPs) and has been shown to have analgesic effects. Whilst increased expression of MMPs is associated with neuropathic pain, MMPs also play crucial roles in Wallerian degeneration and nerve regeneration. In this study we examined the expression of MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1/-2 in the sciatic nerve of control and streptozotocin-induced diabetic rats treated with either vehicle or minocycline by quantitative PCR and gelatin zymography. We assessed the effects of minocycline on nerve conduction velocity and intraepidermal nerve fibre (IENF) deficits in diabetic neuropathy and investigated the effects of minocycline or MMP-2 on neurite outgrowth from primary cultures of dissociated adult rat sensory neurons. We show that MMP-2 is expressed constitutively in the sciatic nerve in vivo and treatment with minocycline or diabetes leads to downregulation of MMP-2 expression and activity. The functional consequence of this is IENF deficits in minocycline-treated nondiabetic rats and an unsupportive microenvironment for regeneration in diabetes. Minocycline reduces levels of MMP-2 mRNA and nerve growth factor-induced neurite outgrowth. Furthermore, in vivo minocycline treatment reduces preconditioning-induced in vitro neurite outgrowth following a sciatic nerve crush. In contrast, the addition of active MMP-2 facilitates neurite outgrowth in the absence of neurotrophic support and pre-treatment of diabetic sciatic nerve substrata with active MMP-2 promotes a permissive environment for neurite outgrowth. In conclusion we suggest that MMP-2 downregulation may contribute to the regenerative deficits in diabetes. Minocycline treatment also downregulates MMP-2 activity and is associated with inhibitory effects on sensory neurons. Thus, caution should be exhibited with its use as the balance between beneficial and detrimental outcomes may be critical in assessing the benefits of using

An Acetylcholinesterase-Based Chronoamperometric Biosensor for Fast and Reliable Assay of Nerve Agents

Directory of Open Access Journals (Sweden)

Rene Kizek

2013-08-01

Full Text Available The enzyme acetylcholinesterase (AChE is an important part of cholinergic nervous system, where it stops neurotransmission by hydrolysis of the neurotransmitter acetylcholine. It is sensitive to inhibition by organophosphate and carbamate insecticides, some Alzheimer disease drugs, secondary metabolites such as aflatoxins and nerve agents used in chemical warfare. When immobilized on a sensor (physico-chemical transducer, it can be used for assay of these inhibitors. In the experiments described herein, an AChE- based electrochemical biosensor using screen printed electrode systems was prepared. The biosensor was used for assay of nerve agents such as sarin, soman, tabun and VX. The limits of detection achieved in a measuring protocol lasting ten minutes were 7.41 × 10−12 mol/L for sarin, 6.31 × 10−12 mol /L for soman, 6.17 × 10−11 mol/L for tabun, and 2.19 × 10−11 mol/L for VX, respectively. The assay was reliable, with minor interferences caused by the organic solvents ethanol, methanol, isopropanol and acetonitrile. Isopropanol was chosen as suitable medium for processing lipophilic samples.

Vagus Nerve Stimulation for Electrographic Status Epilepticus in Slow-Wave Sleep.

Science.gov (United States)

Carosella, Christopher M; Greiner, Hansel M; Byars, Anna W; Arthur, Todd M; Leach, James L; Turner, Michele; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

2016-07-01

Electrographic status epilepticus in slow sleep or continuous spike and waves during slow-wave sleep is an epileptic encephalopathy characterized by seizures, neurocognitive regression, and significant activation of epileptiform discharges during nonrapid eye movement sleep. There is no consensus on the diagnostic criteria and evidence-based optimal treatment algorithm for children with electrographic status epilepticus in slow sleep. We describe a 12-year-old girl with drug-resistant electrographic status epilepticus in slow wave sleep that was successfully treated with vagus nerve stimulation. Her clinical presentation, presurgical evaluation, decision-making, and course after vagus nerve stimulator implantation are described in detail. After vagus nerve stimulator implantation, the girl remained seizure free for more than a year, resolved the electrographic status epilepticus in slow sleep pattern on electroencephalography, and exhibited significant cognitive improvement. Vagus nerve stimulation may be considered for electrographic status epilepticus in slow sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

Managing Lafora body disease with vagal nerve stimulation.

Science.gov (United States)

Mikati, Mohamad A; Tabbara, Faysal

2017-03-01

A 17-year-old female, of consanguineous parents, presented with a history of seizures and cognitive decline since the age of 12 years. She had absence, focal dyscognitive, generalized myoclonic, and generalized tonic-clonic seizures, all of which were drug resistant. The diagnosis of Lafora body disease was made based on a compatible clinical, EEG, seizure semiology picture and a disease-causing homozygous mutation in the EPM2A gene. A vagus nerve stimulator (VNS) was inserted and well tolerated with a steady decrease and then stabilization in seizure frequency during the six months following insertion (months 1-6). At follow-up, at 12 months after VNS insertion, there was a persistent improvement. Seizure frequency during months 7-12, compared to pre-VNS, was documented as follows: the absence seizures observed by the family had decreased from four episodes per month to 0 per month, the focal dyscognitive seizures from 300 episodes per month to 90 per month, the generalized myoclonic seizures from 90 clusters per month to eight per month, and the generalized tonic-clonic seizures from 30 episodes per month to 1.5 per month on average. To our knowledge, this is the second case reported in the literature showing efficacy of VNS in the management of seizures in Lafora body disease.

Neurotoxic effects of methylcyclopentadienyl manganese tricarbonyl (MMT) in the mouse: basis of MMT-induced seizure activity.

Science.gov (United States)

Fishman, B E; McGinley, P A; Gianutsos, G

1987-08-01

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese-containing compound which is used as an additive in unleaded gasoline. One neurotoxic effect of MMT in mice is seizure activity. In this study, seizures were observed in mice treated with MMT in propylene glycol or corn oil. The LD50 associated with seizure activity was lower in mice receiving MMT in propylene glycol (152 mg/kg) than in those receiving MMT in corn oil (999 mg/kg). Manganese concentrations in the brains of mice which showed seizure activity due to MMT were higher than in those that did not (2.45 micrograms/g vs. 1.14 micrograms/g for MMT treated in propylene glycol and 3.25 micrograms/g vs. 1.63 micrograms/g for MMT in corn oil). Mice treated with manganese chloride (MnCl2) showed increases in brain manganese comparable to those of the mice showing seizure activity due to MMT, but exhibited no sign of seizure activity. MMT in non-lethal seizure-inducing doses had no effect on the accumulation of 4-aminobutyric acid (GABA) in mouse brain. However, MMT inhibited the binding of t-[3H]t-butylbicycloorthobenzoate [3H]-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse brain membranes with an IC50 value of 22.8 microM. The data suggest that MMT (organic manganese) or a closely related metabolite and not elemental manganese itself is responsible for the seizure activity observed. The seizure activity may be the result of an inhibitory effect of MMT at the GABA-A receptor linked chloride channel.

Neurotoxic effects of methylcyclopentadienyl manganese tricarbonyl (MMT) in the mouse: basis of MMT-induced seizure activity

International Nuclear Information System (INIS)

Fishman, B.E.; McGinley, P.A.; Gianutsos, Gerald

1987-01-01

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese-containing compound which is used as an additive in unleaded gasoline. One neurotoxic effect of MMT in mice is seizure activity. In this study, seizures were observed in mice treated with MMT in propylene glycol or corn oil. The LD 50 associated with seizure activity was lower in mice receiving MMT in propylene glycol (152 mg/kg) than in those receiving MMT in corn oil (999 mg/kg). Manganese concentrations in the brains of mice which showed seizure activity due to MMT were higher than in those than did not (2.45 μg/g vs, l.14 μg/g for MMT treated in propylene glycol and 3.25 μg/g vs. l.63 μg/g for MMT in corn oil). Mice treated with manganese chloride (MnCl 2 ) showed increases in brain manganese comparable to those of the mice showing seizure activity due to MMT, but exhibited no sign of seizure activity. MMT in non-lethal seizure-inducing doses had no effect on the accumulation of 4-aminobutyric acid (GABA) in mouse brain. However, MMT inhibited the binding of t-[ 3 H] t-butylbicycloorthobenzoate [ 3 H]-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse brain membranes with an IC 50 value of 22.8 μM. The data suggest that MMT (organic manganese) or a closely related metabolite and not elemental manganese itself is responsible for the seizure activity observed. The seizure activity may be the result of an inhibitory effect of MMT at the GABA-A receptor linked chloride channel. 20 refs. (author)

Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

Science.gov (United States)

Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

2017-04-01

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

Evaluation of anticonvulsant and neuroprotective effects of camel milk in strychnine-induced seizure model

Directory of Open Access Journals (Sweden)

Humera Khatoon

2015-10-01

Full Text Available Objective: To discover the use of camel milk as an alternate medicine for the treatment and prevention of convulsions using strychnine-induced seizure model. Methods: Thirty animals were divided into three equal groups. Group I was on distilled water, Group II was on camel milk for 15 days prior to experiment and Group III was on reference drug diazepam. On the day of experiment, strychnine was administered in all treatment groups after distilled water, camel milk and diazepam treatments respectively. Animals were observed for 30 min for latency of seizure onset, frequency of convulsions and duration of jerks. The mortality rate was also evaluated for each group. Results: Camel milk treatment showed significant seizure protection as observed by delayed seizure onset (P ≤ 0.001, decreased total duration of convulsions (P ≤ 0.001 and mortality rate (P ≤ 0.001 when compared with Group I. Conclusions: Anticonvulsant activity of camel milk could be due to potentiation of glycinergic and GABAergic activities both. Antioxidant activity can also amplify its antiepileptic activity. Further studies are required to confirm the exact mechanism of action.

Elimination of zinc-65 from the brain under kainate-induced seizures.

Science.gov (United States)

Takeda, Atsushi; Hirate, Maki; Oku, Naoto

2004-04-01

On the basis of the previous evidence that 65Zn concentrations in the brain of EL (epilepsy) mice was affected by induction of seizures, 65Zn movement in the brain was quantitatively evaluated in ddY mice treated with kainate. Six days after intravenous injection of 65ZnCl2, mice were intraperitoneally injected with kainate (10 mg/kg x 6 times in 2 weeks). Myoclonic jerks were observed during treatment with kainate. Twenty days after 65Zn injection, 65Zn distribution in the brain was compared between the kainite-treated and control mice. 65Zn distribution in the brain of the kainate-treated mice was overall lower than in the control mice. 65Zn concentration was significantly decreased in the frontal cortex, hippocampal CA1, thalamus and hypothalamus by treatment with kainate. These results demonstrate that kainate-induced seizures are linked to decreased zinc concentrations in the brain.

Atomoxetine, a norepinephrine reuptake inhibitor, reduces seizure-induced respiratory arrest.

Science.gov (United States)

Zhang, Honghai; Zhao, Haiting; Feng, Hua-Jun

2017-08-01

Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication, and no effective preventive strategies are currently available for this fatal disorder. Clinical and animal studies of SUDEP demonstrate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death after generalized seizures in many cases. Enhancing brain levels of serotonin reduces S-IRA in animal models relevant to SUDEP, including the DBA/1 mouse. Given that serotonin in the brain plays an important role in modulating respiration and arousal, these findings suggest that deficits in respiration and/or arousal may contribute to S-IRA. It is well known that norepinephrine is an important neurotransmitter that modulates respiration and arousal in the brain as well. Therefore, we hypothesized that enhancing noradrenergic neurotransmission suppresses S-IRA. To test this hypothesis, we examined the effect of atomoxetine, a norepinephrine reuptake inhibitor (NRI), on S-IRA evoked by either acoustic stimulation or pentylenetetrazole in DBA/1 mice. We report the original observation that atomoxetine specifically suppresses S-IRA without altering the susceptibility to seizures evoked by acoustic stimulation, and atomoxetine also reduces S-IRA evoked by pentylenetetrazole in DBA/1 mice. Our data suggest that the noradrenergic signaling is importantly involved in S-IRA, and that atomoxetine, a medication widely used to treat attention deficit hyperactivity disorder (ADHD), is potentially useful to prevent SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

Annual Report 2013-2014: Theoretical Studies of Nerve Agents Adsorbed on Surfaces

Science.gov (United States)

2014-07-08

magnesium oxide. Journal of Physical Chemistry B 2004, 108, 5294-5303. 7. Michalkova, A.; Paukku, Y.; Majumdar, D.; Leszczynski, J., Theoretical study...M.; Hyre, A. M., Ultraviolet Raman Spectra and Cross-Sections of the G-series Nerve Agents. Applied Spectroscopy 2008, 62, 1078-1083. 12. DaBell...mol) 24 2.3 Raman and DFT study of pyrocarbonate 2.3.1 In-situ Raman spectroscopic investigation The Li2CO3 and Na2CO3 eutectic mixture (52:48

Systemic morphine blocks the seizures induced by intracerebroventricular (i.c.v.) injections of opiates and opioid peptides.

Science.gov (United States)

Urca, G; Frenk, H

1982-08-19

Intracerebroventricular (i.c.v.) injections of the endorphins and of morphine in rats produce highly characteristic, naloxone sensitive, electrographic seizures. In contrast, systemic injections of morphine have been shown to exert a marked anticonvulsant effect. The present study demonstrates that systemic morphine pretreatment can prevent the occurrence of electrographic seizures injected by i.c.v. morphine, Leu-enkephalin and beta-endorphin and that the anti-epileptic effect of morphine can be reversed by naloxone. Male albino rats, previously prepared for chronic i.c.v. injections and EEG recordings, were pretreated with 0--100 mg/kg of intraperitoneal (i.p.) morphine. Thirty five minutes later morphine (520 nmol), Leu-enkephalin (80 nmol) or beta-endorphin (5 nmol) were injected i.c.v. Pretreatment with i.p. morphine blocked the occurrence of seizures induced by morphine and both endogenous opioids. Lower doses of systemic morphine (50 mg/kg) were necessary to block i.c.v. morphine seizures than the dose (100 mg/kg) necessary to block seizures induced by i.c.v. Leu-enkephalin and beta-endorphin. Naloxone (1 mg/kg) administered 25 min following 50 mg/kg of i.p. morphine and preceding the injections of i.c.v. morphine reversed the antiepileptic effect of systemic morphine. These results demonstrate the possible existence of two opiate sensitive systems, one with excitatory-epileptogenic effects and the other possessing inhibitory-antiepileptic properties. The possible relationship between these findings and the known heterogeneity of opiate receptors and opiate actions is discussed.

Age-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

Directory of Open Access Journals (Sweden)

Seok Kyu eKang

2015-05-01

Full Text Available Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB, with NKCC1 antagonist bumetanide (BTN as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7, 10 and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

Science.gov (United States)

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Peripheral nerve injury induces glial activation in primary motor cortex

OpenAIRE

Julieta Troncoso; Julieta Troncoso; Efraín Buriticá; Efraín Buriticá

2015-01-01

Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to eithe...

Clustering of spontaneous recurrent seizures separated by long seizure-free periods: An extended video-EEG monitoring study of a pilocarpine mouse model.

Science.gov (United States)

Lim, Jung-Ah; Moon, Jangsup; Kim, Tae-Joon; Jun, Jin-Sun; Park, Byeongsu; Byun, Jung-Ick; Sunwoo, Jun-Sang; Park, Kyung-Il; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Kim, Manho; Jeon, Daejong; Chu, Kon; Lee, Sang Kun

2018-01-01

Seizure clustering is a common and significant phenomenon in patients with epilepsy. The clustering of spontaneous recurrent seizures (SRSs) in animal models of epilepsy, including mouse pilocarpine models, has been reported. However, most studies have analyzed seizures for a short duration after the induction of status epilepticus (SE). In this study, we investigated the detailed characteristics of seizure clustering in the chronic stage of a mouse pilocarpine-induced epilepsy model for an extended duration by continuous 24/7 video-EEG monitoring. A seizure cluster was defined as the occurrence of one or more seizures per day for at least three consecutive days and at least five seizures during the cluster period. We analyzed the cluster duration, seizure-free period, cluster interval, and numbers of seizures within and outside the seizure clusters. The video-EEG monitoring began 84.5±33.7 days after the induction of SE and continued for 53.7±20.4 days. Every mouse displayed seizure clusters, and 97.0% of the seizures occurred within a cluster period. The seizure clusters were followed by long seizure-free periods of 16.3±6.8 days, showing a cyclic pattern. The SRSs also occurred in a grouped pattern within a day. We demonstrate that almost all seizures occur in clusters with a cyclic pattern in the chronic stage of a mouse pilocarpine-induced epilepsy model. The seizure-free periods between clusters were long. These findings should be considered when performing in vivo studies using this animal model. Furthermore, this model might be appropriate for studying the unrevealed mechanism of ictogenesis.

Vagus nerve stimulation and stereotactic radiosurgery

International Nuclear Information System (INIS)

Kawai, Kensuke

2005-01-01

Vagus nerve stimulation and stereotactic radiosurgery represent novel and less invasive therapeutics for medically intractable epilepsy. Chronic stimulation of the left vagus nerve with implanted generator and electrodes inhibits seizure susceptibility of the cerebral cortices. While the underlying mechanisms of the effect remains to be further elucidated, the efficacy and safety of vagus nerve stimulation have been established by randomized clinical trials in the United States and European countries. It has been widely accepted as a treatment option for patients with medically intractable epilepsy and for whom brain surgery is not indicated. The primary indication of vagus nerve stimulation in the clinical trials was localization-related epilepsy in adult patients but efficacy in a wide range of patient groups such as generalized epilepsy and children has been reported. Improvements in daytime alertness, mood, higher cognitive functions and overall quality of life have been reported other than the effect on epileptic seizures. Since the devices are not approved for clinical use in Japan by the Health, Labor and Welfare Ministry, there exist barriers to provide this treatment to patients at present. Stereotactic radiosurgery has been used for temporal lobe epilepsy and hypothalamic hamartoma, but it is still controversial whether the therapy is more effective and less invasive than brain surgery. Promising results of gamma knife radiosurgery for medically intractable temporal lobe epilepsy with unilateral hippocampal sclerosis have been reported essentially from one French center. Results from others were not as favorable. There seems to be an unignorable risk of brain edema and radiation necrosis when the delivered dose over the medial temporal structures is high enough to abolish epileptic seizures. A randomized clinical trial comparing different marginal doses is ongoing in the United States. Clinical trials like this, technical advancement and standardization

Sex and Hormonal influences on Seizures and Epilepsy

Science.gov (United States)

Velíšková, Jana; DeSantis, Kara A.

