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Sample records for acid-induced status epilepticus

  1. Status epilepticus

    NARCIS (Netherlands)

    Hensiek, AE; Absalom, Anthony

    2006-01-01

    Status epilepticus is defined as epileptic activity that continues for more than 30 minutes as a single seizure or as recurrent seizures without inter-ictal return of consciousness. The seizure activity is usually classified as partial or generalized. Although status epilepticus is an uncommon admis

  2. Excitatory amino acid transporter 2 downregulation correlates with thalamic neuronal death following kainic acid-induced status epilepticus in rat.

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    Sakurai, Masashi; Kurokawa, Haruna; Shimada, Akinori; Nakamura, Kazuhiro; Miyata, Hajime; Morita, Takehito

    2015-02-01

    Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 weeks after birth, body weight 250-300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1β and iNOS.

  3. Salidroside protects against kainic acid-induced status epilepticus via suppressing oxidative stress.

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    Si, Pei-Pei; Zhen, Jun-Li; Cai, Yun-Lei; Wang, Wen-Jing; Wang, Wei-Ping

    2016-04-01

    There are numerous mechanisms by which the brain generates seizures. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Salidroside (SDS) extracted from Rhodiola rosea L. shows multiple bioactive properties, such as neuroprotection and antioxidant activity in vitro and in vivo. This study explored the role of SDS in kainic acid (KA)-induced SE and investigated the underlying mechanism. Latency to SE increased in the SDS-pretreated mice compared to the KA group, while the percentage of incidence of SE was significantly reduced. These results suggested that pretreatment with SDS not only delayed SE, but it also decreased the incidence of SE induced by KA. KA increased MDA level and reduced the production of SOD and GSH at multiple timepoints after KA administration. SDS inhibited the change of MDA, SOD and GSH induced by KA prior to SE onset, indicating that SDS protects against KA-induced SE via suppressing oxidative stress. Based on these results, we investigated the possible molecular mechanism of SDS. Pretreatment with SDS reversed the KA-induced decrease in AMP-activated protein kinase (AMPK); increased the sirtuin 1 (SIRT1) deacetylase activity in KA-treated mice, which had no demonstrable effect on SIRT1 mRNA and protein; and suppressed the KA-induced increase in Ace-FoxO1. These results showed that AMPK/SIRT1/FoxO1 signaling is possibly the molecular mechanism of neuroprotection by SDS.

  4. Ultrastructural changes to rat hippocampus in pentylenetetrazol- and kainic acid-induced status epilepticus: A study using electron microscopy.

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    Zhvania, Mzia G; Ksovreli, Mariam; Japaridze, Nadezhda J; Lordkipanidze, Tamar G

    2015-07-01

    A pentylenetetrazol (PTZ)-induced status epilepticus model in rats was used in the study. The brains were studied one month after treatment. Ultrastructural observations using electron microscopy performed on the neurons, glial cells, and synapses, in the hippocampal CA1 region of epileptic brains, demonstrated the following major changes over normal control brain tissue. (i) There is ultrastructural alterations in some neurons, glial cells and synapses in the hippocampal CA1 region. (ii) The destruction of cellular organelles and peripheral, partial or even total chromatolysis in some pyramidal cells and in interneurons are observed. Several astrocytes are proliferated or activated. Presynaptic terminals with granular vesicles and degenerated presynaptic profiles are rarely observed. (iii) The alterations observed are found to be dependent on the frequency of seizure activities following the PTZ treatment. It was observed that if seizure episodes are frequent and severe, the ultrastructure of hippocampal area is significantly changed. Interestingly, the ultrastructure of CA1 area is found to be only moderately altered if seizure episodes following the status epilepticus are rare and more superficial; (iv) alterations in mitochondria and dendrites are among the most common ultrastructural changes seen, suggesting cell stress and changes to cellular metabolism. These morphological changes, observed in brain neurons in status epilepticus, are a reflection of epileptic pathophysiology. Further studies at the chemical and molecular level of neurotransmitter release, such as at the level of porosomes (secretory portals) at the presynaptic membrane, will further reveal molecular details of these changes.

  5. Status epilepticus in adults.

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    Betjemann, John P; Lowenstein, Daniel H

    2015-06-01

    Status epilepticus is a common neurological emergency with considerable associated health-care costs, morbidity, and mortality. The definition of status epilepticus as a prolonged seizure or a series of seizures with incomplete return to baseline is under reconsideration in an effort to establish a more practical definition to guide management. Clinical research has focused on early seizure termination in the prehospital setting. The approach of early escalation to anaesthetic agents for refractory generalised convulsive status epilepticus, rather than additional trials of second-line anti-epileptic drugs, to avoid neuronal injury and pharmaco-resistance associated with prolonged seizures is gaining momentum. Status epilepticus is also increasingly identified in the inpatient setting as the use of extended electroencephalography monitoring becomes more commonplace. Substantial further research to enable early identification of status epilepticus and efficacy of anti-epileptic drugs will be important to improve outcomes.

  6. Partial motor status epilepticus

    OpenAIRE

    Gilberto Rebello de Mattos; José C. Rollemberg Filho

    1992-01-01

    We report the case of a young female patient with photosensitive primary epilepsy who presented partial motor status epilepticus provoked by the act of shutting the eyes. Clinical, EEG and neuroimage data are presented and discussed.

  7. STATUS EPILEPTICUS: A REVIEW

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    B. Adibeik

    2009-01-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.Keywords:Status Epilepticus (SE, adults, children, neonates.

  8. Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.

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    Hanna B Laurén

    Full Text Available Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA-induced status epilepticus (SE in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed, and long-term potentiation (LTP; 18 genes changed. Also genes involved in Ca(2+ homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP, apolipoprotein E (apo E, cannabinoid type 1 receptor (CB1, Purkinje cell protein 4 (PEP-19, and interleukin 8 receptor (CXCR1, with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE. However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the

  9. STATUS EPILEPTICUS: A REVIEW

    Directory of Open Access Journals (Sweden)

    B. Adibeik

    2008-10-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.

  10. Convulsive status epilepticus in children

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    Redžek-Mudrinić Tatjana

    2010-01-01

    Full Text Available Introduction. Convulsive status epilepticus is the most urgent neurological medical emergency in children. Generalized convulsive status epilepticus is the most common and life-threatening type of status epilepticus. It is not a syndrome in the same sense as febrile convulsions, benign rolandic epilepsy, and infantile polymorphic epilepsy. These latter disorders have a tight age frame, seizure semiology, and a reasonably predictable outcome. Episodes of convulsive status epilepticus can occur in each: occasionally in symptomatic and febrile convulsions, and Lennox Gastaut syndrome, rarely in benign rolandic epilepsy, and West syndrome. Etiology of convulsive status epilepticus. Status epilepticus has many causes, which vary depending on the age and patient population. Convulsive status epileptucus continues to be associated with significant neurological morbidity and mortality, with different hazards and outcome. Although the outcome is dependent on etiology, it is known that appropriate early management may reduce mortality and some of the morbidity associated with convulsive status epilepticus. Discussion. Status epilepticus is a disorder in which the mechanisms attempting at terminating the seizure fail. Continued convulsive activity in convulsive status epilepticus results in decompensation of all organs and systems, thus being life threatening. Seizure activity in convulsive status epilepticus is associated with neuronal damage. The aim should be to halt this activity urgently, using, ideally, a 100% effective drug, administered quickly, without compromising the consciousness level or producing other negative effects on cardiovascular, respiratory function or other unexpected effects.

  11. Status epilepticus in scleromyxedema

    Institute of Scientific and Technical Information of China (English)

    Soifa Markoula; Soifa Zouroudi; Soitrios Giannopoulos; Kimon Tsoukanelis; Ananstasia Zikou; Athanassios P Kyritsis

    2016-01-01

    Scleromyxedema is a rare dermatologic disorder, characterized by erythematous or yelowish lichenoid waxy papules. Neurological manifestations are rare but wel-recognized. A 51-year-old woman, diagnosed with scleromyxedema, was admitted to the hospital with status epilepticus, caused by brain lesions, as disclosed in a brain magnetic resonance imaging (MRI). The patient was treated with anticonvulsants and corticosteroids and gradualy recovered fuly. A complete remission of the lesions was shown in a folow-up brain MRI. In cases with scleromyxedema and the presence of neurological manifestations, we need to pay attention to central nervous system involvement, especialy when combined with brain MRI lesions, and treat the patient appropriately.

  12. Mitochondrial and nuclear damages and caspase-3 expression in the hippicampal CA3 region of rats with kainic acid induced status epilepticus

    Institute of Scientific and Technical Information of China (English)

    Shuhai Tang; Jianying Sun; Xiaojun Pan; Li Zhang

    2006-01-01

    BACKGROUND: Some scholars believed that the neuronal injury after status epilepticus is apoptosis,the main evidence is the changes of expressions of various apoptosis releted genes,such as immediate-early gene,p53 gene and genes of bcl-2 family,etc.But there is still no ultrastructural evidence for apoptosis.OBJECTIVE: To observe the ultrastructural damages of mitochondrion and nucleus and the changes of caspase expression in neurons of hippocampal CA3 region in rats with status epilepticus induced by kainic acid.DESIGN: A randomized controlled study.SETTING: Department of Anesthesiology and Department of Neurology,Qilu Hospital of Shandong University.MATERIALS: Seventy-five adult male Wistar rats of 250-300 g.clean degree,were provided by the experimental animal center of Shandong University.Kainic acid was purchased from Sigma Company (USA);rabbit anti-rat polyclonal antibody caspase-3 from Santa Cruz Company(USA).METHODS:The experiments were carried out in the Department of Anesthesiology,Qilu Hospital of Shandong University from October 2005 to February 2006.①The 75 rats were randomly divided into experimental group (n=45)and control group(n=30).②Model establishment,convulsion grading and the judging standards for status epilepticus:Rats in the experimental group were given intraperitoneal injection of kainic acid(10 mg/kg),and those in the control group were injected with saline of the same volume.The time of seizure was recorded and their behavioral manifestations were observed,and the seizure was terminated by intraperitoneal injection of diazepam(10 mg/kg).③Observation under electron microscope:At 3, 12 and 24 hours after status epilepticus respectively,bilateral hippocampal tissues were taken out,semithin sections of about 75 nm were prepared after fixation,dehydration and embedding,and then observed under H-800 transmission electron microscope.④Immunohistochemical detection:Bilateral hippocampi were removed at 3,12 and 24 hours after status

  13. Nonconvulsive status epilepticus after electroconvulsive therapy

    DEFF Research Database (Denmark)

    Povlsen, Uffe Juul; Wildschiødtz, Gordon; Høgenhaven, Hans;

    2003-01-01

    SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining...

  14. Management of Status Epilepticus in Children

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    Douglas M. Smith

    2016-04-01

    Full Text Available Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s, as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children.

  15. Therapie des Status epilepticus

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    Trinka E

    2009-01-01

    Full Text Available Der Status epilepticus (SE ist nach dem Schlaganfall der häufigste neurologische Notfall. Er stellt als generaliserter konvulsiver SE (GKSE die schwerste Ausprägung eines epileptischen Anfalls dar, der mit einer signifikanten Morbidität und einer ca. 20%igen Letalität verbunden ist. Nur bei der Hälfte der Patienten mit SE besteht zuvor eine Epilepsie; die meisten Fälle sind symptomatisch, wobei Schädel- Hirn-Traumata, zerebrovaskuläre Erkrankungen, ZNS-Infektionen und metabolische Ursachen führend sind. Bei Patienten mit vorbestehender Epilepsie lässt sich eine frühe Phase des GKSE erkennen, in der die Anfälle crescendoartig zunehmen, bis sie in kontinuierliche Anfallsaktivität münden (etablierte Phase. Das Management eines GKSE verlangt rasches und beherztes Vorgehen. Neben der sofort einzuleitenden Therapie muss gleichzeitig die artdiagnostische Zuordnung des SE und die Ursache erkannt und behandelt werden. Als Therapie der ersten Wahl sind Benzodiazepine etabliert, wobei intravenösem (i.v. Lorazepam gegenüber Diazepam der Vorzug zu geben ist. Versagt die Therapie mit Benzodiazepinen, muss rasch und konsequent nach einem Stufenschema vorgegangen werden. Phenytoin/Fosphenytoin, Valproinsäure, Levetiracetam und Lacosamid sind als i.v. Formulierung erhältliche Antiepileptika. Obwohl Vergleichsstudien hier fehlen, wird Phenytoin bevorzugt. Valproat und Levetiracetam sind nicht sedierend und kardiovaskulär gut verträglich, sodass hier Alternativen zu Phenytoin vorhanden sind. Lacosamid ist eine neue Therapieoption, deren Stellenwert erst bestimmt werden muss. Versagt auch die zweite Therapiestufe, so muss der Patient intubiert und in Allgemeinanästhesie intensivmedizinisch behandelt werden. Dafür stehen Thiopental, Propofol oder hoch dosiertes Midazolam zu Verfügung. Durch den eklatanten Mangel an randomisierten Studien bleibt die Therapie des GKSE empirisch und durch den Off-label-Einsatz gekennzeichnet.

  16. Changes and overlapping distribution in the expression of CB1/OX1-GPCRs in rat hippocampus by kainic acid-induced status epilepticus.