2012-01-01

Epilepsy is the third most common chronic neurological disorder. Clinical and experimental evidence supports the role of sex and influence of sex hormones on seizures and epilepsy as well as alterations of the endocrine system and levels of sex hormones by epileptiform activity. Conversely, seizures are sensitive to changes in sex hormone levels, which in turn may affect the seizure-induced neuronal damage. The effects of reproductive hormones on neuronal excitability and seizure-induced damage are complex to contradictory and depend on different mechanisms, which have to be accounted for in data interpretation. Both estradiol and progesterone/allopregnanolone may have beneficial effects for patients with epilepsy. Individualized hormonal therapy should be considered as adjunctive treatment in patients with epilepsy to improve seizure control as well as quality of life. PMID:22504305

The Use of Adenosine Agonists to Treat Nerve Agent-Induced Seizure and Neuropathology

Science.gov (United States)

2016-09-01

not be cited for purposes of advertisement . REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this...survivability. That was an important step to clinical relevancy as it was feared that ADO’s depression of cardiovascular output would exacerbate...kainate, adenosine and neuropeptide Y receptors. Neurochemical Research. 28: 1501-1515. 23. Bjorness, T. E. & R. W. Greene . 2009. Adenosine and sleep

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

Science.gov (United States)

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-07-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

Science.gov (United States)

Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

2016-01-01

The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

Multiple Cranial Nerve Palsy Due to Cerebral Venous Thrombosis

Directory of Open Access Journals (Sweden)

Esra Eruyar

2017-04-01

Full Text Available Cerebral venous thrombosis (CVT is a rare clinical condition between cerebrovasculer diases. The most common findings are headache, seizure and focal neurological deficit. Multiple cranial nerve palsy due to CVT is rarely seen and it is not clear pathology. A pathology that could explain the lack of cranial nerve imaging is carrying suspected diagnosis but the disease is known to provide early diagnosis and treatment. We want to emphasize with this case multipl cranial nerve palsy due to CVT is seen rarely and good response to treatment.

Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition.

Science.gov (United States)

Gersner, R; Ekstein, D; Dhamne, S C; Schachter, S C; Rotenberg, A

2015-11-01

Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model

A Case of Habitual Neck Compression Induced Electroencephalogram Abnormalities: Differentiating from Epileptic Seizures Using a Tc-99m HMPAO SPECT

Energy Technology Data Exchange (ETDEWEB)

Choi, Hongyoon; Seo, Minseok; Lee, Hoyoung; Kim, Youngsoo; Yun, Changho; Kim, Sangeun; Park, Sungho [Seoul National Univ. Bundang Hospital, Seongnam (Korea, Republic of)

2014-06-15

Self-induced hypoxia has been reported particularly in adolescents, and it can result in neurological injury. Here, we present a case of electroencephalogram (EEG) abnormalities induced by habitual neck compression differentiated from epileptic seizures by Tc-99m HMPAO SPECT. A 19-year-old male was admitted for evaluation of recurrent generalized tonic-clonic seizures. No interictal EEG abnormality was detected; however, abnormal slow delta waves were found immediately after habitual right neck compression. To differentiate EEG abnormalities due to a hemodynamic deficit induced by habitual neck compression from an epileptic seizure, Tc-99m HMPAO SPECT was performed immediately after right carotid artery compression. Abnormal delta waves were triggered, and cerebral hypoperfusion in the right internal carotid artery territory was detected on Tc-99m HMPAO SPECT. The slow delta wave detected on the EEG resulted from the cerebral hypoperfusion because of the habitual neck compression.

A Case of Habitual Neck Compression Induced Electroencephalogram Abnormalities: Differentiating from Epileptic Seizures Using a Tc-99m HMPAO SPECT

International Nuclear Information System (INIS)

Choi, Hongyoon; Seo, Minseok; Lee, Hoyoung; Kim, Youngsoo; Yun, Changho; Kim, Sangeun; Park, Sungho

2014-01-01

Self-induced hypoxia has been reported particularly in adolescents, and it can result in neurological injury. Here, we present a case of electroencephalogram (EEG) abnormalities induced by habitual neck compression differentiated from epileptic seizures by Tc-99m HMPAO SPECT. A 19-year-old male was admitted for evaluation of recurrent generalized tonic-clonic seizures. No interictal EEG abnormality was detected; however, abnormal slow delta waves were found immediately after habitual right neck compression. To differentiate EEG abnormalities due to a hemodynamic deficit induced by habitual neck compression from an epileptic seizure, Tc-99m HMPAO SPECT was performed immediately after right carotid artery compression. Abnormal delta waves were triggered, and cerebral hypoperfusion in the right internal carotid artery territory was detected on Tc-99m HMPAO SPECT. The slow delta wave detected on the EEG resulted from the cerebral hypoperfusion because of the habitual neck compression

Peri-optic nerve infiltration during leukaemic relapse: MRI diagnosis

Energy Technology Data Exchange (ETDEWEB)

Madani, A.; Christophe, C. [Department of Imaging, Hopital Universitaire des Enfants Reine Fabiola, Brussels (Belgium); Ferster, A.; Dan, B. [Department of Paediatrics, Hopital Universitaire des Enfants Reine Fabiola, Brussels (Belgium)

2000-01-01

Background. A 10-year-old boy with a history of acute lymphoblastic leukaemia (ALL), but without previous evidence of central nervous system involvement, presented with seizures 3 years after complete remission. Materials and methods. MRI showed bilateral enlargement of the optic nerves despite normal ophthalmological examination. Results. Only the third cerebrospinal fluid examination showed 2 % blasts without concomitant bone-marrow infiltration. Enlargement of the optic nerves was consistent with bilateral leukaemic peri-optic nerve infiltration. The appearances returned to normal after chemotherapy. Conclusion. The optic nerves are a potential site of relapse in patients with systemic and meningeal ALL, even in the absence of ophthalmological signs. (orig.)

Longterm effects of cardiac mediastinal nerve cryoablation on neural inducibility of atrial fibrillation in canines.

Science.gov (United States)

Leiria, Tiago Luiz Luz; Glavinovic, Tamara; Armour, J Andrew; Cardinal, René; de Lima, Gustavo Glotz; Kus, Teresa

2011-04-26

In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1-2 months post Cryo; n=7) or late (4 months post Cryo; n=4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P<0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

International Nuclear Information System (INIS)

Nambiar, Madhusoodana P.; Gordon, Richard K.; Rezk, Peter E.; Katos, Alexander M.; Wajda, Nikolai A.; Moran, Theodore S.; Steele, Keith E.; Doctor, Bhupendra P.; Sciuto, Alfred M.

2007-01-01

To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m 3 of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure

Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat.

Science.gov (United States)

Yi, Jung-Sun; Lee, Soon-Keum; Sato, Taka-Aki; Koh, Jae-Young

2003-08-21

Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.

Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy.

Directory of Open Access Journals (Sweden)

Raghav Sundar

Full Text Available Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy.Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample. The mean nerve NDRG1 score was defined by an algorithm based on intensity of staining and percentage of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced neuropathy.111 patients were studied. 17 of 111 (15% developed severe paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in patients with severe neuropathy versus 7.7 in those without severe neuropathy (p = 0.0019. A Receiver operating characteristic (ROC curve analysis of the mean nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013 for the identification of severe neuropathy, with a score of 7 being most discriminative. 13/54 (24% subjects with an NDRG1 score 7 (p = 0.017.Low NDRG1 expression in nerve tissue present within samples of surgical resection may identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve biopsies are not routinely feasible for patients undergoing chemotherapy for early breast cancer, this promising biomarker strategy is compatible with current clinical workflow.

Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

Science.gov (United States)

Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

2015-02-18

Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

AMPEROMETRIC THICK-FILM STRIP ELECTRODES FOR MONITORING ORGANOPHOSPHATE NERVE AGENTS BASED ON IMMOBILIZED ORGANOPHOSPHORUS HYDROLASE. (R823663)

Science.gov (United States)

An amperometric biosensor based on the immobilization of organophosphorus hydrolase(OPH) onto screen-printed carbon electrodes is shown useful for the rapid, sensitive, and low-costdetection of organophosphate (OP) nerve agents. The sensor relies upon the sensitive and ra...

Opiate and non-opiate aspects of morphine induced seizures.

Science.gov (United States)

Frenk, H; Liban, A; Balamuth, R; Urca, G

1982-12-16

The intraperitoneal administration of morphine hydrochloride at doses of 300 mg/kg produced analgesia, catalepsy, and electrographic spiking in rats that developed into electrographic seizure patterns after approximately 2.5 h. Whereas naltrexone (12 mg/kg) reversed analgesia and catalepsy, and diminished electrographic spiking, it precipitated electrographic seizure activity similar to that observed following intraperitoneal morphine alone. These seizures were accompanied by behavioral convulsions. No tolerance to these seizures developed with repeated paired administration of morphine and naltrexone or in morphine tolerant rats, but rather potentiation was observed. The epileptogenic effects were found to be potentiated in amygdaloid kindled rats, as well. It was concluded that morphine at these doses activates two different epileptogenic mechanisms, one mediated by opiate receptors, the other not. The possibility of the simultaneous activation of a morphine sensitive anticonvulsant mechanism is discussed.

On the nature of seizure dynamics

Science.gov (United States)

Stacey, William C.; Quilichini, Pascale P.; Ivanov, Anton I.

2014-01-01

Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between ‘normal’ and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical

Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes

Science.gov (United States)

2005-10-01

1 SUBACUTE LOW DOSE NERVE AGENT EXPOSURE CAUSES DNA FRAGMENTATION IN GUINEA PIG LEUKOCYTES. Jitendra R. Dave1, John R. Moffett1, Sally M...DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per...computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA treated guinea pigs as

Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

Directory of Open Access Journals (Sweden)

Melemedjian Ohannes K

2008-03-01

Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

Seizure Induced by Deep Transcranial Magnetic Stimulation in an Adolescent with Depression.

Science.gov (United States)

Cullen, Kathryn R; Jasberg, Suzanne; Nelson, Brent; Klimes-Dougan, Bonnie; Lim, Kelvin O; Croarkin, Paul E

2016-09-01

Deep transcranial magnetic stimulation (TMS) with an H-1 coil was recently approved by the U.S. Food and Drug Administration (U.S. FDA) for treatment-resistant depression (TRD) in adults. Studies assessing the safety and effectiveness of deep TMS in adolescent TRD are lacking. The purpose of this brief report is to provide a case history of an adolescent enrolled in an investigational deep TMS protocol. A case history is described of the first participant of a sham-controlled clinical trial who had a seizure in the course of deep TMS with parameter settings extrapolated from the adult studies that led to US FDA approval (H-1 coil, 120% target stimulation intensity, 18 Hz, 55 trains of 2-second duration, total 1980 pulses). The participant was a 17-year-old unmedicated female, with no significant medical history and no history of seizures or of drug or alcohol use. Brain magnetic resonance imaging showed no structural abnormalities. She initially received sham, which was well tolerated. During active treatment sessions, titration began at 85% of motor threshold (MT) and increased by 5% per day. Her weekly MT measurements were stable. On her first day of 120% MT (8th active treatment), during the 48th train, the participant had a generalized, tonic-clonic seizure that lasted 90 seconds and resolved spontaneously. She had an emergency medicine evaluation and was discharged home without anticonvulsant medications. There were no further seizures reported at a 6-month follow-up. We report a deep TMS-induced generalized tonic-clonic seizure in an adolescent with TRD participating in a clinical trial. Given the demonstrated benefits of deep TMS for adult TRD, research investigating its use in adolescents with TRD is an important area. However, in light of this experience, additional precautions for adolescents should be considered. We propose that further dose-finding investigations are needed to refine adolescent-specific parameters that may be safe and effective for

Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model

Directory of Open Access Journals (Sweden)

Ibrahim Erkutlu

2015-01-01

Full Text Available Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potassium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug injection injury. This study aimed to assess the time-dependent efficacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by penicillin G potassium administration (30 minutes, 8 or 24 hours. The compound muscle action potentials were recorded pre-injury, early post-injury (within 1 hour and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant improvement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury (P < 0.05; at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection.

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

OpenAIRE

Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

2005-01-01

Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that...

Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.

Science.gov (United States)

Kang, Seok Kyu; Markowitz, Geoffrey J; Kim, Shin Tae; Johnston, Michael V; Kadam, Shilpa D

2015-01-01

Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

Peripheral site ligand conjugation to a non-quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase

NARCIS (Netherlands)

Koning, M.C. de; Grol, M. van; Noort, D.

2011-01-01

Commonly employed pyridinium-oxime (charged) reactivators of nerve agent inhibited acetylcholinesterase (AChE) do not readily pass the blood brain barrier (BBB) because of the presence of charge(s). Conversely, non-ionic oxime reactivators often suffer from a lack of reactivating potency due to a

Investigation of assumptions underlying current safety guidelines on EM-induced nerve stimulation

Science.gov (United States)

Neufeld, Esra; Vogiatzis Oikonomidis, Ioannis; Iacono, Maria Ida; Angelone, Leonardo M.; Kainz, Wolfgang; Kuster, Niels

2016-06-01

An intricate network of a variety of nerves is embedded within the complex anatomy of the human body. Although nerves are shielded from unwanted excitation, they can still be stimulated by external electromagnetic sources that induce strongly non-uniform field distributions. Current exposure safety standards designed to limit unwanted nerve stimulation are based on a series of explicit and implicit assumptions and simplifications. This paper demonstrates the applicability of functionalized anatomical phantoms with integrated coupled electromagnetic and neuronal dynamics solvers for investigating the impact of magnetic resonance exposure on nerve excitation within the full complexity of the human anatomy. The impact of neuronal dynamics models, temperature and local hot-spots, nerve trajectory and potential smoothing, anatomical inhomogeneity, and pulse duration on nerve stimulation was evaluated. As a result, multiple assumptions underlying current safety standards are questioned. It is demonstrated that coupled EM-neuronal dynamics modeling involving realistic anatomies is valuable to establish conservative safety criteria.

Neonatal Seizure Models to Study Epileptogenesis

Directory of Open Access Journals (Sweden)

Yuka Kasahara

2018-04-01

Full Text Available Current therapeutic strategies for epilepsy include anti-epileptic drugs and surgical treatments that are mainly focused on the suppression of existing seizures rather than the occurrence of the first spontaneous seizure. These symptomatic treatments help a certain proportion of patients, but these strategies are not intended to clarify the cellular and molecular mechanisms underlying the primary process of epilepsy development, i.e., epileptogenesis. Epileptogenic changes include reorganization of neural and glial circuits, resulting in the formation of an epileptogenic focus. To achieve the goal of developing “anti-epileptogenic” drugs, we need to clarify the step-by-step mechanisms underlying epileptogenesis for patients whose seizures are not controllable with existing “anti-epileptic” drugs. Epileptogenesis has been studied using animal models of neonatal seizures because such models are useful for studying the latent period before the occurrence of spontaneous seizures and the lowering of the seizure threshold. Further, neonatal seizure models are generally easy to handle and can be applied for in vitro studies because cells in the neonatal brain are suitable for culture. Here, we review two animal models of neonatal seizures for studying epileptogenesis and discuss their features, specifically focusing on hypoxia-ischemia (HI-induced seizures and febrile seizures (FSs. Studying these models will contribute to identifying the potential therapeutic targets and biomarkers of epileptogenesis.

Seizures

Science.gov (United States)

Secondary seizures; Reactive seizures; Seizure - secondary; Seizure - reactive; Convulsions ... or kidney failure Very high blood pressure ( malignant hypertension ) Venomous bites and stings ( snake bite ) Withdrawal from ...

Evaluation of anticonvulsant actions of dibromophenyl enaminones using in vitro and in vivo seizure models.

Directory of Open Access Journals (Sweden)

Mohamed G Qaddoumi

Full Text Available Epilepsy and other seizure disorders are not adequately managed with currently available drugs. We recently synthesized a series of dibromophenyl enaminones and demonstrated that AK6 and E249 were equipotent to previous analogs but more efficacious in suppressing neuronal excitation. Here we examined the actions of these lead compounds on in vitro and in vivo seizure models. In vitro seizures were induced in the hippocampal slice chemically (zero Mg2+ buffer and picrotoxin and electrically using patterned high frequency stimulation (HFS of afferents. In vivo seizures were induced in rats using the 6 Hz and the maximal electroshock models. AK6 (10 µM and E249 (10 µM depressed the amplitude of population spikes recorded in area CA1 of the hippocampus by -50.5±4.3% and -40.1±3.1% respectively, with partial recovery after washout. In the zero Mg2+ model, AK6 (10 µM depressed multiple population spiking (mPS by -59.3±6.9% and spontaneous bursts (SBs by -65.9±7.2% and in the picrotoxin-model by -43.3±7.2% and -50.0±8.3%, respectively. Likewise, E249 (10 µM depressed the zero-Mg2+-induced mPS by -48.8±9.5% and SBs by -55.8±15.5%, and in the picrotoxin model by -37.1±5.5% and -56.5±11.4%, respectively. They both suppressed post-HFS induced afterdischarges and SBs. AK6 and E249 dose-dependently protected rats in maximal electroshock and 6 Hz models of in vivo seizures after 30 min pretreatment. Their level of protection in both models was similar to that obtained with phenytoin Finally, while AK6 had no effect on locomotion in rats, phenytoin significantly decreased locomotion. AK6 and E249, suppressed in vitro and in vivo seizures to a similar extent. Their in vivo activities are comparable with but not superior to phenytoin. The most efficacious, AK6 produced no locomotor suppression while phenytoin did. Thus, AK6 and E249 may be excellent candidates for further investigation as potential agents for the treatment of epilepsy syndromes

An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents.