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    Zhu, Fei; Wang, Xiang-Qing; Chen, Ya-Nan; Yang, Nan; Lang, Sen-Yang; Zuo, Ping-Ping; Zhang, Jia-Tang; Li, Rui-Sheng

    2015-02-01

    Status epilepticus (SE) is a life-threatening neurological disorder. It is important to discover new drugs to control SE without the development of pharmacoresistance. Focus on the cannabinoid receptor and cannabinoid-related compounds might be a good option. Cannabinoid receptor 1 (CB1) and orexin receptor 1 (OX1) both belong to the GPCR superfamily and display "cross-talk" interactions, however, there has been no study of the effect of OX1/CB1 in epilepsy. Therefore, we investigated the potential long-term effects of SE on CB1 and OX1 expression in rat hippocampus, aiming to elucidate whether they are involved in the causative mechanism of epilepsy and whether they might form a heterodimer. In this study, SE was induced with kainic acid, and results of immunohistochemistry and RT-PCR both showed that the expression of CB1 in the hippocampus increased after SE and was significantly higher compared to controls especially 1 week post-SE. However we did not find any significant difference in the expression of OX1 between the SE group and the controls at any time. Under immunofluorescence staining, we observed an overlapping distribution of CB1 and OX1 in the hippocampus. The increased expression of CB1 in the hippocampus indicates that CB1 may play an important role in the underlying mechanism of SE, but the effect of OX1 was not obvious. The overlapping distribution of CB1 and OX1 in the hippocampus indicates that they may form a heterodimer to exert their effect in epilepsy.

  17. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

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    Lin Ching-Huei

    2011-05-01

    Full Text Available Abstract Background Kainic acid (KA-induced status epilepticus (SE was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Methods Rodents (male FVB mice and Sprague-Dawley rats were fed with sesamin extract (90% of sesamin and 10% sesamolin, 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA, neurodegeneration (Caspase-3, and inflammation (COX-2 in PC12 cells and microglial BV-2 cells. Results Treatment with sesamin extract (30 mg/kg significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA from 145% to 117% (p = 0.017 and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p = 0.013. The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. Conclusions Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

  18. [Treatment of non-convulsive status epilepticus].

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    Liimatainen, Suvi; Ollikainen, Jyrki; Peltola, Jukka

    2011-01-01

    Non-convulsive status epilepticus is an insidious condition and a challenging diagnosis for neurologists on call. The condition must, however, be recognized, since it constitutes a neurological emergency. Non-convulsive status epilepticus may also be associated as an additional complication with an acute neurologic disease, in which case an EEG recording is usually required. In addition, non-convulsive status epilepticus can be found in a significant proportion of patients with unconsciousness of unknown origin. PMID:21995129

  19. Drug-induced status epilepticus.

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    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  20. Nonconvulsive status epilepticus disguising as hepatic encephalopathy.

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    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-04-28

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.

  1. Current Trends in Treatment of Status Epilepticus and Refractory Status Epilepticus.

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    Betjemann, John P

    2015-12-01

    Status epilepticus is a heterogeneous disorder with varied definitions and presentations. Taken together, all forms of status epilepticus carry significant morbidity and mortality, much of which is dictated by the underlying etiology. Generalized convulsive status epilepticus, which represents a common form, is a true neurologic emergency that requires emergent management. Treatment focuses on stabilizing the patient and aggressive medical management to achieve the timely termination of seizures. For other forms of status epilepticus including nonconvulsive and focal status epilepticus, the goal remains early seizure termination, but the use of intravenous medications should be weighed against the risks associated with these therapies. The diagnostic evaluation of status epilepticus is guided by the patient's history and should be broad, including a screen for toxins, electrolytes, structural abnormalities, and central nervous system infectious and autoimmune/inflammatory etiologies. Considerable research is still needed to improve our understanding of the mechanisms, consequences, and therapy of status epilepticus.

  2. Genetic mutations associated with status epilepticus.

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    Bhatnagar, M; Shorvon, S

    2015-08-01

    This paper reports the results of a preliminary search of the literature aimed at identifying the genetic mutations reported to be strongly associated with status epilepticus. Genetic mutations were selected for inclusion if status epilepticus was specifically mentioned as a consequence of the mutation in standard genetic databases or in a case report or review article. Mutations in 122 genes were identified. The genetic mutations identified were found in only rare conditions (sometimes vanishingly rare) and mostly in infants and young children with multiple other handicaps. Most of the genetic mutations can be subdivided into those associated with cortical dysplasias, inborn errors of metabolism, mitochondrial disease, or epileptic encephalopathies and childhood syndromes. There are no identified 'pure status epilepticus genes'. The range of genes underpinning status epilepticus differs in many ways from the range of genes underpinning epilepsy, which suggests that the processes underpinning status epilepticus differ from those underpinning epilepsy. It has been frequently postulated that status epilepticus is the result of a failure of 'seizure termination mechanisms', but the wide variety of genes affecting very diverse biochemical pathways identified in this survey makes any unitary cause unlikely. The genetic influences in status epilepticus are likely to involve a wide range of mechanisms, some related to development, some to cerebral energy production, some to diverse altered biochemical pathways, some to transmitter and membrane function, and some to defects in networks or systems. The fact that many of the identified genes are involved with cerebral development suggests that status epilepticus might often be a system or network phenomenon. To date, there are very few genes identified which are associated with adult-onset status epilepticus (except in those with preexisting neurological damage), and this is disappointing as the cause of many adult

  3. Genetic mutations associated with status epilepticus.

    Science.gov (United States)

    Bhatnagar, M; Shorvon, S

    2015-08-01

    This paper reports the results of a preliminary search of the literature aimed at identifying the genetic mutations reported to be strongly associated with status epilepticus. Genetic mutations were selected for inclusion if status epilepticus was specifically mentioned as a consequence of the mutation in standard genetic databases or in a case report or review article. Mutations in 122 genes were identified. The genetic mutations identified were found in only rare conditions (sometimes vanishingly rare) and mostly in infants and young children with multiple other handicaps. Most of the genetic mutations can be subdivided into those associated with cortical dysplasias, inborn errors of metabolism, mitochondrial disease, or epileptic encephalopathies and childhood syndromes. There are no identified 'pure status epilepticus genes'. The range of genes underpinning status epilepticus differs in many ways from the range of genes underpinning epilepsy, which suggests that the processes underpinning status epilepticus differ from those underpinning epilepsy. It has been frequently postulated that status epilepticus is the result of a failure of 'seizure termination mechanisms', but the wide variety of genes affecting very diverse biochemical pathways identified in this survey makes any unitary cause unlikely. The genetic influences in status epilepticus are likely to involve a wide range of mechanisms, some related to development, some to cerebral energy production, some to diverse altered biochemical pathways, some to transmitter and membrane function, and some to defects in networks or systems. The fact that many of the identified genes are involved with cerebral development suggests that status epilepticus might often be a system or network phenomenon. To date, there are very few genes identified which are associated with adult-onset status epilepticus (except in those with preexisting neurological damage), and this is disappointing as the cause of many adult

  4. Nonconvulsive status epilepticus disguising as hepatic encephalopathy

    OpenAIRE

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-01-01

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconv...