Science.gov (United States)

Rezk, Peter E; Zdenka, Pierre; Sabnekar, Praveena; Kajih, Takwen; Mata, David G; Wrobel, Chester; Cerasoli, Douglas M; Chilukuri, Nageswararao

2015-01-01

In this study, we determined the ability of recombinant human liver prolidase to hydrolyze nerve agents in vitro and its ability to afford protection in vivo in mice. Using adenovirus containing the human liver prolidase gene, the enzyme was over expressed by 200- to 300-fold in mouse liver and purified to homogeneity by affinity and gel filtration chromatography. The purified enzyme hydrolyzed sarin, cyclosarin and soman with varying rates of hydrolysis. The most efficient hydrolysis was with sarin, followed by soman and by cyclosarin {apparent kcat/Km [(1.9 ± 0.3), (1.7 ± 0.2), and (0.45 ± 0.04)] × 10(5 )M(-1 )min(-1), respectively}; VX and tabun were not hydrolyzed by the recombinant enzyme. The enzyme hydrolyzed P (+) isomers faster than the P (-) isomers. The ability of recombinant human liver prolidase to afford 24 hour survival against a cumulative dose of 2 × LD50 of each nerve agent was investigated in mice. Compared to mice injected with a control virus, mice injected with the prolidase expressing virus contained (29 ± 7)-fold higher levels of the enzyme in their blood on day 5. Challenging these mice with two consecutive 1 × LD50 doses of sarin, cyclosarin, and soman resulted in the death of all animals within 5 to 8 min from nerve agent toxicity. In contrast, mice injected with the adenovirus expressing mouse butyrylcholinesterase, an enzyme which is known to afford protection in vivo, survived multiple 1 × LD50 challenges of these nerve agents and displayed no signs of toxicity. These results suggest that, while prolidase can hydrolyze certain G-type nerve agents in vitro, the enzyme does not offer 24 hour protection against a cumulative dose of 2 × LD50 of G-agents in mice in vivo.

Peripheral nerve stimulator-induced electrostimulation at the P6 ...

African Journals Online (AJOL)

2012-12-03

Dec 3, 2012 ... Original Research: Peripheral nerve stimulator-induced electrostimulation. 216. 2013;19(4). South Afr J Anaesth Analg. Introduction. Spinal anaesthesia is often associated with hypotension and bradycardia.1 Strategies to manage post-spinal hypotension include the use of vasopressors or fluids, or a ...

Photogenic partial seizures.

Science.gov (United States)

Hennessy, M J; Binnie, C D

2000-01-01

To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

Enhanced susceptibility to stress and seizures in GAD65 deficient mice.

Science.gov (United States)

Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D; Koh, Sookyong

2018-01-01

Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation.

Differential effects of acute and repeated electrically and chemically induced seizures on ( sup 3 H)Nimodipine and ( sup 125 I)omega-conotoxin GVIA binding in rat brain

Energy Technology Data Exchange (ETDEWEB)

Gleiter, C.H.; Cain, C.J.; Weiss, S.R.; Post, R.M.; Marangos, P.J. (National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (USA))

1989-07-01

({sup 3}H)Nimodipine and high-affinity ({sup 125}I)omega-conotoxin GVIA (CgTX) binding were investigated in membranes from rat cerebral cortex, cerebellum, and hippocampus after electrically and chemically induced seizures. Animals were decapitated 30 min after a single electroconvulsive shock (ECS) or lidocaine-induced seizure and 24 h after the last of 10 once-daily ECS or six once-daily lidocaine-induced seizures. After a single ECS, ({sup 3}H)nimodipine and ({sup 125}I)CgTX binding sites decreased in cerebral cortex (by 10% and 17%, respectively). A downregulation of ({sup 3}H)nimodipine binding sites in hippocampus occurred after single and repeated lidocaine-induced seizures (by 24% and 11%, respectively), whereas ({sup 125}I)CgTX binding remained unaltered. An earlier report on changes in ({sup 3}H)nitrendipine binding after chronic ECS in cortex and hippocampus was not confirmed.

A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions.

Science.gov (United States)

Rosenberg, Yvonne J; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

2015-08-13

Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product.

Use of anticonvulsants as prophylaxis for seizures in patients on clozapine.

Science.gov (United States)

Caetano, Dorgival

2014-02-01

The aim of this study is to conduct a critical review of the literature regarding the use of anticonvulsants in the prophylaxis of clozapine-induced seizures, to examine the relationship of the latter with clozapine daily dose, serum concentration and other factors than dosage that effect clozapine blood concentration, and to make recommendations for the management of clozapine-induced seizures. A systematic review of English-language MEDLINE articles was undertaken. Clozapine-induced seizures may occur at any dose; the risk increases with dose and goes up to 4% at ≥ 600 mg/day. Some authors have advocated that patients on that dose regimen have anticonvulsant added as a primary prophylactic measure. The author discusses the pitfalls of this recommendation and highlights that seizures are better predicted from serum concentration (1300 ng/ml) rather than dose alone, and that serum concentration is strongly influenced by sex, age, smoking habit, drug-drug interactions and variations in the 1A2, 2D6 and 3A4 genotypes. Anticonvulsants are not recommended as a primary prophylaxis for clozapine-induced seizures. When deemed necessary as secondary prophylaxis, the clinician's choice should consider drug-drug interactions that may increase/decrease clozapine serum concentration and lead to more side effects, including neutropenia/agranulocytosis and seizures, or compromise therapeutic response. Recommendations for primary and secondary prophylaxis of clozapine related-seizures are provided.

Graphene oxide/MnO2 nanocomposite as destructive adsorbent of nerve-agent simulants in aqueous media

Czech Academy of Sciences Publication Activity Database

Šťastný, Martin; Tolasz, Jakub; Štengl, Václav; Henych, Jiří; Žižka, D.

2017-01-01

Roč. 412, AUG (2017), s. 19-28 ISSN 0169-4332 R&D Projects: GA MŠk(CZ) LM2015073 Institutional support: RVO:61388980 Keywords : Graphene oxide * Manganese oxide * Nanocomposite * Destructive adsorption * Nerve agent simulants * Dimethyl methyl phosphonate (DMMP) * Triethyl phosphate (TEP) Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 3.387, year: 2016

Stimulus-induced, sleep-bound, focal seizures: a case report.

Science.gov (United States)

Siclari, Francesca; Nobili, Lino; Lo Russo, Giorgio; Moscato, Alessio; Buck, Alfred; Bassetti, Claudio L; Khatami, Ramin

2011-12-01

In nocturnal frontal lobe epilepsy (NFLE), seizures occur almost exclusively during NREM sleep. Why precisely these seizures are sleep-bound remains unknown. Studies of patients with nonlesional familial forms of NFLE have suggested the arousal system may play a major role in their pathogenesis. We report the case of a patient with pharmaco-resistant, probably cryptogenic form of non-familial NFLE and strictly sleep-bound seizures that could be elicited by alerting stimuli and were associated with ictal bilateral thalamic and right orbital-insular hyperperfusion on SPECT imaging. Case report. University Hospital Zurich. One patient with pharmaco-resistant epilepsy. This case shows that the arousal system plays a fundamental role also in cryptogenic non-familial forms of NFLE.

Anticonvulsant effect of time-restricted feeding in a pilocarpine-induced seizure model: Metabolic and epigenetic implications.

Directory of Open Access Journals (Sweden)

Jorge eLandgrave-Gómez

2016-01-01

Full Text Available A new generation of antiepileptic drugs has emerged; however, one-third of epilepsy patients do not properly respond to pharmacological treatments. The purpose of the present study was to investigate whether time-restricted feeding has an anticonvulsant effect and whether this restrictive diet promotes changes in energy metabolism and epigenetic modifications in a pilocarpine-induced seizure model. To resolve our hypothesis, one group of rats had free access to food and water ad libitum (AL and a second group underwent a time-restricted feeding (TRF schedule. We used the lithium-pilocarpine model to induce status epilepticus (SE, and behavioral seizure monitoring was analyzed. Additionally, an electroencephalography (EEG recording was performed to verify the effect of TRF on cortical electrical activity after a pilocarpine injection. For biochemical analysis, animals were sacrificed 24 hours after SE and hippocampal homogenates were used to evaluate the proteins related to metabolism and chromatin structure. Our results showed that TRF had an anticonvulsant effect as measured by the prolonged latency of forelimb clonus seizure, a decrease in the seizure severity score and fewer animals reaching SE. Additionally, the power of the late phase EEG recordings in the AL group was significantly higher than the TRF group. Moreover, we found that TRF is capable of inducing alterations in signaling pathways that regulate energy metabolism, including an increase in the phosphorylation of AMP dependent kinase (AMPK and a decrease in the phosphorylation of Akt kinase. Furthermore, we found that TRF was able to significantly increase the beta hydroxybutyrate (β-HB concentration, an endogenous inhibitor of histone deacetylases (HDACs. Finally, we found a significant decrease in HDAC activity as well as an increase in acetylation on histone 3 (H3 in hippocampal homogenates from the TRF group. These findings suggest that alterations in energy metabolism and the

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

National Research Council Canada - National Science Library

Adams, T. K; Capacio, B. R; Smith, J. R; Whalley, C. E; Korte, W. D

2004-01-01

The fluoride reactivation process was evaluated for measuring the level of sarin or soman nerve agents reactivated from substrates in plasma and tissue from in vivo exposed guinea pigs (Cava porcellus...

Studies on the post-ictal rise in seizure threshold. [Rats

Energy Technology Data Exchange (ETDEWEB)

Nutt, D.J.; Cowen, P.J.; Green, A.R.

1981-05-08

Seizure thresholds were determined by timed infusion of a convulsant drug. Following an electroconvulsive shock (ECS) rats exhibited a raised seizure threshold to infusion of the GABA antagonist drugs, pentylenetetrazol, bicuculline and isopropyl-bicyclophosphate, but not to the glycine antagonist strychnine or the 5-HT agonist, quipazine. The increase in threshold was seen following a bicuculline-induced seizure and 30 min following the last of a course of ECS given once daily for 10 days. The rise in seizure threshold still occurred when animals were pretreated with alpha-methyl-p-tyrosine (200 mg . kg-1), p-chlorophenylalanine (200 mg . kg-2), naloxone (1 mg . kg-1) or indomethacin (20 mg . kg-1). Diazepam (2 mg . kg-1), flurazepam (10 mg . kg-1) and sodium valproate (400 mg . kg-1) elevated basal seizure threshold and a further rise followed the ECS. Phenytoin (40 mg . kg-1) and carbamazepine (40 mg . kg-1) had no effect on basal seizure threshold or the ECS-induce rise. (

Flexible carbon nanotube sensors for nerve agent simulants

Energy Technology Data Exchange (ETDEWEB)

Cattanach, Kyle; Kulkarni, Rashmi D; Kozlov, Mikhail; Manohar, Sanjeev K [Alan G MacDiarmid Center for Innovation, Department of Chemistry, University of Texas at Dallas, Richardson 75083-0688 (United States)

2006-08-28

Chemiresistor-based vapour sensors made from network films of single-walled carbon nanotube (SWNT) bundles on flexible plastic substrates (polyethylene terephthalate, PET) can be used to detect chemical warfare agent simulants for the nerve agents Sarin (diisopropyl methylphosphonate, DIMP) and Soman (dimethyl methylphosphonate, DMMP). Large, reproducible resistance changes (75-150%), are observed upon exposure to DIMP or DMMP vapours, and concentrations as low as 25 ppm can be detected. Robust sensor response to simulant vapours is observed even in the presence of large equilibrium concentrations of interferent vapours commonly found in battle-space environments, such as hexane, xylene and water (10 000 ppm each), suggesting that both DIMP and DMMP vapours are capable of selectively displacing other vapours from the walls of the SWNTs. Response to these interferent vapours can be effectively filtered out by using a 2 {mu}m thick barrier film of the chemoselective polymer polyisobutylene (PIB) on the SWNT surface. These network films are composed of a 1-2 {mu}m thick non-woven mesh of SWNT bundles (15-30 nm diameter), whose sensor response is qualitatively and quantitatively different from previous studies on individual SWNTs, or a network of individual SWNTs, suggesting that vapour sorption at interbundle sites could be playing an important role. This study also shows that the line patterning method used in device fabrication to obtain any desired pattern of films of SWNTs on flexible substrates can be used to rapidly screen simulants at high concentrations before developing more complicated sensor systems.

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor.

Science.gov (United States)

Amini-Khoei, Hossein; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Haj-Mirzaian, Arvin; Shirzadian, Armin; Hasanvand, Amin; Balali-Dehkordi, Shima; Hassanipoor, Mahsa; Dehpour, Ahmad Reza

2018-03-20

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg). We found that inducible NOS inhibitor, aminoguanidine (100 mg/kg), had no effect on the anti-seizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of sub-effective dose of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of nNOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

The effects of inferior olive lesion on strychnine seizure

International Nuclear Information System (INIS)

Anderson, M.C.; Chung, E.Y.; Van Woert, M.H.

1990-01-01

Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable [ 3 H]AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid] binding in cerebella from inferior olive-lesioned rats was observed, but no difference in [ 3 H]AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10 imine] were tested as anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the [ 3 H]AMPA binding data

Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats.

Science.gov (United States)

Tang, Nou-Ying; Lin, Yi-Wen; Ho, Tin-Yun; Cheng, Chin-Yi; Chen, Chao-Hsiang; Hsieh, Ching-Liang

2017-01-01

Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p.) and subsequently investigated the effect of Uncaria rhynchophylla (UR) and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg). Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons.

How the environment shapes genetically induced seizure activity in rats

NARCIS (Netherlands)

Schridde, U.; Luijtelaar, E.L.J.M. van; Takahashi, T.; Fukuyama, Y.

2008-01-01

Underling biology that governs the age-dependent seizure susceptibility is a new, exciting research field for every pediatric epileptologists and developmental nouroscientists. From daily practice, clinicians are well aware about a close correlation between the degree of seizure susceptibility and

M Current-Based Therapies for Nerve Agent Seizures

Science.gov (United States)

2013-07-01

synaptic transmission. Science 264, 107-111. Wolff, C., Gillard , M., Fuks, B., & Chatelain, P. (2005). [3H]linopirdine binding to rat brain membranes is...supporting hippocampal synaptic transmission. Science 264, 107–111. Wolff C, Gillard M, Fuks B & Chatelain P (2005). [3H]Linopirdine binding to rat

Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

NARCIS (Netherlands)

Hoeger, S.; Bergstraesser, C.; Selhorst, J.; Fontana, J.; Birck, R.; Waldherr, R.; Beck, G.; Sticht, C.; Seelen, M. A.; van Son, W. J.; Leuvenink, H.; Ploeg, R.; Schnuelle, P.; Yard, B. A.

Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability

Chiral separation of G-type chemical warfare nerve agents via analytical supercritical fluid chromatography.

Science.gov (United States)

Kasten, Shane A; Zulli, Steven; Jones, Jonathan L; Dephillipo, Thomas; Cerasoli, Douglas M

2014-12-01

Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G-type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical-scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(-) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(-) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc.

Cranial nerve threshold for thermal injury induced by MRI-guided high-intensity focused ultrasound (MRgHIFU): preliminary results on an optic nerve model.

Science.gov (United States)

Harnof, Sagi; Zibly, Zion; Cohen, Zvi; Shaw, Andrew; Schlaff, Cody; Kassel, Neal F

2013-04-01

Future clinical applications of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) are moving toward the management of different intracranial pathologies. We sought to validate the production, safety, and efficacy of thermal injury to cranial nerves generated by MRgHIFU. In this study, five female domestic pigs underwent a standard bifrontal craniectomy under general anesthesia. Treatment was then given using an MRgHIFU system to induce hyperthermic ablative sonication (6 to 10 s; 50 to 2000 J.) Histological analyses were done to confirm nerve damage; temperature measured on the optic nerve was approximately 53.4°C (range: 39°C to 70°C.) Histology demonstrated a clear definition between a necrotic, transitional zone, and normal tissue. MRgHIFU induces targeted thermal injury to nervous tissue within a specific threshold of 50°C to 60°C with the tissue near the sonication center yielding the greatest effect; adjacent tissue showed minimal changes. Additional studies utilizing this technology are required to further establish accurate threshold parameters for optic nerve thermo-ablation.

Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet

Science.gov (United States)

Selter, Jessica H.; Turner, Zahava; Doerrer, Sarah C.; Kossoff, Eric H.

2014-01-01

Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007-2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments lead to >50% further seizure reduction in-18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs. 15%, p = 0.08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit). PMID:24859788

The effects of anticonvulsants on 4-aminopyridine-induced bursting: in vitro studies on rat peripheral nerve and dorsal roots.

Science.gov (United States)

Lees, G.

1996-01-01

1. Aminopyridines have been used as beneficial symptomatic treatments in a variety of neurological conditions including multiple sclerosis but have been associated with considerable toxicity in the form of abdominal pain, paraesthesias and (rarely) convulsions. 2. Extracellular and intracellular recording was used to characterize action potentials in rat sciatic nerves and dorsal roots and the effects of 4-aminopyridine (4-AP). 3. In sciatic nerve trunks, 1 mM 4-AP produced pronounced after potentials at room temperature secondary to regenerative firing in affected axons (5-10 spikes per stimulus). At physiological temperatures, after potentials (2-3 spikes) were greatly attenuated in peripheral axons. 4. 4-AP evoked more pronounced and prolonged after discharges in isolated dorsal roots at 37 degrees C (3-5.5 mV and 80-100 ms succeeded by a smaller inhibitory/depolarizing voltage shift) which were used to assess the effects of anticonvulsants. 5. Phenytoin, carbamazepine and lamotrigine dose-dependently reduced the area of 4-AP-induced after potentials at 100 and 320 microM but the amplitude of compound action potentials (evoked at 0.5 Hz) was depressed in parallel. 6. The tonic block of sensory action potentials by all three drugs (at 320 microM) was enhanced by high frequency stimulation (5-500 Hz). 7. The lack of selectivity of these frequency-dependent Na+ channel blockers for burst firing compared to low-frequency spikes, is discussed in contrast to their effects on 4-AP-induced seizures and paroxysmal activity in CNS tissue (which is associated with large and sustained depolarizing plateau potentials). 8. In conclusion, these in vitro results confirm the marked sensitivity of sensory axons to 4-AP (the presumptive basis for paraesthesias). Burst firing was not preferentially impaired at relatively high concentrations suggesting that anticonvulsants will not overcome the toxic peripheral actions of 4-AP in neurological patients. PMID:8821551

Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

Directory of Open Access Journals (Sweden)

Zhen Feng

2015-01-01

Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

The role of the oximes HI-6 and HS-6 inside human acetylcholinesterase inhibited with nerve agents: a computational study.

Science.gov (United States)

Cuya, Teobaldo; Gonçalves, Arlan da Silva; da Silva, Jorge Alberto Valle; Ramalho, Teodorico C; Kuca, Kamil; C C França, Tanos

2017-10-27

The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS-6) are isomers differing from each other only by the position of the carbamoyl group on the pyridine ring. However, this slight difference was verified to be responsible for big differences in the percentual of reactivation of acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin, cyclosarin, and VX. In order to try to find out the reason for this, a computational study involving molecular docking, molecular dynamics, and binding energies calculations, was performed on the binding modes of HI-6 and HS-6 on human AChE (HssAChE) inhibited by those nerve agents.

Absence seizure

Science.gov (United States)

Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Elsevier; 2016:chap 101. Marcdante KJ, Kliegman RM. Seizures (paroxysmal disorders). In: Marcdante KJ, Kliegman RM, eds. Nelson Essentials ...

Apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy

Directory of Open Access Journals (Sweden)

Lei ZHAO

2011-09-01

Full Text Available Objective To explore the apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy.Methods Thirty healthy adult SD rats were randomly divided into three groups,namely,ventral root transection group(VRT group,received left L4-L6 ventral rhizotomy,dorsal root transection group(DRT group,received left L4-L6 dorsal rhizotomy,and sciatic nerve transection group(SNT group,received left sciatic nerve transection.Each group comprised 10 SD rats.The bilateral gastrocnemius was harvested 10 weeks after operation to observe the apoptosis and Fas/FasL expression of the skeletal muscle cells through fluorescent labeling,transmission electron microscopy,and immunohistochemistry.Result Ten weeks after the denervation,apoptosis-related changes,especially obvious changes of the nuclear apoptotic morphology,were observed in the skeletal muscle cells.The aggregation degree of the nucleus and the expression of Fas/FasL increased in the following order: DRT group,VRT group,and SNT group.No apoptotic body,but early apoptotic morphology,was found in the denervated gastrocnemius through transmission electron microscopy.Conclusions The effect of motor nerve injury on skeletal muscle atrophy is more serious than that of sensory nerve injury.The rebuilding of motor nerves should be preferentially considered in the clinical treatment of muscle atrophy induced by denervation.

Emotion-induced myoclonic absence-like seizures in a patient with inv-dup(15) syndrome: a clinical, EEG, and molecular genetic study.

Science.gov (United States)

Aguglia, U; Le Piane, E; Gambardella, A; Messina, D; Russo, C; Sirchia, S M; Porta, G; Quattrone, A

1999-09-01

We have described a clinical EEG and molecular genetic study of a 9-year-old boy with inv-dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5-20 s after the onset of repeated cheek-kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence-like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11-q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral gamma-aminobutyric acid (GABA)-mediated inhibition accounts for the severe epilepsy that we observed in this patient.

Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

Science.gov (United States)

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Bouchard, Caroline; Ardell, Jeffrey L; Foreman, Robert D; Armour, J Andrew

2006-11-01

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

Directory of Open Access Journals (Sweden)

VENKATA R.K. THIAGARAJAN

2014-09-01

Full Text Available The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

Science.gov (United States)

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nerve crush but not displacement-induced stretch of the intra-arachnoidal facial nerve promotes facial palsy after cerebellopontine angle surgery.

Science.gov (United States)

Bendella, Habib; Brackmann, Derald E; Goldbrunner, Roland; Angelov, Doychin N

2016-10-01

Little is known about the reasons for occurrence of facial nerve palsy after removal of cerebellopontine angle tumors. Since the intra-arachnoidal portion of the facial nerve is considered to be so vulnerable that even the slightest tension or pinch may result in ruptured axons, we tested whether a graded stretch or controlled crush would affect the postoperative motor performance of the facial (vibrissal) muscle in rats. Thirty Wistar rats, divided into five groups (one with intact controls and four with facial nerve lesions), were used. Under inhalation anesthesia, the occipital squama was opened, the cerebellum gently retracted to the left, and the intra-arachnoidal segment of the right facial nerve exposed. A mechanical displacement of the brainstem with 1 or 3 mm toward the midline or an electromagnet-controlled crush of the facial nerve with a tweezers at a closure velocity of 50 and 100 mm/s was applied. On the next day, whisking motor performance was determined by video-based motion analysis. Even the larger (with 3 mm) mechanical displacement of the brainstem had no harmful effect: The amplitude of the vibrissal whisks was in the normal range of 50°-60°. On the other hand, even the light nerve crush (50 mm/s) injured the facial nerve and resulted in paralyzed vibrissal muscles (amplitude of 10°-15°). We conclude that, contrary to the generally acknowledged assumptions, it is the nerve crush but not the displacement-induced stretching of the intra-arachnoidal facial trunk that promotes facial palsy after cerebellopontine angle surgery in rats.

Clinical Microbiological Aspects of Epileptic Seizures in the Tropical Countries with Specific Focus on Nigeria

Directory of Open Access Journals (Sweden)

Ijeoma Kanu

2005-01-01

Full Text Available Epilepsy is a common neurological disorder; however, in Nigeria and other tropical regions, the causes of epileptic seizures differ greatly in etiology. This paper is an attempt to highlight some possible microbiological aspects of epileptic seizures. A literature review was carried out to identify the extent to which microbial infections were involved in the elicitation of epileptic seizures. Data were collected from several clinics in the community and hospitals in Nigeria and correlated with the evidence from the literature review. It was found that different microbial agents including viral, bacterial, protozoa, and fungal agents were involved in several aspects of epileptic seizures. Malaria was found to cause more than 88% of childhood epileptic seizures and 12% of adult seizures. Generalized tonic-clonic seizures occurred in more than 40% of adult patients. Partial seizures were uncommon. Cases of epileptic seizures associated with bacteria (e.g., brucellosis, viral, fungal, and protozoa infections were frequently reported. Malaria, tapeworm, and cysticercosis were some of the common infectious causes of epilepsy; however, in some cases, the cause remained unknown. From these findings, it was evident that microbiological aspects of epilepsies are possible research areas that might be developed. It is believed that the unraveling of the various microbiological factors in epileptic seizures would have important implications for understanding the underlying neurobiology, evaluating treatment strategies, and perhaps planning health-care resources for the affected. It will also help to improve the prognostic factors in initial seizure symptomatic etiology and presence of any structural cerebral abnormalities.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

Energy Technology Data Exchange (ETDEWEB)

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.; Munro, N.B.; Linnabary, R.D. (Environmental Sciences Division, Oak Ridge National Laboratory, TN (United States))

1992-09-01

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

A KCNQ channel opener for experimental neonatal seizures and status epilepticus

Science.gov (United States)

Raol, YogendraSinh H.; Lapides, David A.; Keating, Jeffery; Brooks-Kayal, Amy R.; Cooper, Edward C.

2009-01-01

Objective Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage-gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures. Methods We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures. Results Unlike phenobarbital or diazepam, flupirtine prevented animals from developing status epilepticus (SE) when administered prior to kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate-induced SE. Flupirtine caused dose-related sedation and suppressed EEG activity, but did not result in respiratory suppression or result in any mortality. Interpretation Flupirtine appears more effective than either of two commonly used anti-epileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children. PMID:19334075

Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet.

Science.gov (United States)

Selter, Jessica H; Turner, Zahava; Doerrer, Sarah C; Kossoff, Eric H

2015-01-01

Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit). © The Author(s) 2014.

Long-Term Intake of Uncaria rhynchophylla Reduces S100B and RAGE Protein Levels in Kainic Acid-Induced Epileptic Seizures Rats

Directory of Open Access Journals (Sweden)

Nou-Ying Tang

2017-01-01

Full Text Available Epileptic seizures are crucial clinical manifestations of recurrent neuronal discharges in the brain. An imbalance between the excitatory and inhibitory neuronal discharges causes brain damage and cell loss. Herbal medicines offer alternative treatment options for epilepsy because of their low cost and few side effects. We established a rat epilepsy model by injecting kainic acid (KA, 12 mg/kg, i.p. and subsequently investigated the effect of Uncaria rhynchophylla (UR and its underlying mechanisms. Electroencephalogram and epileptic behaviors revealed that the KA injection induced epileptic seizures. Following KA injection, S100B levels increased in the hippocampus. This phenomenon was attenuated by the oral administration of UR and valproic acid (VA, 250 mg/kg. Both drugs significantly reversed receptor potentiation for advanced glycation end product proteins. Rats with KA-induced epilepsy exhibited no increase in the expression of metabotropic glutamate receptor 3, monocyte chemoattractant protein 1, and chemokine receptor type 2, which play a role in inflammation. Our results provide novel and detailed mechanisms, explaining the role of UR in KA-induced epileptic seizures in hippocampal CA1 neurons.

Seizure-Induced Oxidative Stress in Temporal Lobe Epilepsy

Directory of Open Access Journals (Sweden)

Sreekanth Puttachary

2015-01-01

Full Text Available An insult to the brain (such as the first seizure causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS. ROS and RNS produced during status epilepticus (SE overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS, which ultimately establish into temporal lobe epilepsy (TLE. This review discusses some of these issues. Though antiepileptic drugs (AEDs are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy.

Ghrelin ameliorates nerve growth factor Dysmetabolism and inflammation in STZ-induced diabetic rats.

Science.gov (United States)

Zhao, Yuxing; Shen, Zhaoxing; Zhang, Dongling; Luo, Huiqiong; Chen, Jinliang; Sun, Yue; Xiao, Qian

2017-06-01

Diabetic encephalopathy is characterized by cognitive impairment and neuroinflammation, deficient neurotrophic support, and neuronal and synaptic loss. Ghrelin, a 28 amino acid peptide, is associated with neuromodulation and cognitive improvement, which has been considered as a potential protective agent for several neurodegenerative diseases. Here we sought to investigate the role of ghrelin in preventing diabetic-related neuropathology. We found that ghrelin attenuated astrocytic activation and reduced levels of interleukin-6 and tumor necrosis factor-α in streptozotocin-induced diabetic rats. In addition, ghrelin inhibited p38 mitogen-associated protein kinase activation. The upregulation of nerve growth factor (NGF) precursor and matrix metalloproteinase (MMP)-9 and downregulation of mature NGF and MMP-7 in the diabetic brain were reversed by ghrelin. Treatment with ghrelin elevated synaptophysin expression and synaptic density in diabetic rats. Taken together, our results demonstrate that ghrelin ameliorates diabetes-related neurodegeneration by preventing NGF dysmetabolism and synaptic degeneration through regulating MMP levels as well as inhibiting neuroinflammation.

Use of antioxidants for the prophylaxis of cold-induced peripheral nerve injury.

Science.gov (United States)

Teixeira, Fernanda; Pollock, Martin; Karim, Alveera; Jiang, Yuying

2002-09-01

"Trench foot" is a particular risk for those involved in adventure tourism, for soldiers in winter mountain training exercises, and for the homeless. Nonfreezing cold nerve injury is characterized by axonal degeneration, which is attributed to free radicals released during cycles of ischemia and reperfusion. This pilot study sought to determine whether the administration of antioxidants might prevent or ameliorate the development of cold nerve injury. Twenty-six rats were divided into two groups. Group 1 animals received, by gavage, a mixture of vitamin C (150 mg/kg/d), vitamin E (100 mg/kg/d), and N-acetyl-L-cysteine (250 mg/kg/d) daily for 4 weeks. Allopurinol (20 mg/kg/d) was added in the last 4 days of treatment. Group 2 animals served as controls and did not receive any antioxidant supplements. After 1 month, two cycles of sciatic nerve cooling (0 degrees C) were induced in 10 controls and 10 experimental animals using circulating water through a nerve cuff. Six additional control animals were subjected to surgery but did not undergo nerve cooling. All animals were killed on the third postoperative day, and their nerves were processed for ultrastructural and quantitative studies. The proportion of degenerated myelinated and unmyelinated axons showed no significant difference between treated and untreated animals. We conclude that the administration of commonly used antioxidants does not prevent cold nerve injury.

Laser-based instrumentation for the detection of chemical agents

International Nuclear Information System (INIS)

Hartford, A. Jr.; Sander, R.K.; Quigley, G.P.; Radziemski, L.J.; Cremers, D.A.

1982-01-01

Several laser-based techniques are being evaluated for the remote, point, and surface detection of chemical agents. Among the methods under investigation are optoacoustic spectroscopy, laser-induced breakdown spectroscopy (LIBS), and synchronous detection of laser-induced fluorescence (SDLIF). Optoacoustic detection has already been shown to be capable of extremely sensitive point detection. Its application to remote sensing of chemical agents is currently being evaluated. Atomic emission from the region of a laser-generated plasma has been used to identify the characteristic elements contained in nerve (P and F) and blister (S and Cl) agents. Employing this LIBS approach, detection of chemical agent simulants dispersed in air and adsorbed on a variety of surfaces has been achieved. Synchronous detection of laser-induced fluorescence provides an attractive alternative to conventional LIF, in that an artificial narrowing of the fluorescence emission is obtained. The application of this technique to chemical agent simulants has been successfully demonstrated. 19 figures

Hungry Neurons: Metabolic Insights on Seizure Dynamics

Directory of Open Access Journals (Sweden)

Paolo Bazzigaluppi

2017-10-01

Full Text Available Epilepsy afflicts up to 1.6% of the population and the mechanisms underlying the appearance of seizures are still not understood. In past years, many efforts have been spent trying to understand the mechanisms underlying the excessive and synchronous firing of neurons. Traditionally, attention was pointed towards synaptic (dysfunction and extracellular ionic species (dysregulation. Recently, novel clinical and preclinical studies explored the role of brain metabolism (i.e., glucose utilization of seizures pathophysiology revealing (in most cases reduced metabolism in the inter-ictal period and increased metabolism in the seconds preceding and during the appearance of seizures. In the present review, we summarize the clinical and preclinical observations showing metabolic dysregulation during epileptogenesis, seizure initiation, and termination, and in the inter-ictal period. Recent preclinical studies have shown that 2-Deoxyglucose (2-DG, a glycolysis blocker is a novel therapeutic approach to reduce seizures. Furthermore, we present initial evidence for the effectiveness of 2-DG in arresting 4-Aminopyridine induced neocortical seizures in vivo in the mouse.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

Directory of Open Access Journals (Sweden)

Yoshiki Shionoya

Full Text Available This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB in a canine model. This study involved two experiments-in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

Science.gov (United States)

Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

2017-01-01

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

Modulation of seizure activity in mice by metabotropic glutamate receptor ligands

DEFF Research Database (Denmark)

Dalby, Nils Ole; Thomsen, C

1996-01-01

The anticonvulsant properties of ligands at metabotropic glutamate receptors (mGluRs) were examined in different seizure models by use of intracerebroventricular infusion. The mGluR1a antagonist/mGluR2 agonist, (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG] dose-dependently antagonized...... pentylenetetrazol- and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-2-carboxylate (DMCM)-induced clonic convulsions in mice with ED50 values of 400 and 180 nmol/mice, respectively. A modest increase in electrical seizure threshold was observed in mice injected with (S)-4C3HPG. No effect on seizures induced...... by systemic administration of N-methyl-D-aspartate was observed by prior intracerebroventricular infusion of (S)-4C3HPG. The more selective (but less potent) mGluR1a antagonist, (S)-4-carboxyphenylglycine, was a weak anticonvulsant in similar seizure models with the exception of convulsions induced...

Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

Energy Technology Data Exchange (ETDEWEB)

Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W. [Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow (Poland)

1997-04-14

The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [{sup 3}H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [{sup 3}H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [{sup 3}H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [{sup 3}H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [{sup 3}H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

International Nuclear Information System (INIS)

Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W.

1997-01-01

The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [ 3 H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [ 3 H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [ 3 H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [ 3 H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [ 3 H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

Directory of Open Access Journals (Sweden)

Ma Fei

2012-12-01

Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

Seizure outcomes in non-resective epilepsy surgery: An update

Science.gov (United States)

Englot, Dario J.; Birk, Harjus; Chang, Edward F.

2016-01-01

In approximately 30% of patients with epilepsy, seizures are refractory to medical therapy, leading to significant morbidity and increased mortality. Substantial evidence has demonstrated the benefit of surgical resection in patients with drug-resistant focal epilepsy, and in the present journal, we recently reviewed seizure outcomes in resective epilepsy surgery. However, not all patients are candidates for or amenable to open surgical resection for epilepsy. Fortunately, several non-resective surgical options are now available at various epilepsy centers, including novel therapies which have been pioneered in recent years. Ablative procedures such as stereotactic laser ablation and stereotactic radiosurgery offer minimally invasive alternatives to open surgery with relatively favorable seizure outcomes, particularly in patients with mesial temporal lobe epilepsy. For certain individuals who are not candidates for ablation or resection, palliative neuromodulation procedures such as vagus nerve stimulation, deep brain stimulation, or responsive neurostimulation may result in a significant decrease in seizure frequency and improved quality of life. Finally, disconnection procedures such as multiple subpial transections and corpus callosotomy continue to play a role in select patients with an eloquent epileptogenic zone or intractable atonic seizures, respectively. Overall, open surgical resection remains the gold standard treatment for drug-resistant epilepsy, although it is significantly under-utilized. While non-resective epilepsy procedures have not replaced the need for resection, there is hope that these additional surgical options will increase the number of patients who receive treatment for this devastating disorder - particularly individuals who are not candidates for or who have failed resection. PMID:27206422

Cerebrospinal fluid findings after epileptic seizures.

Science.gov (United States)

Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

2015-12-01

We aimed to evaluate ictally-induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work-up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF-to-serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non-inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF-to-serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further-reaching pathological implications besides their postictal character.

Seizure ending signs in patients with dyscognitive focal seizures.

Science.gov (United States)

Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

2015-09-01

Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

M. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.

Science.gov (United States)

Bahia El Idrissi, Nawal; Das, Pranab K; Fluiter, Kees; Rosa, Patricia S; Vreijling, Jeroen; Troost, Dirk; Morgan, B Paul; Baas, Frank; Ramaglia, Valeria

2015-05-01

Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. We previously identified the membrane attack complex (MAC) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. Here, we determined the contribution of the MAC to nerve damage caused by Mycobacterium leprae and its components in mouse. Furthermore, we studied the association between MAC and the key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy patients. Intraneural injections of M. leprae sonicate induced MAC deposition and pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin and axons. Complement activation occurred mainly via the lectin pathway and the principal activator was LAM. In leprosy nerves, the extent of LAM and MAC immunoreactivity was robust and significantly higher in multibacillary compared to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly significant association between LAM and MAC in the diseased samples (r = 0.9601, p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for this M. leprae antigen in complement activation and nerve damage in leprosy. Our findings demonstrate that MAC contributes to nerve damage in a model of M. leprae-induced nerve injury and its inhibition is neuroprotective. In addition, our data identified LAM as the key pathogen associated molecule that activates complement and causes nerve damage. Taken together our data imply an important role of complement in nerve damage in leprosy and may inform the development of novel therapeutics for patients.

Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

Science.gov (United States)

Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

2013-01-01

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model.

Science.gov (United States)

Cho, Hyong-Ho; Jang, Sujeong; Lee, Sang-Chul; Jeong, Han-Seong; Park, Jong-Seong; Han, Jae-Young; Lee, Kyung-Hwa; Cho, Yong-Bum

2010-05-01

The purpose of this study was to investigate the effects of platelet-rich plasma (PRP) and neural-induced human mesenchymal stem cells (nMSCs) on axonal regeneration from a facial nerve axotomy injury in a guinea pig model. Prospective, controlled animal study. Experiments involved the transection and repair of the facial nerve in 24 albino guinea pigs. Four groups were created based on the method of repair: suture only (group I, control group); PRP with suture (group II); nMSCs with suture (group III); and PRP and nMSCs with suture (group IV). Each method of repair was applied immediately after nerve transection. The outcomes measured were: 1) functional outcome measurement (vibrissae and eyelid closure movements); 2) electrophysiologic evaluation; 3) neurotrophic factors assay; and 4) histologic evaluation. With respect to the functional outcome measurement, the functional outcomes improved after transection and reanastomosis in all groups. The control group was the slowest to demonstrate recovery of movement after transection and reanastomosis. The other three groups (groups II, III, and IV) had significant improvement in function compared to the control group 4 weeks after surgery (P facial nerve regeneration in an animal model of facial nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010.

Seizures and Teens: Stress, Sleep, & Seizures

Science.gov (United States)

Shafer, Patricia Osborne

2007-01-01

Most parents are used to erratic sleep patterns and mood swings in their teenagers. When these occur in an adolescent with seizures, however, the parent may wonder if sleep and mood problems are related to seizures. Sorting out the cause and effects of sleep in an adolescent with seizures can be confusing. Since stress can be a contributor to both…

Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents

OpenAIRE

Geyer, Brian C.; Kannan, Latha; Garnaud, Pierre-Emmanuel; Broomfield, Clarence A.; Cadieux, C. Linn; Cherni, Irene; Hodgins, Sean M.; Kasten, Shane A.; Kelley, Karli; Kilbourne, Jacquelyn; Oliver, Zeke P.; Otto, Tamara C.; Puffenberger, Ian; Reeves, Tony E.; Robbins, Neil

2010-01-01

The concept of using cholinesterase bioscavengers for prophylaxis against organophosphorous nerve agents and pesticides has progressed from the bench to clinical trial. However, the supply of the native human proteins is either limited (e.g., plasma-derived butyrylcholinesterase and erythrocytic acetylcholinesterase) or nonexisting (synaptic acetylcholinesterase). Here we identify a unique form of recombinant human butyrylcholinesterase that mimics the native enzyme assembly into tetramers; t...

Termination of seizure clusters is related to the duration of focal seizures.

Science.gov (United States)

Ferastraoaru, Victor; Schulze-Bonhage, Andreas; Lipton, Richard B; Dümpelmann, Matthias; Legatt, Alan D; Blumberg, Julie; Haut, Sheryl R

2016-06-01

Clustered seizures are characterized by shorter than usual interseizure intervals and pose increased morbidity risk. This study examines the characteristics of seizures that cluster, with special attention to the final seizure in a cluster. This is a retrospective analysis of long-term inpatient monitoring data from the EPILEPSIAE project. Patients underwent presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the occurrence of at least two consecutive seizures with interseizure intervals of <4 h. Other definitions of seizure clustering were examined in a sensitivity analysis. Seizures were classified into three contextually defined groups: isolated seizures (not meeting clustering criteria), terminal seizure (last seizure in a cluster), and intracluster seizures (any other seizures within a cluster). Seizure characteristics were compared among the three groups in terms of duration, type (focal seizures remaining restricted to one hemisphere vs. evolving bilaterally), seizure origin, and localization concordance among pairs of consecutive seizures. Among 92 subjects, 77 (83%) had at least one seizure cluster. The intracluster seizures were significantly shorter than the last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster resembled the isolated seizures in terms of duration. Although focal only (unilateral), seizures were shorter than seizures that evolved bilaterally and there was no correlation between the seizure type and the seizure position in relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more likely to cluster compared with other localizations (p = 0.009). Seizure pairs that are part of a cluster were more likely to have a concordant origin than were isolated seizures. Results were similar for the 2 h definition of clustering, but not for the 8 h definition of clustering. We demonstrated that intracluster seizures are short relative to isolated seizures and terminal seizures. Frontal

Anticonvulsant effect of ethanolic extract of Cyperus articulatus L. leaves on pentylenetetrazol induced seizure in mice

Directory of Open Access Journals (Sweden)

Oscar Herrera-Calderon

2018-01-01

Full Text Available Cyperus articulatus (CA rhizomes have demonstrated different properties on nervous system. However, the leaves still have not studied to treat epilepsy. The aim of this study was to determine the effect of CA ethanolic extract on pentylenetetrazol (PTZ induced seizures in mice as well as measuring its antioxidant activity in vivo and in vitro. Mice were divided into five groups: (1 control (PTZ 80 mg/kg; i.p., (2 PTZ-Diazepam (1 mg/kg; i.p., (3–5 PTZ-CA 50, PTZ-CA 150 and PTZ-CA 300 (50, 150 and 300 mg/kg of CA extract, 30 min prior to each PTZ injection. The PTZ-CA 150 group showed lower seizure scores (P < 0.01, latency (P < 0.01, frequency (P < 0.01 and duration (P < 0.01 than control group. The antioxidant activity of CA extract scavenged DPPH radical showed IC 50 = 16.9 ± 0.1 μg/mL and TEAC = 2.28 ± 0.08, mmol trolox/g of extract, the content of gamma amino butyric acid (GABA and malondialdehyde (MDA were significantly high (P < 0.01 at dose of 150 mg/kg (82 ± 1.2 ng/g tissue; 1.0 ± 2.2 mol/g tissue, respectively. The present research demonstrated that CA extract possesses a potential effect to prevent PTZ induced seizures, antioxidant activity in addition to increase GABA levels.

Endurance training induces structural and morphoquantitative changes in rat vagus nerve

Directory of Open Access Journals (Sweden)

Eduardo Pianca

2015-10-01

Full Text Available ABSTRACTIntroduction:Many nervous system tissues and cells suffers positive changes when faced to exercise training. However, data on vagus nerve adaptation from exercise-induced study is absent.Objective:To analyze the effect of an endurance training on the vagus nerve morphology of rats.Methods:Wistar rats (6 months of age were divided into two groups: control group (CG, n=8, and aerobic trained group (AT, n=8. AT was submitted to a treadmill training program of five times per week during 12 weeks. The maximum speed stipulated in the training protocol corresponded to 60% of the mean maximum intensity achieved by the group in the test of maximum effort.Results:Twelve weeks of treadmill training resulted in left ventricular hypertrophy in the AT group com-pared to CG. There was a significant increase in the area of both the myelinated and unmyelinated axons, and in the area of myelin sheath with training. The number of neurotubules and neurofilaments in myelinated fibers of aerobic trained group was significantly greater than CG (p≤0.05.Conclusion:Endurance training promoted significant increase in morphometric parameters of the vagus nerve in the same way it affect somatic nerves.

Non traumatic fractures of the lumbar spine and seizures: case report

Directory of Open Access Journals (Sweden)

Moscote-Salazar Luis Rafael

2015-12-01

Full Text Available Injury-induced seizures may appear clinically asymptomatic and can be easily monitored by the absence of trauma and post-ictal impairment of consciousness. Patients with epilepsy have a higher risk of compression fractures, leading to serious musculoskeletal injuries, this type of non-traumatic compression fractures of the spine secondary to seizures are rare lesions, and is produced by the severe contraction of the paraspinal muscles that can achieve the thoracic spine fracture. Seizures induced lesions may appear clinically asymptomatic and can be easily monitored by the absence of trauma and post-ictal impairment of consciousness. We present a case report.

Identifying seizure clusters in patients with psychogenic nonepileptic seizures.

Science.gov (United States)

Baird, Grayson L; Harlow, Lisa L; Machan, Jason T; Thomas, Dave; LaFrance, W C

2017-08-01

The present study explored how seizure clusters may be defined for those with psychogenic nonepileptic seizures (PNES), a topic for which there is a paucity of literature. The sample was drawn from a multisite randomized clinical trial for PNES; seizure data are from participants' seizure diaries. Three possible cluster definitions were examined: 1) common clinical definition, where ≥3 seizures in a day is considered a cluster, along with two novel statistical definitions, where ≥3 seizures in a day are considered a cluster if the observed number of seizures statistically exceeds what would be expected relative to a patient's: 1) average seizure rate prior to the trial, 2) observed seizure rate for the previous seven days. Prevalence of clusters was 62-68% depending on cluster definition used, and occurrence rate of clusters was 6-19% depending on cluster definition. Based on these data, clusters seem to be common in patients with PNES, and more research is needed to identify if clusters are related to triggers and outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

Directory of Open Access Journals (Sweden)

Daniele Bertoglio

2017-11-01

Full Text Available The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE. As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE. Wistar Han (Charles River, France and Sprague-Dawley (Harlan, The Netherlands rats were subjected to KASE using the Hellier kainic acid (KA and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG in a subgroup of animals, while animals were sacrificed 1 week (subacute phase and 12 weeks (chronic phase post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei, microglial activation (OX-42 and translocator protein, and neurodegeneration (Fluorojade C were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001 in SD/H (median 8.3 days animals compared to WH/CR (median 15.4 days. During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01. However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

Science.gov (United States)

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden

Tumors of the optic nerve

DEFF Research Database (Denmark)

Lindegaard, Jens; Heegaard, Steffen

2009-01-01

A variety of lesions may involve the optic nerve. Mainly, these lesions are inflammatory or vascular lesions that rarely necessitate surgery but may induce significant visual morbidity. Orbital tumors may induce proptosis, visual loss, relative afferent pupillary defect, disc edema and optic...... atrophy, but less than one-tenth of these tumors are confined to the optic nerve or its sheaths. No signs or symptoms are pathognomonic for tumors of the optic nerve. The tumors of the optic nerve may originate from the optic nerve itself (primary tumors) as a proliferation of cells normally present...... in the nerve (e.g., astrocytes and meningothelial cells). The optic nerve may also be invaded from tumors originating elsewhere (secondary tumors), invading the nerve from adjacent structures (e.g., choroidal melanoma and retinoblastoma) or from distant sites (e.g., lymphocytic infiltration and distant...

Ultraviolet Raman scattering from persistent chemical warfare agents

Science.gov (United States)

Kullander, Fredrik; Wästerby, Pär.; Landström, Lars

2016-05-01

Laser induced Raman scattering at excitation wavelengths in the middle ultraviolet was examined using a pulsed tunable laser based spectrometer system. Droplets of chemical warfare agents, with a volume of 2 μl, were placed on a silicon surface and irradiated with sequences of laser pulses. The Raman scattering from V-series nerve agents, Tabun (GA) and Mustard gas (HD) was studied with the aim of finding the optimum parameters and the requirements for a detection system. A particular emphasis was put on V-agents that have been previously shown to yield relatively weak Raman scattering in this excitation band.

Febrile Seizure Simulation

Directory of Open Access Journals (Sweden)

Victor Cisneros

2017-01-01

Full Text Available Audience: This simulation session is appropriate for medical students, community physicians, or residents in emergency medicine, neurology, pediatrics, or family medicine. Introduction: Febrile seizures are the most common form of seizures in childhood; they are thought to occur in 2-5% of all children.1-3 Febrile seizures are defined as a seizure in association with a febrile illness in children without a central nervous system infection, previous afebrile seizure, known brain disorder, or electrolyte abnormalities. 1,2 They typically occur between 6 months and 18 months of age though they can occur up to 5 years of age.3 Febrile seizures are categorized as: simple (generalized seizure lasting less than 15 minutes in a child aged 6 months to 5 years, and less than 1 in a 24 hour period or complex (a focal seizure or generalized seizure lasting greater than 15 minutes, or multiple seizures in a 24 hour period. 1,3 Treatment for febrile seizures is based on treating the underlying cause of the fever and giving reassurance and education to the parents.2 Mortality is extremely rare, and there is no difference in the patient’s cognitive abilities after a febrile seizure, even when the seizure is prolonged.1 Objectives: At the end of this simulation session, the learner will be able to: 1 discuss the management of febrile seizures 2 discuss when placement of an advanced airway is indicated in the management of a febrile seizure 3 list the risk factors for febrile seizures 4 prepare a differential diagnosis for the causes of febrile seizures 5 educate family members on febrile seizures. Methods: This educational session is a high-fidelity simulation.

Management Of Post Stroke Seizures

Directory of Open Access Journals (Sweden)

Kavian Ghandehari

2017-02-01

treatment for patients with post-stroke seizures is still a controversial issue. Prospective studies in the literature showed that immediate treatment after a first unprovoked seizure does not improve the long-term remission rate. However, because of the physical and psychological influences of recurrent seizures, prophylactic treatment should be considered after a first unprovoked event in an elderly person at high risk of recurrence, taking into consideration the individuality of the patient and a discussion with the patient and his/her family about the risks and benefits of both options latest studies regarding post-stroke seizure treatment showed that 'new-generation' drugs, such as lamotrigine, gabapentin and levetiracetam, in low doses would be reasonable. Although several studies suggest that seizures alter the functional recovery after a stroke, it remains difficult to determine whether or not the occurrence of a second seizure in an untreated stroke patient might hamper the overall outcome. However, repeated seizures and status epilepticus worsen the neurological and mental condition of stroke patienton The decision to initiate antiepileptic drug treatment after a first or a second post-stroke seizure should therefore be individualized, primarily based on the functional impact of the first seizure episode and the patient's preference. Several converging findings suggest that the majority of first-generation antiepileptic drugs, particularly phenytoin, are not the most appropriate choice in stroke patients because of their potential harmful impact on functional recovery and bone health, their suboptimal pharmacokinetic profile and interaction with anticoagulants or salicylates, their greater likelihood to be poorly tolerated, and the lack of level A evidence regarding their specific use in elderly patients. Among the new-generation drugs that do not interact with anticoagulants, antiplatelet agents, or bone health, lamotrigine and gabapentine are the only two drugs

Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

Science.gov (United States)

Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

2018-01-01

A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury

International Nuclear Information System (INIS)

Li, Yonggang; Lein, Pamela J.; Liu, Cuimei; Bruun, Donald A.; Giulivi, Cecilia; Ford, Gregory D.; Tewolde, Teclemichael; Ross-Inta, Catherine; Ford, Byron D.

2012-01-01

Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague–Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. -- Highlights: ► NRG-1 blocked DFP induced neuronal injury. ► NRG-1 did not protect against seizures in rats exposed to DFP. ► NRG-1 blocked apoptosis and oxidative stress in the brains of DFP-intoxicated rats. ► Administration of NRG-1 at 1 h after DFP injection prevented delayed neuronal injury.

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

Science.gov (United States)

Nora, Tommi; Heinonen, Hanna; Tenhunen, Mirja; Rainesalo, Sirpa; Järvenpää, Soila; Lehtimäki, Kai; Peltola, Jukka

2018-01-01

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs.

Science.gov (United States)

Löscher, Wolfgang

2017-07-01

The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. Except for some early treatments, including bromides and phenobarbital, the antiseizure activity of all clinically used drugs was, for the most part, defined by acute seizure models in rodents using the maximal electroshock and subcutaneous pentylenetetrazole seizure tests and the electrically kindled rat. Unfortunately, the clinical evidence to date would suggest that none of these models, albeit useful, are likely to identify those therapeutics that will effectively manage patients with drug resistant seizures. Over the last 30 years, a number of animal models have been developed that display varying degrees of pharmacoresistance, such as the phenytoin- or lamotrigine-resistant kindled rat, the 6-Hz mouse model of partial seizures, the intrahippocampal kainate model in mice, or rats in which spontaneous recurrent seizures develops after inducing status epilepticus by chemical or electrical stimulation. As such, these models can be used to study mechanisms of drug resistance and may provide a unique opportunity for identifying a truly novel antiseizure drug (ASD), but thus far clinical evidence for this hope is lacking. Although animal models of drug resistant seizures are now included in ASD discovery approaches such as the ETSP (epilepsy therapy screening program), it is important to note that no single model has been validated for use to identify potential compounds for as yet drug resistant seizures, but rather a battery of such models should be employed, thus enhancing the sensitivity to discover novel, highly effective ASDs. The present review describes the previous and current approaches used in the search for new ASDs and offers some insight into future directions incorporating new and emerging animal models of therapy resistance.

Correlation between the distribution of 3H-labelled enkephalin in rat brain and the anatomical regions involved in enkephalin-induced seizures.

Science.gov (United States)

Haffmans, J; Blankwater, Y J; Ukponmwan, O E; Zijlstra, F J; Vincent, J E; Hespe, W; Dzoljic, M R

1983-08-01

The correlation between the distribution of the intraventricularly (i.v.t.) administered delta agonist [3H](D-ala2,D-leu5)-enkephalin ([3H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [3H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 microns. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of delta opiate receptors, localized within the first 100 microns of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.

Failure of a vagus nerve stimulator following a nearby lightning strike.

Science.gov (United States)

Terry, Garth E; Conry, Joan A; Taranto, Eleanor; Yaun, Amanda

2011-01-01

We recently reported our experience with implanted vagus nerve stimulators (VNS) in 62 children over a 7-year period. Here, we present a case of a VNS that successfully reduced the number and severity of seizures in a patient with an unusual seizure pattern, and failed to function shortly after a lightning storm. To our knowledge, the failure of VNS or any implantable electrical devices by lightning has not been reported in the literature. This mechanism of electrical interference, while unusual, may require more attention as these devices are expected to be used more frequently. Copyright © 2011 S. Karger AG, Basel.

Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

Directory of Open Access Journals (Sweden)

Ryan T Cleary

Full Text Available Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+-K(+-2 Cl(- cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

Science.gov (United States)

Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

2010-01-01

Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two- to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. PMID:16125317

Sulforhodamine 101, a widely used astrocyte marker, can induce cortical seizure-like activity at concentrations commonly used

DEFF Research Database (Denmark)

Rasmussen, Rune; Nedergaard, Maiken; Petersen, Nicolas Caesar

2016-01-01

Sulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in ...