  5. Prognostic Factors for Refractory Status Epilepticus

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    J. Gordon Millichap

    2013-03-01

    Full Text Available Researchers at the Mayo Clinic, Rochester, MN studied the outcome and identified prognostic factors for refractory status epilepticus (RSE in 54 adult patients, median age 52 years [range 18-93].

  6. Epidemiology of Status Epilepticus in Children

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    J Gordon Millichap

    2007-09-01

    Full Text Available The incidence, etiology, seizure characteristics, and outcome in childhood convulsive status epilepticus (CSE are reviewed by researchers from Great Ormond Street Hospital for Children, and the Institute of Child Health, London, UK.

  7. Nonconvulsive status epilepticus after electroconvulsive therapy

    DEFF Research Database (Denmark)

    Povlsen, Uffe Juul; Wildschiødtz, Gordon; Høgenhaven, Hans;

    2003-01-01

    SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining the...... diagnosis on the basis of the clinical manifestations. The application of electroencephalography is recommended in monitoring patients with prolonged confusion following ECT. Concurrent drug therapy and ECT is discussed....

  8. Aborted and refractory status epilepticus in children : A comparative analysis

    NARCIS (Netherlands)

    Lambrechtsen, Florise A. C. P.; Buchhalter, Jeffrey R.

    2008-01-01

    Purpose: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), an

  9. Early Developmental Outcome Following Convulsive Status Epilepticus

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    J Gordon Millichap

    2013-08-01

    Full Text Available Investigators at the Developmental Cognitive Neurosciences Unit, Institute of Child Health, London, other centers in the UK, and Dartmouth School of Medicine, NH, USA, prospectively recruited children aged between 1 and 42 months from North London who had at least one episode of convulsive status epilepticus (CSE and classified them as prolonged febrile seizures (PFS or nonfebrile CSE.

  10. Risk of Status Epilepticus in Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-10-01

    Full Text Available The occurrence of status epilepticus (SE after the initial diagnosis of epilepsy was determined in a prospective community-based cohort study of 613 children at Montefiore Medical Center, Bronx, NY; Yale Medical School, New Haven, CT; and BIOS/NIU, DeKalb, IL.

  11. Acute polyhydramnios after maternal status epilepticus

    OpenAIRE

    Shindo, Ryosuke; Aoki, Shigeru; Kasai, Michi; Takahashi, Tsuneo; Hirahara, Fumiki

    2015-01-01

    Key Clinical Message Maternal status epilepticus can cause fetal hypoxic ischemic encephalopathy that in turn results in acute polyhydramnios caused by fetal dysphagia; thus, acute polyhydramnios is a symptom that should lead to a suspicion of fetal dysphagia caused by hypoxic ischemic encephalopathy.

  12. Mild hypothermia for refractory focal status epilepticus in an infant with hemimegalencephaly

    NARCIS (Netherlands)

    Elting, Jan Willem; van der Naalt, Joukje; Fock, Johanna Maria

    2010-01-01

    Hypothermia can reduce seizure frequency in animal models of status epilepticus, and its effectiveness in human status epilepticus has been reported occasionally. We report an infant with hemimegalencephaly who presented with generalized status epilepticus. After high dose intravenous drug therapy,

  13. Management of super refractory status epilepticus with isoflurane and hypothermia

    Directory of Open Access Journals (Sweden)

    Charles Patrick Gilman

    2015-01-01

    Full Text Available Super-refractory status epilepticus is status epilepticus that continues beyond 24 hours and includes those cases in which epilepsy is recurrent upon reduction or withdrawal of treatment. We describe the presentation and successful management of a male patient with super-refractory status epilepticus using the inhaled anesthetic, isoflurane, and mild hypothermia (HT. The potential utility of combined HT and volatile anesthesia is discussed.

  14. Management of super refractory status epilepticus with isoflurane and hypothermia

    OpenAIRE

    Charles Patrick Gilman

    2015-01-01

    Super-refractory status epilepticus is status epilepticus that continues beyond 24 hours and includes those cases in which epilepsy is recurrent upon reduction or withdrawal of treatment. We describe the presentation and successful management of a male patient with super-refractory status epilepticus using the inhaled anesthetic, isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed.

  15. Status epilepticus associated with borage oil ingestion.

    Science.gov (United States)

    Al-Khamees, Wafa'a A; Schwartz, Michael D; Alrashdi, Saleh; Algren, Adam D; Morgan, Brent W

    2011-06-01

    The use of herbal and complementary medicine is common. Many herbal products are known to produce serious adverse effects. Borage oil is derived from the seeds of the borage plant (Borago officinalis) an abundant source of gamma-linolenic acid (GLA), and Borage oil has been promoted as a treatment for rheumatoid arthritis, atopic dermatitis, diabetic neuropathy, and menopause-related symptoms. We report a case of status epilepticus in a patient who consumed borage oil for one week. PMID:21387119

  16. Status epilepticus: Analysis of refractory cases

    OpenAIRE

    B. P. Gladov; O. A. Podgornaya; P. N. Vlasov

    2016-01-01

    Objective: to analyze refractory status epilepticus (SE) cases.Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs), such as diazepam (DZP); valproic acid (VPA); levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE thera...

  17. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    Science.gov (United States)

    Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S.

    2015-01-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children. PMID:25363147

  18. Status Epilepticus in Adults: A Review of Diagnosis and Treatment.

    Science.gov (United States)

    Lawson, Thomas; Yeager, Susan

    2016-04-01

    Status epilepticus is a medical emergency that requires rapid diagnosis and treatment. Nonconvulsive status epilepticus is frequently underdiagnosed and therefore undertreated, which can lead to permanent neuronal damage resulting in disability or death. Despite the frequent occurrence and morbidity associated with status epilepticus, this topic has received little attention within the literature. A systematic approach to treatment should start with management of airway, breathing, and circulation, followed by administration of benzodiazepines and intravenous antiepileptic drugs, and rapid escalation of therapy to prevent morbidity and mortality. Armed with the information in this article, nurses will have a higher-level understanding of what to do when encountering a patient in status epilepticus. PMID:27037340

  19. Brain tumour-associated status epilepticus.

    Science.gov (United States)