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

Science.gov (United States)

Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2017-05-01

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

Origin and pharmacological response of atrial tachyarrhythmias induced by activation of mediastinal nerves in canines.

Science.gov (United States)

Armour, J Andrew; Richer, Louis-Philippe; Pagé, Pierre; Vinet, Alain; Kus, Teresa; Vermeulen, Michel; Nadeau, Réginald; Cardinal, René

2005-03-31

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Uncaria rhynchophylla and rhynchophylline improved kainic acid-induced epileptic seizures via IL-1β and brain-derived neurotrophic factor.

Science.gov (United States)

Ho, Tin-Yun; Tang, Nou-Ying; Hsiang, Chien-Yun; Hsieh, Ching-Liang

2014-05-15

Uncaria rhynchophylla (UR) has been used for the treatment of convulsions and epilepsy in traditional Chinese medicine. This study reported the major anti-convulsive signaling pathways and effective targets of UR and rhynchophylline (RP) using genomic and immunohistochemical studies. Epileptic seizure model was established by intraperitoneal injection of kainic acid (KA) in rats. Electroencephalogram and electromyogram recordings indicated that UR and RP improved KA-induced epileptic seizures. Toll-like receptor (TLR) and neurotrophin signaling pathways were regulated by UR in both cortex and hippocampus of KA-treated rats. KA upregulated the expression levels of interleukin-1β (IL-1β) and brain-derived neurotrophin factor (BDNF), which were involved in TLR and neurotrophin signaling pathways, respectively. However, UR and RP downregulated the KA-induced IL-1β and BDNF gene expressions. Our findings suggested that UR and RP exhibited anti-convulsive effects in KA-induced rats via the regulation of TLR and neurotrophin signaling pathways, and the subsequent inhibition of IL-1β and BDNF gene expressions. Copyright © 2014 Elsevier GmbH. All rights reserved.

Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: A case-control study

Directory of Open Access Journals (Sweden)

Felix R Montes

2012-01-01

Full Text Available Antifibrinolytic agents are used during cardiac surgery to minimize bleeding and reduce exposure to blood products. Several reports suggest that tranexamic acid (TA can induce seizure activity in the postoperative period. To examine factors associated with postoperative seizures in patients undergoing cardiac surgery who received TA. University-affiliated hospital. Case-control study. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB between January 2008 and December 2009 were identified. During this time, all patients undergoing heart surgery with CPB received TA. Cases were defined as patients who developed seizures that required initiation of anticonvulsive therapy within 48 h of surgery. Exclusion criteria included subjects with preexisting epilepsy and patients in whom the convulsive episode was secondary to a new ischemic lesion on brain imaging. Controls who did not develop seizures were randomly selected from the initial cohort. From an initial cohort of 903 patients, we identified 32 patients with postoperative seizures. Four patients were excluded. Twenty-eight cases and 112 controls were analyzed. Cases were more likely to have a history of renal impairment and higher preoperative creatinine values compared with controls (1.39 ± 1.1 vs. 0.98 ± 0.02 mg/dL, P = 0.02. Significant differences in the intensive care unit, postoperative and total lengths of stay were observed. An association between high preoperative creatinine value and postoperative seizure was identified. TA may be associated with the development of postoperative seizures in patients with renal dysfunction. Doses of TA should be reduced or even avoided in this population.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

International Nuclear Information System (INIS)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

2017-01-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

Energy Technology Data Exchange (ETDEWEB)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

2017-05-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Beta-blocking agents during electroconvulsive therapy: a review.

Science.gov (United States)

Boere, E; Birkenhäger, T K; Groenland, T H N; van den Broek, W W

2014-07-01

Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Exposure to nerve growth factor worsens nephrotoxic effect induced by Cyclosporine A in HK-2 cells.

Directory of Open Access Journals (Sweden)

Donatella Vizza

Full Text Available Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA(NTR and p75(NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 (NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75(NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

Enhanced susceptibility to seizures modulated by high interleukin-1β levels during early life malnutrition.

Science.gov (United States)

Simão, Fabrício; Habekost Oliveira, Victória; Lahorgue Nunes, Magda

2016-10-01

Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1β (IL-1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1β, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1β and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1β and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016. © 2016 Wiley Periodicals, Inc.

Anticonvulsive effect of paeoniflorin on experimental febrile seizures in immature rats: possible application for febrile seizures in children.

Directory of Open Access Journals (Sweden)

Hitomi Hino

Full Text Available Febrile seizures (FS is the most common convulsive disorder in children, but there have been no clinical and experimental studies of the possible treatment of FS with herbal medicines, which are widely used in Asian countries. Paeoniflorin (PF is a major bioactive component of Radix Paeoniae alba, and PF-containing herbal medicines have been used for neuromuscular, neuropsychiatric, and neurodegenerative disorders. In this study, we analyzed the anticonvulsive effect of PF and Keishikashakuyaku-to (KS; a PF-containing herbal medicine for hyperthermia-induced seizures in immature rats as a model of human FS. When immature (P5 male rats were administered PF or KS for 10 days, hyperthermia-induced seizures were significantly suppressed compared to control rats. In cultured hippocampal neurons, PF suppressed glutamate-induced elevation of intracellular Ca(2+ ([Ca(2+](i, glutamate receptor-mediated membrane depolarization, and glutamate-induced neuronal death. In addition, PF partially suppressed the elevation in [Ca(2+](i induced by activation of the metabotropic glutamate receptor 5 (mGluR5, but not that mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA or N-methyl-D-aspartate (NMDA receptors. However, PF did not affect production or release of γ-aminobutyric acid (GABA in hippocampal neurons. These results suggest that PF or PF-containing herbal medicines exert anticonvulsive effects at least in part by preventing mGluR5-dependent [Ca(2+](i elevations. Thus, it could be a possible candidate for the treatment of FS in children.

Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation

International Nuclear Information System (INIS)

Isobe, Ichiro; Maeno, Yoshitaka; Nagao, Masataka; Iwasa, Mineo; Koyama, Hiroyoshi; Seko-Nakamura, Yoshimi; Monma-Ohtaki, Jun

2003-01-01

There are various toxic chemicals that cause cell death. However, in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses are induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response

Directory of Open Access Journals (Sweden)

Tommi Nora

2018-02-01

Full Text Available Deep brain stimulation (DBS of the anterior nucleus of the thalamus (ANT is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient’s seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures

NARCIS (Netherlands)

Thyrion, L.; Raedt, R.; Portelli, J.; van Loo, P.; Wadman, W.J.; Glorieux, G.; Lambrecht, B.N.; Janssens, S.; Vonck, K.; Boon, P.

2016-01-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

Science.gov (United States)

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Optic nerve hypoplasia

Directory of Open Access Journals (Sweden)

Savleen Kaur

2013-01-01

Full Text Available Optic nerve hypoplasia (ONH is a congenital anomaly of the optic disc that might result in moderate to severe vision loss in children. With a vast number of cases now being reported, the rarity of ONH is obviously now refuted. The major aspects of ophthalmic evaluation of an infant with possible ONH are visual assessment, fundus examination, and visual electrophysiology. Characteristically, the disc is small, there is a peripapillary double-ring sign, vascular tortuosity, and thinning of the nerve fiber layer. A patient with ONH should be assessed for presence of neurologic, radiologic, and endocrine associations. There may be maternal associations like premature births, fetal alcohol syndrome, maternal diabetes. Systemic associations in the child include endocrine abnormalities, developmental delay, cerebral palsy, and seizures. Besides the hypoplastic optic nerve and chiasm, neuroimaging shows abnormalities in ventricles or white- or gray-matter development, septo-optic dysplasia, hydrocephalus, and corpus callosum abnormalities. There is a greater incidence of clinical neurologic abnormalities in patients with bilateral ONH (65% than patients with unilateral ONH. We present a review on the available literature on the same to urge caution in our clinical practice when dealing with patients with ONH. Fundus photography, ocular coherence tomography, visual field testing, color vision evaluation, neuroimaging, endocrinology consultation with or without genetic testing are helpful in the diagnosis and management of ONH. (Method of search: MEDLINE, PUBMED.

TRPV1 deletion exacerbates hyperthermic seizures in an age-dependent manner in mice.

Science.gov (United States)

Barrett, Karlene T; Wilson, Richard J A; Scantlebury, Morris H

2016-12-01

Febrile seizures (FS) are the most common seizure disorder to affect children. Although there is mounting evidence to support that FS occur when children have fever-induced hyperventilation leading to respiratory alkalosis, the underlying mechanisms of hyperthermia-induced hyperventilation and links to FS remain poorly understood. As transient receptor potential vanilloid-1 (TRPV1) receptors are heat-sensitive, play an important role in adult thermoregulation and modulate respiratory chemoreceptors, we hypothesize that TRPV1 activation is important for hyperthermia-induced hyperventilation leading to respiratory alkalosis and decreased FS thresholds, and consequently, TRPV1 KO mice will be relatively protected from hyperthermic seizures. To test our hypothesis we subjected postnatal (P) day 8-20 TRPV1 KO and C57BL/6 control mice to heated dry air. Seizure threshold temperature, latency and the rate of rise of body temperature during hyperthermia were assessed. At ages where differences in seizure thresholds were identified, head-out plethysmography was used to assess breathing and the rate of expired CO 2 in response to hyperthermia, to determine if the changes in seizure thresholds were related to respiratory alkalosis. Paradoxically, we observed a pro-convulsant effect of TRPV1 deletion (∼4min decrease in seizure latency), and increased ventilation in response to hyperthermia in TRPV1 KO compared to control mice at P20. This pro-convulsant effect of TRPV1 absence was not associated with an increased rate of expired CO 2 , however, these mice had a more rapid rise in body temperature following exposure to hyperthermia than controls, and the expected linear relationship between body weight and seizure latency was absent. Based on these findings, we conclude that deletion of the TRPV1 receptor prevents reduction in hyperthermic seizure susceptibility in older mouse pups, via a mechanism that is independent of hyperthermia-induced respiratory alkalosis, but

Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.

Science.gov (United States)

Albers, D S; Sonsalla, P K

1995-12-01

Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate

Prophylaxis and Therapy Against Chemical Agents

Science.gov (United States)

2009-11-01

Hematopoietic Consequences F. Dorandeu 5) pH Dependent Toxicity of Sulphur Mustard In Vitro J. Mikler Nerve Agents / Scavengers 1) Mutagenesis...symptoms such as salivation or shortness of breath and lower level exposures could be rendered inconsequential. B.2 CURRENT THERAPY FOR NERVE AGENT

Mechanisms of morphine enhancement of spontaneous seizure activity.

Science.gov (United States)

Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

2007-12-01

High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats.

Science.gov (United States)

Albertson, T E; Walby, W F

1988-01-01

The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and supranthreshold (400 microA) paradigms. Nafimidone (25-50 mg/kg) significantly reduced supranthreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity. The maximum anticonvulsant effectiveness for the 25 mg/kg i.p. dose of nafimidone was seen between 15 and 30 min utilizing a suprathreshold kindling paradigm. Nafimidone did not significantly elevate seizure thresholds at the doses tested; however, nafimidone (3.1-50 mg/kg) reduced the severity and afterdischarge duration of threshold elicited seizures in a non-dose response manner. Drug-induced electroencephalographic spikes were seen in both cortex and amygdala in most kindled rats receiving 100-120 mg/kg i.p. within 30 min of dosing before electrical stimulation. The frequency of spike and wave complexes increased in most of these animals leading to drug-induced spontaneous seizures and death in approximately 25% before electrical stimulation. This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy.

Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice

Directory of Open Access Journals (Sweden)

S Sardari

2011-10-01

Full Text Available "n  Background and purpose of the study: Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ and maximal electroshock (MES seizure tests. "n  Methods: The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p. and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p. or tonic seizures induced by MES (50 mA, 50Hz, 1sec were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. "n  Results: Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. "n  Major conclusion: The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.

Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

Directory of Open Access Journals (Sweden)

Louise A. Mesentier-Louro

2017-01-01

Full Text Available Nerve growth factor (NGF is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC degenerate following optic-nerve crush (ONC, even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

Science.gov (United States)

Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

2017-01-05

Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75 NTR , TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75 NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75 NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

Science.gov (United States)

Li, Jian; Ouyang, Qing; Chen, Cheng-Wen; Chen, Qian-Bo; Li, Xiang-Nan; Xiang, Zheng-Hua; Yuan, Hong-Bin

2017-09-01

Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. β-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of β-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells. © 2017 American Academy of Pain Medicine

Automated seizure detection systems and their effectiveness for each type of seizure.

Science.gov (United States)

Ulate-Campos, A; Coughlin, F; Gaínza-Lein, M; Fernández, I Sánchez; Pearl, P L; Loddenkemper, T

2016-08-01

Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies. Copyright © 2016. Published by Elsevier Ltd.

Anticonvulsant, neuroprotective and behavioral effects of organic and conventional yerba mate (Ilex paraguariensis St. Hil.) on pentylenetetrazol-induced seizures in Wistar rats.

Science.gov (United States)

Branco, Cátia Dos Santos; Scola, Gustavo; Rodrigues, Adriana Dalpicolli; Cesio, Verónica; Laprovitera, Mariajosé; Heinzen, Horacio; Dos Santos, Maitê Telles; Fank, Bruna; de Freitas, Suzana Cesa Vieira; Coitinho, Adriana Simon; Salvador, Mirian

2013-03-01

Epilepsy, which is one of the most common neurological disorders, involves the occurrence of spontaneous and recurrent seizures that alter the performance of the brain and affect several sensory and behavioral functions. Oxidative damage has been associated with post-seizure neuronal injury, thereby increasing an individual's susceptibility to the occurrence of neurodegenerative disorders. The present study investigated the possible anticonvulsive and neuroprotective effects of organic and conventional yerba mate (Ilex paraguariensis), a plant rich in polyphenols, on pentylenetetrazol (PTZ)-induced seizures in Wistar rats. The behavioral and polyphenolic profiles of the yerba mate samples were also evaluated. Infusions of yerba mate (50mg/kg) or distilled water were given to rats for fifteen days by oral gavage. On the 15th day the animals were subjected to open field test, and exploratory behavior was assessed. Subsequently, 60mg/kg PTZ (i.p.) was administered, and animals were observed for the appearance of convulsions for 30min. Latency for the first seizure, tonic-clonic and generalized seizures time, frequency of seizures and mortality induced by PTZ were recorded. The animals were then sacrificed, and the cerebellum, cerebral cortex and hippocampus were quickly removed and frozen to study the neuroprotective effects of yerba mate. The oxidative damage in lipids and proteins, nitric oxide levels, the activities of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat) and non-enzymatic cellular defense (sulfhydryl protein) were quantified in all the tissues. The results showed that organic and conventional yerba mate infusions were able to reduce the frequency of seizures when compared to the PTZ group. Besides, organic yerba mate infusion decreases the tonic-clonic seizures time in relation to the PTZ group. It was also shown that organic and conventional yerba mate infusions reduced the oxidative damage in lipids and proteins and nitric oxide

Oral Uncaria rhynchophylla (UR) reduces kainic acid-induced epileptic seizures and neuronal death accompanied by attenuating glial cell proliferation and S100B proteins in rats.

Science.gov (United States)

Lin, Yi-Wen; Hsieh, Ching-Liang

2011-05-17

Epilepsy is a common clinical syndrome with recurrent neuronal discharges in cerebral cortex and hippocampus. Here we aim to determine the protective role of Uncaria rhynchophylla (UR), an herbal drug belong to Traditional Chinese Medicine (TCM), on epileptic rats. To address this issue, we tested the effect of UR on kainic acid (KA)-induced epileptic seizures and further investigate the underlying mechanisms. Oral UR successfully decreased neuronal death and discharges in hippocampal CA1 pyramidal neurons. The population spikes (PSs) were decreased from 4.1 ± 0.4 mV to 2.1 ± 0.3 mV in KA-induced epileptic seizures and UR-treated groups, respectively. Oral UR protected animals from neuronal death induced by KA treatment (from 34 ± 4.6 to 191.7 ± 48.6 neurons/field) through attenuating glial cell proliferation and S100B protein expression but not GABAA and TRPV1 receptors. The above results provide detail mechanisms underlying the neuroprotective action of UR on KA-induced epileptic seizure in hippocampal CA1 neurons. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Seizure induces activation of multiple subtypes of neural progenitors and growth factors in hippocampus with neuronal maturation confined to dentate gyrus

Energy Technology Data Exchange (ETDEWEB)

Indulekha, Chandrasekharan L.; Sanalkumar, Rajendran [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India); Thekkuveettil, Anoopkumar [Molecular Medicine, Biomedical Technology Wing, Sree Chitra Thirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala (India); James, Jackson, E-mail: jjames@rgcb.res.in [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India)

2010-03-19

Adult hippocampal neurogenesis is altered in response to different physiological and pathological stimuli. GFAP{sup +ve}/nestin{sup +ve} radial glial like Type-1 progenitors are considered to be the resident stem cell population in adult hippocampus. During neurogenesis these Type-1 progenitors matures to GFAP{sup -ve}/nestin{sup +ve} Type-2 progenitors and then to Type-3 neuroblasts and finally differentiates into granule cell neurons. In our study, using pilocarpine-induced seizure model, we showed that seizure initiated activation of multiple progenitors in the entire hippocampal area such as DG, CA1 and CA3. Seizure induction resulted in activation of two subtypes of Type-1 progenitors, Type-1a (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup +ve}) and Type-1b (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup -ve}). We showed that majority of Type-1b progenitors were undergoing only a transition from a state of dormancy to activated form immediately after seizures rather than proliferating, whereas Type-1a showed maximum proliferation by 3 days post-seizure induction. Type-2 (GFAP{sup -ve}/nestin{sup +ve}/BrdU{sup +ve}) progenitors were few compared to Type-1. Type-3 (DCX{sup +ve}) progenitors showed increased expression of immature neurons only in DG region by 3 days after seizure induction indicating maturation of progenitors happens only in microenvironment of DG even though progenitors are activated in CA1 and CA3 regions of hippocampus. Also parallel increase in growth factors expression after seizure induction suggests that microenvironmental niche has a profound effect on stimulation of adult neural progenitors.

Curcumin inhibits amygdaloid kindled seizures in rats.

Science.gov (United States)

DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

2009-06-20

Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

Deep Recurrent Neural Networks for seizure detection and early seizure detection systems

Energy Technology Data Exchange (ETDEWEB)

Talathi, S. S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2017-06-05

Epilepsy is common neurological diseases, affecting about 0.6-0.8 % of world population. Epileptic patients suffer from chronic unprovoked seizures, which can result in broad spectrum of debilitating medical and social consequences. Since seizures, in general, occur infrequently and are unpredictable, automated seizure detection systems are recommended to screen for seizures during long-term electroencephalogram (EEG) recordings. In addition, systems for early seizure detection can lead to the development of new types of intervention systems that are designed to control or shorten the duration of seizure events. In this article, we investigate the utility of recurrent neural networks (RNNs) in designing seizure detection and early seizure detection systems. We propose a deep learning framework via the use of Gated Recurrent Unit (GRU) RNNs for seizure detection. We use publicly available data in order to evaluate our method and demonstrate very promising evaluation results with overall accuracy close to 100 %. We also systematically investigate the application of our method for early seizure warning systems. Our method can detect about 98% of seizure events within the first 5 seconds of the overall epileptic seizure duration.

Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

Science.gov (United States)

Qureshi, Itefaq Hussain; Riaz, Azra; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

2017-08-01

Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

Effect of prophylactic phenobarbital on seizures, encephalopathy ...

African Journals Online (AJOL)

cerebral metabolism and re-oxygenation, which lead to cerebral oedema .... their serum electrolytes and glucose, calcium and magnesium levels measured. ..... Dzhala V, Ben-Ari Y, Khazipov R. Seizures accelerate anoxia-induced neuronal.

Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats.

Science.gov (United States)

Gerbi, A; Maixent, J M; Ansaldi, J L; Pierlovisi, M; Coste, T; Pelissier, J F; Vague, P; Raccah, D

1999-01-01

Diabetic neuropathy has been associated with a decrease in nerve conduction velocity, Na,K-ATPase activity and characteristic histological damage of the sciatic nerve. The aim of this study was to evaluate the potential effect of a dietary supplementation with fish oil [(n-3) fatty acids] on the sciatic nerve of diabetic rats. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (n = 20) were fed a nonpurified diet supplemented with either olive oil (DO) or fish oil (DM), and control animals (n = 10) were fed a nonpurified diet supplemented with olive oil at a daily dose of 0.5 g/kg by gavage for 8 wk. Nerves were characterized by their conduction velocity, morphometric analysis and membrane Na, K-ATPase activity. Nerve conduction velocity, as well as Na,K-ATPase activity, was improved by fish oil treatment. A correlation was found between these two variables (R = 0.999, P < 0.05). Moreover, a preventive effect of fish oil was observed on nerve histological damage [endoneurial edema, axonal degeneration (by 10-15%) with demyelination]. Moreover, the normal bimodal distribution of the internal diameter of myelinated fibers was absent in the DO group and was restored in the DM group. These data suggest that fish oil therapy may be effective in the prevention of diabetic neuropathy.

Distribution of elements and water in peripheral nerve of streptozocin-induced diabetic rats

International Nuclear Information System (INIS)

Lowery, J.M.; Eichberg, J.; Saubermann, A.J.; LoPachin, R.M. Jr.

1990-01-01

Accumulating evidence suggests that alterations in Na, Ca, K, and other biologically relevant elements play a role in the mechanism of cell injury. The pathogenesis of experimental diabetic neuropathy is unknown but might include changes in the distribution of these elements in morphological compartments. In this study, this possibility was examined via electron-probe X-ray microanalysis to measure both concentrations of elements (millimoles of element per kilogram dry or wet weight) and cell water content (percent water) in frozen, unfixed, unstained sections of peripheral nerve from control and streptozocin-induced diabetic rats. Our results indicate that after 20 wk of experimental diabetes, mitochondria and axoplasm from myelinated axons of proximal sciatic nerve displayed diminished K and Cl content, whereas in tibial nerve, the intraaxonal levels of these elements increased. In distal sciatic nerve, mitochondrial and axoplasmic levels of Ca were increased, whereas other elemental alterations were not observed. These regional changes resulted in a reversal of the decreasing proximodistal concentration gradients for K and Cl, which exist in nondiabetic rat sciatic nerve. Our results cannot be explained on the basis of altered water. Highly distinctive changes in elemental distribution observed might be a critical component of the neurotoxic mechanism underlying diabetic neuropathy

Metabolic and toxic causes of canine seizure disorders: A retrospective study of 96 cases.

Science.gov (United States)

Brauer, Christina; Jambroszyk, Melanie; Tipold, Andrea

2011-02-01

A wide variety of intoxications and abnormal metabolic conditions can lead to reactive seizures in dogs. Patient records of dogs suffering from seizure disorders (n=877) were reviewed, and 96 cases were associated with an underlying metabolic or toxic aetiology. These included intoxications by various agents, hypoglycaemia, electrolyte disorders, hepatic encephalopathy, hypothyroidism, uraemic encephalopathy, hypoxia and hyperglycaemia. The incidence of the underlying diseases was determined. The most common causes of reactive seizures were intoxications (39%, 37 dogs) and hypoglycaemia (32%, 31 dogs). Hypocalcaemia was the most frequent electrolyte disorder causing reactive seizures (5%) and all five of these dogs had ionised calcium concentrations ≤0.69 mmol/L. Eleven per cent of dogs with seizures had metabolic or toxic disorders and this relatively high frequency emphasises the importance of a careful clinical work-up of cases presented with seizures in order to reach a correct diagnosis and select appropriate treatment options. Copyright © 2009 Elsevier Ltd. All rights reserved.

Seizures

Science.gov (United States)

... may be diagnosed with epilepsy , also known as seizure disorder. Seizure Basics Usually, electrical activity in the brain involves ... times. Fortunately, fainting rarely is a sign of epilepsy. Most kids recover very quickly (seconds to minutes) ...

Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

Science.gov (United States)

Jain, Vivek; Pareek, Ashutosh; Paliwal, Nishant; Ratan, Yashumati; Jaggi, Amteshwar Singh; Singh, Nirmal

2014-02-01

This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

Phénomènes neuro-inflammatoires au cours de l'état de mal épileptique induit par le soman. Correction par des combinaisons atropine-kétamine.

OpenAIRE

Dhote , Franck

2010-01-01

Epileptic seizures, status epilepticus (SE) and seizure-related brain damage (SRBD) due to organophosphorus nerve agent (OP) poisoning are accompanied by neuro-inflammatory events whose role in SRBD is not clear. Antagonists of the glutamatergic receptor NMDA, such as ketamine (KET), proved to be antiepileptic and neuroprotective even when SE is refractory to benzodiazepines 10 to 20 min after the initiation of seizures. Moreover, peripheral anti-inflammatory properties of KET have been descr...

Recurrent Isolated Oculomotor Nerve Palsy after Radiation of a Mesencephalic Metastasis. Case Report and Mini Review

Science.gov (United States)

Grabau, Olga; Leonhardi, Jochen; Reimers, Carl D.

2014-01-01

Introduction: Recurrent oculomotor nerve palsies are extremely rare clinical conditions. Case report: Here, we report on a unique case of a short-lasting recurrent unilateral incomplete external and complete internal oculomotor nerve palsy. The episodic palsies were probably caused by an ipsilateral mesencephalic metastasis of a breast carcinoma and occurred after successful brain radiation therapy. Discussion: While the pathogenic mechanism remains unclear, the recurrent sudden onset and disappearance of the palsies and their decreasing frequency after antiepileptic treatment suggest the occurrence of epilepsy-like brainstem seizures. A review of case reports of spontaneous reversible oculomotor nerve palsies is presented. PMID:25104947

Recurrent isolated oculomotor nerve palsy after radiation of a mesencephalic metastasis. Case report and mini-review.

Directory of Open Access Journals (Sweden)

Olga eGrabau

2014-07-01

Full Text Available Introduction: Recurrent oculomotor nerve palsies are extremely rare clinical conditions. Case report: Here, we report on a unique case of a short-lasting recurrent unilateral incomplete external and complete internal oculomotor nerve palsy. The episodic palsies were probably caused by an ipsilateral mesencephalic metastasis of a breast carcinoma and occurred after successful brain radiation therapy. Discussion: While the pathogenic mechanism remains unclear, the recurrent sudden onset and disappearance of the palsies and their decreasing frequency after antiepileptic treatment suggest the occurrence of epilepsy-like brainstem seizures. A review of case reports of spontaneous reversible oculomotor nerve palsies is presented.

Inhibition of mitochondrial complex I in cerebral cortex of immature rats following seizures induced by homocysteic acid

Czech Academy of Sciences Publication Activity Database

Ješina, P.; Folbergrová, Jaroslava; Drahota, Zdeněk; Haugvicová, Renata; Lisá, Věra; Pecinová, Alena; Houštěk, Josef

2008-01-01

Roč. 31, Suppl.1 (2008), s. 60-60 ISSN 0141-8955. [Annual Symposium of the Society for the Study of Inborn Errors of Metabolism . 02.09.2008-05.09.2008, Lisboa] R&D Projects: GA ČR GA309/08/0292 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * immature rats * homocysteic acid-induced seizures * mitochondrial complex I inhibition Subject RIV: CE - Biochemistry

Seizures

Science.gov (United States)

... wake up between them. Seizures can have many causes, including medicines, high fevers, head injuries and certain diseases. People who have recurring seizures due to a brain disorder have epilepsy. NIH: National Institute of Neurological Disorders and Stroke

Gamma knife irradiation of injured sciatic nerve induces histological and behavioral improvement in the rat neuropathic pain model.

Directory of Open Access Journals (Sweden)

Yuki Yagasaki

Full Text Available We examined the effects of gamma knife (GK irradiation on injured nerves using a rat partial sciatic nerve ligation (PSL model. GK irradiation was performed at one week after ligation and nerve preparations were made three weeks after ligation. GK irradiation is known to induce immune responses such as glial cell activation in the central nervous system. Thus, we determined the effects of GK irradiation on macrophages using immunoblot and histochemical analyses. Expression of Iba-1 protein, a macrophage marker, was further increased in GK-treated injured nerves as compared with non-irradiated injured nerves. Immunohistochemical study of Iba-1 in GK-irradiated injured sciatic nerves demonstrated Iba-1 positive macrophage accumulation to be enhanced in areas distal to the ligation point. In the same area, myelin debris was also more efficiently removed by GK-irradiation. Myelin debris clearance by macrophages is thought to contribute to a permissive environment for axon growth. In the immunoblot study, GK irradiation significantly increased expressions of βIII-tubulin protein and myelin protein zero, which are markers of axon regeneration and re-myelination, respectively. Toluidine blue staining revealed the re-myelinated fiber diameter to be larger at proximal sites and that the re-myelinated fiber number was increased at distal sites in GK-irradiated injured nerves as compared with non-irradiated injured nerves. These results suggest that GK irradiation of injured nerves facilitates regeneration and re-myelination. In a behavior study, early alleviation of allodynia was observed with GK irradiation in PSL rats. When GK-induced alleviation of allodynia was initially detected, the expression of glial cell line-derived neurotrophic factor (GDNF, a potent analgesic factor, was significantly increased by GK irradiation. These results suggested that GK irradiation alleviates allodynia via increased GDNF. This study provides novel evidence that GK

Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures.

Science.gov (United States)

Töllner, Kathrin; Twele, Friederike; Löscher, Wolfgang

2016-04-01

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

[Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].

Science.gov (United States)

Shan, Ying; Qin, Jiong; Chang, Xing-zhi; Yang, Zhi-xian

2004-04-01

The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage. Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons. In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P seizure, it could lighten the brain damage resulted from repeated FS to some extent.

Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

LENUS (Irish Health Repository)

Costello, Richard W

2012-02-01

The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

LENUS (Irish Health Repository)

Costello, Richard W

2011-05-01

The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

Diazepam prophylaxis of contrast media-induced seizures during computed tomography of patients with brain metastases

International Nuclear Information System (INIS)

Pagani, J.J.; Hayman, L.A.; Bigelow, R.H.; Libshitz, H.I.; Lepke, R.A.; Wallace, S.

1983-01-01

The effect of 5 mg of intravenous diazepam (Valium) on contrast media-associated seizer incidence was studied in a randomized controlled trial involving 284 patients with known or suspected brain metastases undergoing cerebral computed tomography. Of these patients, 188 were found to have brain metastases, and it is estimated that for this subgroup prophylactic diazepam reduces the risk of contrast-assocated seizure by a factor of 0.26. Seizures occurred in three of 96 patients with metastases on diazepam and in 14 of 92 patients with metastases but without diazepam. Factors related to increased risk of contrast media-associated seizures are: (1) prior seizure history due to brain metatases and/or prior contrast, (2) progressive cerebral metastases, and (3) prior or concurrent brain antineoplastic therapy. Factors not related to an increased risk of these seizures are: (1) contrast media dosage, chemical composition, or osmolarity, (2) computed tomographic appearance of metastases, and (3) type of primary malignancy. Concomitant therapeutic levels of diphenylhydantoin (Dilantin) do not protect completely against contrast media-associated seizures. Pathophysiology of contrast media-associated seizures is discussed in view of the risk factors determined by this study

Antiseizure Effects of Ketogenic Diet on Seizures Induced with ...

African Journals Online (AJOL)

olayemitoyin

experimental data in Nigeria on the usefulness of KD in epilepsy models. This is ... Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. ..... in animal occurs through the inhibition of GABA.

Cocaine-Associated Seizures and Incidence of Status Epilepticus

Directory of Open Access Journals (Sweden)

Majlesi, Nima DO

2010-05-01

Full Text Available Objectives: Acute complications from cocaine abuse are commonly treated in the emergency department (ED; one of the most consequential is status epilepticus. The incidence of this complication is not clearly defined in the prior literature on cocaine-associated sequelae. We evaluated the incidence of status epilepticus in patients with seizures secondary to suspected cocaine use.Methods: We performed a retrospective multi-center study of patients with seizures resulting from cocaine use. We identified study subjects at 15 hospitals by record review and conducted a computer-assisted records search to identify patients with seizures for each institution over a four-year period. We selected subjects from this group on the basis of cocaine use and determined the occurrence of status epilepticus among them. Data were collected on each subject using a standardized data collection form.Results: We evaluated 43 patients in the ED for cocaine-associated seizures. Their age range was 17 to 54, with a mean age was 31 years; 53% were male. Of 43 patients, 42 experienced a single tonic-clonic seizure and one developed status epilepticus. All patients had either a history of cocaine use or positive urine drug screen for cocaine.Conclusion: Despite reported cases of status epilepticus with cocaine-induced seizures, the incidence of this complication was unclear based on prior literature. This study shows that most cocaine-associated seizures are self-limited. [West J Emerg Med. 2010; 11(2:157-160.

Effect of carbamazepine (Tegretol) on seizure and EEG patterns in monkeys with alumina-induced focal motor and hippocampal foci.

Science.gov (United States)

David, J; Grewal, R S

1976-12-01

Qualitative and quantitative aspects of chronic carbamazepine (Tegretol) medication on focal seizures and associated interictal EEG abnormalities in Rhesus monkeys with alumina-induced foci in either the sensorimotor cortex or the hipocampus was investigated. In both groups of animals, carbamazepine produced qualitative control of visible seizures and reduced intracortical spike propagation, but did not cause complete normalization of the background EEG; quantitative indices, such as spike density and amount of paroxysmal discharge representative of abnormal EEG activity, were significantly reduced with respect to predrug values during medication and after cessation as well. Threshold to pentylenetetrazol was elevated by carbamazepine in both groups of epileptic monkeys. Aggressivity and other clinical manifestations in monekys with hippocampal foci were markedly reduced by carbamazepine.

Inhibition of the prostaglandin E2 receptor EP2 prevents status epilepticus-induced deficits in the novel object recognition task in rats

Science.gov (United States)

Rojas, Asheebo; Ganesh, Thota; Manji, Zahra; O’neill, Theon; Dingledine, Raymond

2016-01-01

Survivors of exposure to an organophosphorus nerve agent may develop a number of complications including long-term cognitive deficits (Miyaki et al., 2005; Nishiwaki et al., 2001). We recently demonstrated that inhibition of the prostaglandin E2 receptor, EP2, attenuates neuroinflammation and neurodegeneration caused by status epilepticus (SE) induced by the soman analog, diisopropylfluorophosphate (DFP), which manifest within hours to days of the initial insult. Here, we tested the hypothesis that DFP exposure leads to a loss of cognitive function in rats that is blocked by early, transient EP2 inhibition. Adult male Sprague-Dawley rats were administered vehicle or the competitive EP2 antagonist, TG6-10-1, (ip) at various times relative to DFP-induced SE. DFP administration resulted in prolonged seizure activity as demonstrated by cortical electroencephalography (EEG). A single intraperitoneal injection of TG6-10-1 or vehicle 1 h prior to DFP did not alter the development of seizures, the latency to SE or the duration of SE. Rats administered six injections of TG6-10-1 starting 90 min after the onset of DFP-induced SE could discriminate between a novel and familiar object 6–12 weeks after SE, unlike vehicle treated rats which showed no preference for the novel object. By contrast, behavioral changes in the light-dark box and open field assays were not affected by TG6-10-1. Delayed mortality after DFP was also unaffected by TG6-10-1. Thus, selective inhibition of the EP2 receptor may prevent SE-induced memory impairment in rats caused by exposure to a high dose of DFP. PMID:27477533

Imaging seizure activity: a combined EEG/EMG-fMRI study in reading epilepsy.

Science.gov (United States)

Salek-Haddadi, Afraim; Mayer, Thomas; Hamandi, Khalid; Symms, Mark; Josephs, Oliver; Fluegel, Dominique; Woermann, Friedrich; Richardson, Mark P; Noppeney, Uta; Wolf, Peter; Koepp, Matthias J

2009-02-01

To characterize the spatial relationship between activations related to language-induced seizure activity, language processing, and motor control in patients with reading epilepsy. We recorded and simultaneously monitored several physiological parameters [voice-recording, electromyography (EMG), electrocardiography (ECG), electroencephalography (EEG)] during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in nine patients with reading epilepsy. Individually tailored language paradigms were used to induce and record habitual seizures inside the MRI scanner. Voxel-based morphometry (VBM) was used for structural brain analysis. Reading-induced seizures occurred in six out of nine patients. One patient experienced abundant orofacial reflex myocloni during silent reading in association with bilateral frontal or generalized epileptiform discharges. In a further five patients, symptoms were only elicited while reading aloud with self-indicated events. Consistent activation patterns in response to reading-induced myoclonic seizures were observed within left motor and premotor areas in five of these six patients, in the left striatum (n = 4), in mesiotemporal/limbic areas (n = 4), in Brodmann area 47 (n = 3), and thalamus (n = 2). These BOLD activations were overlapping or adjacent to areas physiologically activated during language and facial motor tasks. No subtle structural abnormalities common to all patients were identified using VBM, but one patient had a left temporal ischemic lesion. Based on the findings, we hypothesize that reflex seizures occur in reading epilepsy when a critical mass of neurons are activated through a provoking stimulus within corticoreticular and corticocortical circuitry subserving normal functions.