    Goonawardena, Janindu; Marshman, Laurence A G; Drummond, Katharine J

    2015-01-01

    We have reviewed the scant literature on status epilepticus in patients with brain tumours. Patients with brain tumour-associated epilepsy (TAE) appear less likely to develop status epilepticus (TASE) than patients with epilepsy in the general population (EGP) are to develop status epilepticus (SEGP). TASE is associated with lesions in similar locations as TAE; in particular, the frontal lobes. However, in contrast to TAE, where seizures commence early in the course of the disease or at presentation, TASE is more likely to occur later in the disease course and herald tumour progression. In marked contrast to TAE, where epilepsy risk is inversely proportional to Word Health Organization tumour grade, TASE risk appears to be directly proportional to tumour grade (high grade gliomas appear singularly predisposed). Whilst anti-epileptic drug (AED) resistance is more common in TAE than EGP (with resistance directly proportional to tumour grade and frontal location), TASE appears paradoxically more responsive to simple AED regimes than either TAE or SEGP. Although some results suggest that mortality may be higher with TASE than with SEGP, it is likely that (as with SEGP) the major determinant of mortality is the underlying disease process. Because all such data have been derived from retrospective studies, because TASE and SEGP are less common than TAE and EGP, and because TASE and SEGP classification has often been inconsistent, findings can only be considered preliminary: multi-centre, prospective studies are required. Whilst preliminary, our review suggests that TASE has a distinct clinical profile compared to TAE and SEGP.

  20. Can anesthetic treatment worsen outcome in status epilepticus?

    Science.gov (United States)

    Sutter, Raoul; Kaplan, Peter W

    2015-08-01

    Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus".

  1. Pyridoxine deficiency in adult patients with status epilepticus.

    Science.gov (United States)

    Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan

    2015-11-01

    An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels.

  2. Cerebrospinal fluid tau proteins in status epilepticus.

    Science.gov (United States)

    Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo F; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa

    2015-08-01

    Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus".

  3. Electrographic status epilepticus in children with critical illness: Epidemiology and outcome.

    Science.gov (United States)

    Abend, Nicholas S

    2015-08-01

    Electrographic seizures and electrographic status epilepticus are common in children with critical illness with acute encephalopathy, leading to increasing use of continuous EEG monitoring. Many children with electrographic status epilepticus have no associated clinical signs, so EEG monitoring is required for seizure identification. Further, there is increasing evidence that high seizure burdens, often classified as electrographic status epilepticus, are associated with worse outcomes. This review discusses the incidence of electrographic status epilepticus, risk factors for electrographic status epilepticus, and associations between electrographic status epilepticus and outcomes, and it summarizes recent guidelines and consensus statements addressing EEG monitoring in children with critical illness. This article is part of a Special Issue entitled "Status Epilepticus".

  4. Nonconvulsive Status Epilepticus in Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Hyung Kim

    2011-05-01

    Full Text Available We discuss a case of a 64-year-old male with a history of liver failure presenting with altered mental status, initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus (NCSE by electroencephalogram (EEG. NCSE is a difficult diagnosis to make, given no clear consensus on diagnostic criteria. Especially in the intensive care unit setting of persistent altered mental status with no clear etiology, NCSE must be considered in the differential diagnosis, as the consequences of delayed diagnosis and treatment can be substantial. EEG can be useful in the evaluation of patients with hepatic encephalopathy who have persistently altered levels of consciousness despite optimal medical management. [West J Emerg Med. 2011;12(4:372–374.

  5. New lessons: Classic treatments in convulsive status epilepticus.

    LENUS (Irish Health Repository)

    Renganathan, R

    2012-02-03

    Convulsive status epilepticus is a relatively common life-threatening illness requiring prompt intervention. There has been much debate about the appropriate protocol for management of convulsive status epilepticus. Published data on the management of this condition in Ireland is limited. Our aim was to establish if there was a structured, evidence-based or consensus-based protocol being implemented in the management of status epilepticus in our centre. We retrospectively audited all charts with a diagnosis of \\'Status Epilepticus\\' admitted to our hospital from January 1998 to December 2002. A total of 95 episodes of convulsive status epilepticus were recorded. 34 charts were reviewed. Benzodiazepines were the drug class of first choice in 96% of patients. However, the doses of benzodiazepines used varied widely. The most frequent dose of phenytoin used was 1 gram. No one received continuous EEG monitoring during treatment of refractory status epilepticus. Overall mortality was 18%. The results of this study show that there is no consistent protocol was being followed for the management of convulsive status epilepticus in our centre. The drugs of first choice varied between diazepam and lorazepam in most cases. Although phenytoin was used as second line drug, the dose used was frequently suboptimal. We have developed a protocol for the management for convulsive status in our centre.

  6. Prallethrin Poisoning Presenting as Status Epilepticus

    Directory of Open Access Journals (Sweden)

    D Vijayaraju

    2014-02-01

    Full Text Available Mosquito repellents contain pyrethroid derivatives, as the active ingredient. Data regarding human toxicity following oral intake is limited. This is a case report of an individual who presented with neurotoxicity following oral ingestion of prallethrin (2.4% w/w of a higher concentration present in formulations commercially available than previously. A 22 year old male presented to the emergency Room (ER in status epilepticus. He was managed in the Intensive Care Unit (ICU. No cause for his status could be determined after all laboratory investigations. A review of history with the patient revealed that he had ingested a bottle of liquid mosquito repellent (45 ml. The patient has had no further symptoms on follow up and has been off anti epileptics. Pyrethroid containing mosquito repellents act on neuronal sodium channels causing hyperexcitiability. With no known specific antidotes, symptomatic treatment is the main stay of management.

  7. Non-convulsive status epilepticus in the elderly.

    Science.gov (United States)

    Cheng, Shuli

    2014-12-01

    Altered mental state is a very common presentation in the elderly admitted to the emergency department. It has been determined that about 16% of patients aged 60 or older with confusion of unknown origin have non-convulsive status epilepticus. The diagnosis of non-convulsive status epilepticus is difficult in the elderly because possible aetiologies of confusion may present with the same clinical picture. Non-convulsive status epilepticus in the elderly carries major morbidity and mortality, attributable primarily to aetiology, and treatment is complex, involving treatment of the aetiology and concomitant medical illnesses, whilst balancing the side effects and drug interactions of antiepileptic drugs.

  8. Status Epilepticus: Epidemiology and Public Health Needs

    Science.gov (United States)

    Sánchez, Sebastián; Rincon, Fred

    2016-01-01

    Status epilepticus (SE) is defined as a continuous clinical and/or electrographic seizure activity lasting five minutes or more or recurrent seizure activity without return to baseline. There is a paucity of epidemiological studies of SE, as most research is derived from small population studies. The overall incidence of SE is 9.9 to 41 per 100,000/year, with peaks in children and the elderly and with febrile seizures and strokes as its main etiologies. The etiology is the major determinant of mortality. Governments and the academic community should predominantly focus on the primary prevention of etiologies linked to SE, as these are the most important risk factors for its development. This review describes the incidence, prevalence, etiology, risk factors, outcomes and costs of SE and aims to identify future research and public health needs. PMID:27537921

  9. Primary Amoebic (Naegleria fowleri Meningoencephalitis Presenting as Status Epilepticus

    Directory of Open Access Journals (Sweden)

    A Sharma

    2011-04-01

    Full Text Available Primary amebic meningoencephalitis (PAM is a rare entity. Usual presenting features are fever, headache and seizures with meningeal signs and this disease carries high mortality rate. We present a case report of PAM presenting as status epilepticus.

  10. Autoimmunity and inflammation in status epilepticus: from concepts to therapies.

    Science.gov (United States)

    Holzer, Franz Josef; Seeck, Margitta; Korff, Christian M

    2014-10-01

    The understanding of immunological mechanisms underlying some forms of epilepsy and encephalitis has rapidly increased for the last 10 years leading to the concept of status epilepticus of autoimmune origin. Actual treatment recommendations regarding autoimmune status epilepticus are based on retrospective case studies, pathophysiological considerations and experts' opinion. In addition, there are no clear indicators to predict outcome. In situations where autoimmune mechanisms are suspected in patients with status epilepticus, there is evidence that earlier treatment is related to better outcome. Increased awareness is mandatory to decrease the number of patients with major neurological problems or fatal outcome, which is overall about 50%. We here summarize findings of all pediatric and adult patients reported to date, and review the current state of knowledge in the field of immune therapeutic approaches of status epilepticus.

  11. Ketogenic diet in 3 cases of childhood refractory status epilepticus

    DEFF Research Database (Denmark)

    Sort, Rune; Born, Alfred P; Pedersen, Karen N.;

    2013-01-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus ...... in several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution....

  12. Neuroactive steroids for the treatment of status epilepticus.

    Science.gov (United States)

    Rogawski, Michael A; Loya, Carlos M; Reddy, Kiran; Zolkowska, Dorota; Lossin, Christoph

    2013-09-01

    Benzodiazepines are the current first-line standard-of-care treatment for status epilepticus but fail to terminate seizures in about one third of cases. Synaptic GABAA receptors, which mediate phasic inhibition in central circuits, are the molecular target of benzodiazepines. As status epilepticus progresses, these receptors are internalized and become functionally inactivated, conferring benzodiazepine resistance, which is believed to be a major cause of treatment failure. GABAA receptor positive allosteric modulator neuroactive steroids, such as allopregnanolone, also potentiate synaptic GABAA receptors, but in addition they enhance extrasynaptic GABAA receptors that mediate tonic inhibition. Extrasynaptic GABAA receptors are not internalized, and desensitization of these receptors does not occur during continuous seizures in status epilepticus models. Here we review the broad-spectrum antiseizure activity of allopregnanolone in animal seizure models and the evidence for its activity in models of status epilepticus. We also demonstrate that allopregnanolone inhibits ongoing behavioral and electrographic seizures in a model of status epilepticus, even when there is benzodiazepine resistance. Parenteral allopregnanolone may provide an improved treatment for refractory status epilepticus.

  13. The nature of neonatal status epilepticus--a clinician's perspective.

    Science.gov (United States)

    Dlugos, Dennis J

    2015-08-01

    Neonatal status epilepticus occurs within the substrate of the hyperexcitable newborn brain and is usually provoked by acute CNS derangements, although status can also be the presentation of early-life epilepsy. Provoked neonatal status usually resolves within a few days, with or without treatment, but new data suggests that status is associated with adverse outcomes, even after controlling for underlying disease severity and MRI structural brain injury. Novel treatments may be needed to improve seizure control and outcome, given the characteristics of neurotransmission in the newborn brain. This article is part of a Special Issue entitled "Status Epilepticus".

  14. Underestimated Rate of Status Epilepticus according to the Traditional Definition of Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Cheung-Ter Ong

    2015-01-01

    Full Text Available Purpose. Status epilepticus (SE is an important neurological emergency. Early diagnosis could improve outcomes. Traditionally, SE is defined as seizures lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness. Some specialists argued that the duration of seizures qualifying as SE should be shorter and the operational definition of SE was suggested. It is unclear whether physicians follow the operational definition. The objective of this study was to investigate whether the incidence of SE was underestimated and to investigate the underestimate rate. Methods. This retrospective study evaluates the difference in diagnosis of SE between operational definition and traditional definition of status epilepticus. Between July 1, 2012, and June 30, 2014, patients discharged with ICD-9 codes for epilepsy (345.X in Chia-Yi Christian Hospital were included in the study. A seizure lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness were considered SE according to the traditional definition of SE (TDSE. A seizure lasting between 5 and 30 min was considered SE according to the operational definition of SE (ODSE; it was defined as underestimated status epilepticus (UESE. Results. During a 2-year period, there were 256 episodes of seizures requiring hospital admission. Among the 256 episodes, 99 episodes lasted longer than 5 min, out of which 61 (61.6% episodes persisted over 30 min (TDSE and 38 (38.4% episodes continued between 5 and 30 min (UESE. In the 38 episodes of seizure lasting 5 to 30 minutes, only one episode was previously discharged as SE (ICD-9-CM 345.3. Conclusion. We underestimated 37.4% of SE. Continuing education regarding the diagnosis and treatment of epilepsy is important for physicians.

  15. Status epilepticus: Analysis of refractory cases

    Directory of Open Access Journals (Sweden)

    B. P. Gladov

    2016-01-01

    Full Text Available Objective: to analyze refractory status epilepticus (SE cases.Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs, such as diazepam (DZP; valproic acid (VPA; levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE therapy complications noted only in the intravenous administration of narcotics (propofol, sodium thiopental.Results and discussion. A fetal outcome due to multiple organ dysfunction indirectly related to SE was recorded in 2 (13.3% patients with acute symptomatic status. SE was abolished in the other 13 cases. The preliminary findings may suggest that it is appropriate to prescribe VPA just at the prehospital stage. The co-administration of VPA and DZP substantially enhances the efficiency of SE therapy. The maximum acceptable doses of AEDs using the whole available therapeutic arsenal should be administered within the first hours of acute symptomatic SE.

  16. Status epilepticus: Why, what, and how

    Directory of Open Access Journals (Sweden)

    P P Nair

    2011-01-01

    Full Text Available Status epilepticus (SE is an important neurological emergency with high mortality and morbidity. The first official definition of SE was the product of 10 th Marseilles colloquium held in 1962 which was accepted by International League Against Epilepsy in 1964. There are as many types of SE as of seizures. SE is supposed to result from failure of normal mechanisms that terminate an isolated seizure. In half of the cases, there is no history of epilepsy and SE is precipitated by some intercurrent infection. In children, it is often infection, whereas in adults, the major causes are stroke, hypoxia, metabolic derangements, and alcohol intoxication or drug withdrawal. The treatment of SE aims at termination of SE, prevention of seizure recurrence, management of precipitating causes, and the management of complications. The extent of investigations done should be based on the clinical picture and cost benefit analysis. The first line antiepileptic drugs (AED for SE include benzodiazepines, phenytoin, phosphenytoin, and sodium valproate. Mortality of SE ranges between 7 and 39% and depends on underlying cause and response to AEDs.

  17. 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.

  18. Status epilepticus in the elderly: differential diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Mauricio EA

    2011-03-01

    Full Text Available Elizabeth Ann Mauricio, William David FreemanMayo Clinic, Jacksonville, FL, USADate of Preparation 28th January 2011 Conflict of interest: None declaredAbstract: Seizures are not an uncommon occurrence in older adults, and the incidence of status epilepticus is much greater in the elderly than in younger populations. Status epilepticus is a neurologic emergency and requires prompt intervention to minimize morbidity and mortality. Treatment involves both supportive care as well as initiation of medications to stop all clinical and electrographic seizure activity. Benzodiazepines are used as first-line agents, followed by antiepileptic drugs when seizures persist. In refractory status epilepticus, urgent neurologic consultation is indicated for the titration of anesthetic agents to a level of appropriate background suppression on EEG. In light of our aging population, physician awareness and competence in the management of status epilepticus is imperative and should be recognized as a growing public health concern.Keywords: status epilepticus, convulsive, generalized, nonconvulsive, refractory, elderly, treatment 

  19. Surgical treatment of status epilepticus: a palliative approach.

    Science.gov (United States)

    Winkler, Peter A

    2013-09-01

    Although status epilepticus (SE) does not resemble a domain for neurosurgical indications in single occasions, a microneurosurgical procedure in patients with catastrophic epilepsy and status epilepticus should be considered as an ultimate ratio-choice in these patients. From a personal series of >600 epilepsy surgery procedures in a period from August 1, 1993 until March 13, 2013, 22 patients were identified with catastrophic epilepsy and all of them with at least one episode of status epilepticus. Five of the patients had surgery under ongoing status epilepticus. Twelve patients became seizure-free, two patients had >90% seizure reduction, seven patients >50% seizure reduction, and one patient was unchanged. No surgery-related complications in terms of permanent morbidity were ascertained in the presented series. In the subgroup of the five patients operated in the acute phase of SE one patient became seizure-free (Engel class. I), one showed Engel class II, two Engel class III, and one Engel class IV with no worthwhile improvement. Patients with catastrophic epilepsy including status epilepticus can benefit from resective epilepsy surgery, even with incomplete resection of the epileptogenic lesion.

  20. On Etiology and Mortality Rate of Status Epilepticus

    OpenAIRE

    F Ashraf Zadeh

    2000-01-01

    The etiology and mortality rate of Status Epilepticus in 60 pediatric patients, aged 2 months to 13 years, during 10 years has been evaluated. The results show that: -41.7% of the patients were female and 58.3% male. -65% of patients were<3 years and 35% >3 years old. - Mortality rate was 21.6%, 46.1% of which were referral patients. -Major causes of Status Epilepticus were: Idiopathic epilepsy 33%, prolonged febrile seizure 17%, electrolyte imbalance 13%, meningitis 10%, sepsis 8%, enc...

  1. How to Manage Electrical Status Epilepticus in Sleep.

    Science.gov (United States)

    Veggiotti, Pierangelo; Pera, Maria Carmela; Olivotto, Sara; De Giorgis, Valentina

    2016-02-01

    Electrical status epilepticus in sleep is an age-dependent syndrome with the characteristic pattern of continuous spike and waves during non-rapid eye movement sleep. Most children can present developmental deterioration. The demonstration of the EEG pattern has to rely on all night long EEG recordings. A comprehensive neuropsychologic evaluation with periodic reassessment should be performed. For the idiopathic forms of electrical status epilepticus in sleep, clobazam could be considered as the first-line therapy; in the other cases, corticosteroids, in particular intravenous methylprednisolone pulse therapy, remain the most effective and should be considered the therapy of choice.

  2. Partial status epilepticus - rapid genetic diagnosis of Alpers' disease.

    LENUS (Irish Health Repository)

    McCoy, Bláthnaid

    2011-11-01

    We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers\\' disease should be considered in any child presenting with partial status epilepticus.

  3. Complete recovery after severe myxoedema coma complicated by status epilepticus

    DEFF Research Database (Denmark)

    Fjølner, Jesper; Opstrup, Ulla Kampmann; Søndergaard, Esben;

    2015-01-01

    We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly...

  4. New experimental therapies for status epilepticus in preclinical development.

    Science.gov (United States)

    Walker, Matthew C; Williams, Robin S B

    2015-08-01

    Starting with the established antiepileptic drug, valproic acid, we have taken a novel approach to develop new antiseizure drugs that may be effective in status epilepticus. We first identified that valproic acid has a potent effect on a biochemical pathway, the phosphoinositide pathway, in Dictyostelium discoideum, and we demonstrated that this may relate to its mechanism of action against seizures in mammalian systems. Through screening in this pathway, we have identified a large array of fatty acids and fatty acid derivatives with antiseizure potential. These were then evaluated in an in vitro mammalian system. One compound that we identified through this process is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids that are mediating the antiseizure effect of this diet. We further tested two of the more potent compounds in an in vivo model of status epilepticus and demonstrated that they were more effective than valproic acid in treating the status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

  5. Consequences of Inappropriate ER Management of Status Epilepticus

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-11-01

    Full Text Available The clinical features of status epilepticus (SE requiring admission to pediatric intensive care (PTC and the emergency pre-PIC treatment of SE compared to standard guidelines were studied in relation to the course of SE after admission to PIC at Great Ormond Street Hospital for Children, London, UK.

  6. Supra-recommendation Treatment of Super-refractory Status Epilepticus

    Science.gov (United States)

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-01-01

    A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India. PMID:27390680

  7. Systemic complications of status epilepticus--An update.

    Science.gov (United States)

    Hocker, Sara

    2015-08-01

    Systemic complications occur at every stage of status epilepticus, involve every organ system, and may worsen outcome. Initially, there is a massive catecholamine release and hyperadrenergic state that may result in neurocardiogenic, pulmonary, and, sometimes, musculoskeletal or renal injury. Further medical complications accompany the various treatments used to abort the seizures including the use of nonanesthetic antiseizure drugs and high-dose anesthetic infusions. Later, sequelae of prolonged immobility and critical illness occur and add to the cumulative morbidity of these patients. Clinicians should follow a protocol to guide screening for early markers of systemic injury, complications of specific pharmacologic and adjunctive treatments, and periodic surveillance for complications related to prolonged immobility. This article is part of a Special Issue entitled "Status Epilepticus".

  8. Outcomes in pediatric patients with nonconvulsive status epilepticus.

    Science.gov (United States)

    Jafarpour, Saba; Loddenkemper, Tobias

    2015-08-01

    Recognition of nonconvulsive status epilepticus (NCSE) is gaining increasing attention in the assessment and evaluation of critically ill pediatric patients. The underlying cause of NCSE is often the most important factor in determining outcome. However, there is a growing body of literature suggesting that electrical seizure burden in NCSE also contributes to unfavorable outcomes. Determination of impact of NCSE on outcome based on current evidence involves consideration of heterogeneous study settings, study populations, and process of care and outcome measures. In addition, the lack of data on neurocognitive function prior to episodes of NCSE as well as limited long-term neurocognitive assessment data confines precise conclusions about neurocognitive changes. This article is part of a Special Issue entitled "Status Epilepticus".

  9. Supra-recommendation Treatment of Super-refractory Status Epilepticus

    OpenAIRE

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-01-01

    A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She req...

  10. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    OpenAIRE

    Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S

    2014-01-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnano...

  11. Cefepime- Induced Non-Convulsive Status Epilepticus (NCSE)

    OpenAIRE

    Kim, Ahro; KIM, Ji-Eun; Paek, Young-Min; Hong, Keun-Sik; Cho, Young-Jin; Cho, Joong-Yang; Park, Hee-Kyung; Koo, Hyeon-Kyoung; Song, Pamela

    2013-01-01

    Cefepime is a fourth-generation B-lactam cephalosporin, commonly used in immunosuppressed patients. Neurotoxicity, which present as nonconvulsive status epilepticus (NCSE), has been reported previously especially in adult patients with impaired renal function. We present a case of cefepime induced NCSE after recovering from acute renal failure. A 71-year-old woman was hospitalized for right lower lobe lobectomy after diagnosis of lung cancer. Although she had successful lobectomy, she underwe...

  12. Nonconvulsive status epilepticus secondary to paclitaxel administration ☆

    OpenAIRE

    Ignacio Illán-Gala; Francisco Javier Díaz de Terán; Pablo Alonso; María-José Aguilar-Amat

    2015-01-01

    Nonconvulsive status epilepticus (NCSE) can be triggered by metabolic disturbances and drugs in adults without previous epilepsy. We present the case of a 51-year-old woman without previous history of epilepsy and recently diagnosed with infiltrating lobular breast carcinoma. Following the administration of paclitaxel–cremophor, she presented a striking disinhibited behavior with episodic spatial disorientation, emotional indifference, and irritability. Urgent EEG was consistent with NCSE. Cl...

  13. Neurogenic pulmonary edema in a child with status epilepticus

    OpenAIRE

    Bindu T Nair; Sajith Surendran; Dinesh Yadav

    2016-01-01

    Neurogenic pulmonary edema (NPE) is defined as acute pulmonary edema after a sudden neurologic insult. It develops after a significant central nervous system insult such as trauma, hemorrhage or seizures and can occur both in adults and children. A 6-year-old male child, known case of cerebral palsy was brought to the emergency department in status epilepticus. He had severe respiratory distress with pink frothy secretions pouring from the mouth. Clinical and radiological examination was sugg...

  14. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    OpenAIRE

    A. Moayedi; A. Atashabparvar; E.Eftekhari

    2008-01-01

    ObjectiveThis study was designed to determine the etiology of status epilepticus (SE) andits relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, ...

  15. Impact of the erythropoietin-derived peptide mimetic Epotris on the histopathological consequences of status epilepticus

    DEFF Research Database (Denmark)

    Zellinger, Christina; Seeger, Natalie; Hadamitzky, Martin;

    2011-01-01

    of this peptide to interfere with the histopathological consequences of electrical-induced status epilepticus in rats. The peptide attenuated status epilepticus-associated expansion of the neuronal progenitor cell population in a significant manner. Moreover, Epotris affected the number of persistent basal...

  16. Predictors of Outcome of Convulsive Status Epilepticus Among an Egyptian Pediatric Tertiary Hospital.

    Science.gov (United States)

    Halawa, Eman F; Draz, Iman; Ahmed, Dalia; Shaheen, Hala A

    2015-11-01

    Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality.

  17. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    Directory of Open Access Journals (Sweden)

    A. Moayedi

    2008-11-01

    Full Text Available ObjectiveThis study was designed to determine the etiology of status epilepticus (SE andits relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, and mortality. We classified the etiology according to international league against epilepsy (ILAE classification and also uses another classification regarding underlying causes such as fever (non-CNS infection, central nervous system infection, hypoxia, and metabolic causes.ResultsStatus epilepticus was responsible for 0.3% of all hospital  dmissions during the study period. Based on the ILAE classification, frequencies for acute symptomatic, febrile, progressive encephalopathic, remote, and cryptogenic SE were 42.5%, 32.5%, 10%, 7.5%, and 7.5%, respectively.The most common underlying causes resulting in SE were fever (45%, metabolic disorders (15%, CNS infection (12.5%, chronic neurologic diseases (7.5%, idiopathic (7.5%, hypoxia (5%, drug withdrawal (2.5%, CNS hemorrhage (2.5%, neurodegenerative disease (2.5%, brain abscess (2.5%, and post DPT (Diphteria,Pertusis,Tetanus vaccination (2.5%. Mortality rate was 25% (80% in the patients younger than 5 years and 40% in those aged less than 1 year. Occurrence of SE and its mortality was found to be related to age (pConclusionFor SE, if seizures continue for more than 5 minutes, treatment must beinitiated. The outcome is determined by etiology, age, seizure duration and management; however, all we can do is enhance the management and increase its effectiveness.Keywords:Status epilepticus, Etiology, Underlying cause

  18. Algorithm for the treatment of status epilepticus: an Australian perspective.

    Science.gov (United States)

    Jones, C L; Koios, J

    2016-04-01

    Convulsive status epilepticus (SE) is a medical emergency where successful treatment is associated with timely intervention and the use of a protocol has been recommended to provide the highest quality of care. Despite this, there is no nationally available protocol for the treatment of SE in adults in Australia. Treatment is therefore variable and often based on international guidelines or familiarity with certain medications. We have developed an Australian-based algorithm for the treatment of SE, focusing on simplifying management while delivering the safest possible care. We believe this algorithm is suitable for all health practitioners, regardless of training or experience. PMID:27062207

  19. Neurogenic pulmonary edema in a child with status epilepticus

    Directory of Open Access Journals (Sweden)

    Bindu