Development of a mouse model of neuropathic pain following photochemically induced ischemia in the sciatic nerve.

Science.gov (United States)

Hao, J X; Blakeman, K H; Yu, W; Hultenby, K; Xu, X J; Wiesenfeld-Hallin, Z

2000-05-01

A mouse model of neuropathic pain was developed by a photochemically induced ischemic nerve injury in normal male C57/BL6 mice. The ischemia was induced by unilateral irradiation of the sciatic nerve with an argon ion laser after intravenous administration of a photosensitizing dye, erythrosin B. The nerve injury resulted in a significant decrease in withdrawal threshold of the hindpaws to mechanical stimulation with von Frey hairs, as well as increased responsiveness to cold and heat stimulation. The mice, however, did not exhibit overt spontaneous pain-like behaviors. The evoked pain-related behaviors were observed bilaterally, although the ipsilateral changes were greater than on the contralateral side. The extent and time course of the behavioral changes were related to the duration of laser irradiation, with 1-min exposure producing the most consistent effect. Morphological examination at the light microscopic level revealed partial demyelination and axonal degeneration of the large myelinated fibers at the epicenter of the lesion 1 week postirradiation. The extent of the damage was correlated with the duration of irradiation. Injury and loss of unmyelinated fibers were also observed at the electronmicroscopic level. We conclude that an intravascular photochemical reaction leading to ischemia results in graded damage to the sciatic nerve in mice. Moreover, the nerve injury is associated with the development of abnormal pain-related behaviors. Both the behavioral and the morphological changes are correlated with the duration of irradiation. These results establish a mouse model of partial nerve injury with neuropathic pain-like behaviors which may be useful in studies using genetically modified mice. Copyright 2000 Academic Press.

Biomaterials for mediation of chemical and biological warfare agents.

Science.gov (United States)

Russell, Alan J; Berberich, Jason A; Drevon, Geraldine F; Koepsel, Richard R

2003-01-01

Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.

After-discharges and seizures during pediatric extra-operative electrical cortical stimulation functional brain mapping: Incidence, thresholds, and determinants.

Science.gov (United States)

Aungaroon, Gewalin; Zea Vera, Alonso; Horn, Paul S; Byars, Anna W; Greiner, Hansel M; Tenney, Jeffrey R; Arthur, Todd M; Crone, Nathan E; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

2017-10-01

This study examined the incidence, thresholds, and determinants of electrical cortical stimulation (ECS)-induced after-discharges (ADs) and seizures. Electrocorticograph recordings were reviewed to determine incidence of ECS-induced ADs and seizures. Multivariable analyses for predictors of AD/seizure occurrence and their thresholds were performed. In 122 patients, the incidence of ADs and seizures was 77% (94/122) and 35% (43/122) respectively. Males (odds ratio [OR] 2.92, 95% CI 1.21-7.38, p=0.02) and MRI-negative patients (OR 3.69, 95% CI 1.24-13.7, p=0.03) were found to have higher odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient -0.151, 95% CI -0.267 to -0.035, p=0.011). ECS-induced seizures were more likely in patients with lateralized functional imaging (OR 6.62, 95% CI 1.36-55.56, p=0.036, for positron emission tomography) and presence of ADs (OR 3.50, 95% CI 1.12-13.36, p=0.043). ECS is associated with a high incidence of ADs and seizures. With age, current thresholds decrease and the probability for AD/seizure occurrence increases. ADs and seizures during ECS brain mapping are potentially hazardous and affect its functional validity. Thus, safer method(s) for brain mapping with improved neurophysiologic validity are desirable. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Intraoperative seizures and seizures outcome in patients underwent awake craniotomy.

Science.gov (United States)

Yuan, Yang; Peizhi, Zhou; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shu, Jiang; Qing, Mao

2016-11-25

Awake craniotomies (AC) could reduce neurological deficits compared with patients under general anesthesia, however, intraoperative seizure is a major reason causing awake surgery failure. The purpose of the study was to give a comprehensive overview the published articles focused on seizure incidence in awake craniotomy. Bibliographic searches of the EMBASE, MEDLINE,were performed to identify articles and conference abstracts that investigated the intraoperative seizure frequency of patients underwent AC. Twenty-five studies were included in this meta-analysis. Among the 25 included studies, one was randomized controlled trials and 5 of them were comparable studies. The pooled data suggested the general intraoperative seizure(IOS) rate for patients with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for glioma patients was 8% and low grade patients was 10%. The pooled data showed early seizure rates of AC patients was 11% and late seizure rates was 35%. This systematic review and meta-analysis shows that awake craniotomy is a safe technique with relatively low intraoperative seizure occurrence. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

Chlorpromazine-induced status epilepticus: A case report

Directory of Open Access Journals (Sweden)

Momčilović-Kostadinović Dragana

2013-01-01

Full Text Available Introduction. It is largely known that some antipsychotic agents could have proconvulsive and proepileptogenic effects in some patients and could induce EEG abnormalities as well. However, the association of status epilepticus with certain antipsychotic drugs has been very rarely reported. Case Report. A case of an 18-year-old adolescent girl, with chlorpromazine therapy started for anxiety-phobic disorder was reported. Her personal history disclosed delayed psychomotor development. Shortly after the introduction of the neuroleptic chlorpromazine therapy in minimal daily dose (37.5 mg, she developed myoclonic status epilepticus, confirmed by the EEG records. Frequent, symmetrical bilateral myoclonic jerks and altered behavior were associated with bilateral epileptiform discharges of polyspikes and spike-wave complexes. This epileptic event lasted 3.5 hours and it was stopped by the parenteral administration of valproate and lorazepam; she was EEG monitored until stable remission. Status epilepticus as initial epileptic event induced by neuroleptic agent was not previously reported in our national literature. Conclusion. Introduction of chlorpromazine to a patient without history of seizures is associated with the evolution of an epileptic activity, including the occurrence of status epilepticus. Clinical evaluation of the risk factors possibly related to chlorpromazine-induced seizure is recommended in individual patients before administering this drug.

Significance and nature of bystander responses induced by various agents.

Science.gov (United States)

Verma, Neha; Tiku, Ashu Bhan

2017-07-01

Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanism of RDX-Induced Seizures in Rats

Science.gov (United States)

2009-09-01

benchmark for RDX. d. The main acute effect of RDX after ingestion of high doses is the induction of seizures accompanied by excessive salivation ...most animals that seize demonstrate excessive salivation (Schneider et al., 1977; Burdette et al., 1988; Crouse et al., 2006). These clinical signs...Padilla et al., 1998). A 2% (wet wt./vol.) homogenate was made in 0.1 M Na phosphate buffer ( pH 8.0) + 1% Triton, using a 20 sec burst (on ice) of

Electric Stimulation of Ear Reduces the Effect of Toll-Like Receptor 4 Signaling Pathway on Kainic Acid-Induced Epileptic Seizures in Rats

Directory of Open Access Journals (Sweden)

En-Tzu Liao

2018-01-01

Full Text Available Epilepsy is a common clinical syndrome with recurrent neuronal discharges in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or of little benefit in 30% of epileptic patients and usually cause severe side effects. Emerging evidence indicates the crucial role of inflammatory mediators in epilepsy. The current study investigates the role of toll-like receptor 4 (TLR4 and its underlying mechanisms in kainic acid- (KA- induced epileptic seizures in rats. Experimental KA injection successfully initiated an epileptic seizure accompanied by increased expression of TLR4 in the prefrontal cortex, hippocampus, and somatosensory cortex. In addition, calcium-sensitive phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα increased after the initiation of the epileptic seizure. Furthermore, downstream-phosphorylated signal-regulated kinase (ERK, c-Jun NH2-terminal protein kinase (JNK, and p38 kinase simultaneously increased in these brain areas. Moreover, the transcriptional factor phosphorylated nuclear factor-κB (pNF-κB increased, suggesting that nucleus transcription was affected. Furthermore, the aforementioned molecules decreased by an electric stimulation (ES of either 2 Hz or 15 Hz of the ear in the three brain areas. Accordingly, we suggest that ES of the ear can successfully control epileptic seizures by regulating the TLR4 signaling pathway and has a therapeutic benefit in reducing epileptic seizures.

Anticonvulsant and neuroprotective effect of (S)-3,4-dicarboxyphenylglycine against seizures induced in immature rats by homocysteic acid

Czech Academy of Sciences Publication Activity Database

Folbergrová, Jaroslava; Druga, Rastislav; Haugvicová, Renata; Mareš, Pavel; Otáhal, Jakub

2008-01-01

Roč. 54, č. 4 (2008), s. 665-675 ISSN 0028-3908 R&D Projects: GA ČR GA309/02/1238; GA ČR(CZ) GA309/05/2015 Institutional research plan: CEZ:AV0Z50110509 Keywords : DL-homocysteic acid induced seizures * mGluR8 agonist (S)-3,4-DCPG * protection Subject RIV: FH - Neurology Impact factor: 3.383, year: 2008

Seizure development after stroke.

Science.gov (United States)

Misirli, H; Ozge, A; Somay, G; Erdoğan, N; Erkal, H; Erenoğlu, N Y

2006-12-01

Although there have been many studies on seizures following stroke, there is still much we do not know about them. In this study, we evaluated the characteristics of seizures in stroke patients. There were 2267 patients with a first-ever stroke, and after excluding 387 patients, 1880 were available for analysis. Of these 1880 patients, we evaluated 200 patients with seizures and 400 patients without seizures. We investigated the seizures according to age, gender, stroke type, the aetiology of ischaemic stroke and the localisation of the lesion. The seizures were classified as early onset and late onset and the seizure type as partial, generalised or secondarily generalised. Seizures occurred in 200 (10.6%) of 1880 strokes. The number of patients with seizures were 138 (10.6%) in ischaemic stroke group and 62 (10.7%) in haemorrhagic stroke group. Patients with ischaemic strokes had 41 embolic (29.7%) and 97 thrombotic (70.3%) origin, and these were not statistically significant in comparison with controls. Cortical involvement for the development of seizures was the most important risk factor (odds ratios = 4.25, p < 0.01). It was concluded that embolic strokes, being younger than 65 years old, and cortical localisation of stroke were important risks for developing seizures.

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

Science.gov (United States)

Urrego, Diana; Múnera, Alejandro; Troncoso, Julieta

2011-01-01

Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

The effect of propofol-remifentanil anesthesia on selected seizure quality indices in electroconvulsive therapy.

Science.gov (United States)

Dinwiddie, Stephen H; Glick, David B; Goldman, Morris B

2012-07-01

Use of a short-acting opiate to potentiate anesthetic induction agents has been shown to increase seizure duration in electroconvulsive therapy (ECT), but little is known of the effect of this combination on indices of seizure quality. To determine whether anesthetic modality affects commonly provided indices of seizure quality. Twenty-five subjects were given propofol 2 mg/kg body weight for their first ECT session, at which time seizure threshold was titrated. Subjects thereafter alternated between that anesthetic regimen or propofol 0.5 mg/kg plus remifentanil 1 mcg/kg. Linear mixed models with random subject effect, adjusting for electrode placement, electrical charge, and number of treatments, were fit to estimate effect of anesthesia on seizure duration and several standard seizure quality indices (average seizure energy, time to peak electroencephalography (EEG) power, maximum sustained power, interhemispheric coherence, early and midictal EEG amplitude, and maximum sustained interhemispheric EEG coherence). Propofol-remifentanil anesthesia significantly lengthened seizure duration and was associated with longer time to reach maximal EEG power and coherence as well as maximal degree of interhemispheric EEG coherence. No effect was seen on early ictal amplitude or average seizure energy index. Propofol-remifentanil anesthesia prolongs seizure duration and has a significant effect on some, but not all, measures of seizure quality. This effect may be of some benefit in cases where adequate seizures are otherwise difficult to elicit. Varying anesthetic technique may allow more precise investigation of the relationships between and relative impacts of commonly used seizure quality indices on clinical outcomes and ECT-related cognitive side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a kainate-induced seizure.

Directory of Open Access Journals (Sweden)

Yuki Sugiura

Full Text Available We report the use of matrix-assisted laser desorption/ionization (MALDI imaging mass spectrometry combined with capillary electrophoresis (CE mass spectrometry to visualize energy metabolism in the mouse hippocampus by imaging energy-related metabolites. We show the distribution patterns of ATP, ADP, and AMP in the hippocampus as well as changes in their amounts and distribution patterns in a murine model of limbic, kainate-induced seizure. As an acute response to kainate administration, we found massive and moderate reductions in ATP and ADP levels, respectively, but no significant changes in AMP levels--especially in cells of the CA3 layer. The results suggest the existence of CA3 neuron-selective energy metabolism at the anhydride bonds of ATP and ADP in the hippocampal neurons during seizure. In addition, metabolome analysis of energy synthesis pathways indicates accelerated glycolysis and possibly TCA cycle activity during seizure, presumably due to the depletion of ATP. Consistent with this result, the observed energy depletion significantly recovered up to 180 min after kainate administration. However, the recovery rate was remarkably low in part of the data-pixel population in the CA3 cell layer region, which likely reflects acute and CA3-selective neural death. Taken together, the present approach successfully revealed the spatiotemporal energy metabolism of the mouse hippocampus at a cellular resolution--both quantitatively and qualitatively. We aim to further elucidate various metabolic processes in the neural system.

Association of Periodic and Rhythmic Electroencephalographic Patterns With Seizures in Critically Ill Patients.

Science.gov (United States)

Rodriguez Ruiz, Andres; Vlachy, Jan; Lee, Jong Woo; Gilmore, Emily J; Ayer, Turgay; Haider, Hiba Arif; Gaspard, Nicolas; Ehrenberg, J Andrew; Tolchin, Benjamin; Fantaneanu, Tadeu A; Fernandez, Andres; Hirsch, Lawrence J; LaRoche, Suzette

2017-02-01

Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear. To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures. We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures. Continuous electroencephalography. Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures. Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10). In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with

Evaluation of effects of dichloromethane fraction from Platonia insignis on pilocarpine-induced seizures

Directory of Open Access Journals (Sweden)

Joaquim S. da Costa Júnior

2011-09-01

Full Text Available The objective of present study was to evaluate the antioxidant and anticonvulsant activities of dichloromethane fraction (DMF from Platonia insignis Mart., Clusiaceae. The DMF from P. insignis (2 mg/kg was tested by intraperitoneal (i.p. to evaluate effects on lipid peroxidation level, nitrite formation, as well as on locomotor and anticonvulsant activities. Wistar rats were treated with, (saline/Tween 80 0.5%, i.p., control group, DMF (2 mg/kg, i.p., DMF group, pilocarpine (400 mg/kg, i.p., P400 group, or the combination of DMF (2 mg/kg, i.p. and pilocarpine (400 mg/kg, i.p., DMF plus P400. After the treatments all groups were observed for 24 h. In P400 group rats there was a decrease in the motor activity when compared with control group. In DMF plus P400 co-administered rats was observed an increase in motor activity when compared with P400 group. In P400 group rats there was a significant increase in lipid peroxidation and nitrite levels. In DMF plus P400 co-administered rats, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content after seizures. Previous findings strongly support the hypothesis that oxidative stress occurs in rat striatum during pilocarpine-induced seizures, and our results imply that strong neuprotective effect on this brain region could be achieved using DMF from P. insignis.

Athletes with seizure disorders.

Science.gov (United States)

Knowles, Byron Don; Pleacher, Michael D

2012-01-01

Individuals with seizure disorders have long been restricted from participation in certain sporting activities. Those with seizure disorders are more likely than their peers to have a sedentary lifestyle and to develop obesity. Regular participation in physical activity can improve both physical and psychosocial outcomes for persons with seizure disorders. Seizure activity often is reduced among those patients who regularly engage in aerobic activity. Recent literature indicates that the diagnosis of seizure disorders remains highly stigmatizing in the adolescent population. Persons with seizure disorders may be more accepted by peer groups if they are allowed to participate in sports and recreational activities. Persons with seizure disorders are encouraged to participate in regular aerobic activities. They may participate in team sports and contact or collision activities provided that they utilize appropriate protective equipment. There seems to be no increased risk of injury or increasing seizure activity as the result of such participation. Persons with seizure disorders still are discouraged from participating in scuba diving and skydiving. The benefits of participation in regular sporting activity far outweigh any risk to the athlete with a seizure disorder who chooses to participate in sports.

Different ketogenesis strategies lead to disparate seizure outcomes.

Science.gov (United States)

Dolce, Alison; Santos, Polan; Chen, Weiran; Hoke, Ahmet; Hartman, Adam L

2018-07-01

Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further. Published by Elsevier B.V.

Non-invasive imaging of epileptic seizures in vivo using photoacoustic tomography

Energy Technology Data Exchange (ETDEWEB)

Zhang Qizhi; Carney, Paul R; Yuan Zhen; Jiang Huabei [J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611 (United States); Liu Zhao [Department of Pediatrics, Division of Pediatric Neurology, University of Florida, Gainesville, FL 32610 (United States); Chen Huanxin; Roper, Steven N [Department of Neurosurgery, University of Florida, Gainesville, FL 32610-0265 (United States)], E-mail: hjiang@bme.ufl.edu

2008-04-07

Non-invasive laser-induced photoacoustic tomography (PAT) is an emerging imaging modality that has the potential to image the dynamic function of the brain due to its unique ability of imaging biological tissues with high optical contrast and ultrasound resolution. Here we report the first application of our finite-element-based PAT for imaging of epileptic seizures in an animal model. In vivo photoacoustic images were obtained in rats with focal seizures induced by microinjection of bicuculline, a GABA{sub A} antagonist, into the neocortex. The seizure focus was accurately localized by PAT as confirmed with gold-standard electroencephalogram (EEG). Compared to the existing neuroimaging modalities, PAT not only has the unprecedented advantage of high spatial and temporal resolution in a single imaging modality, but also is portable and low in cost, making it possible to bring brain imaging to the bedside.

MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset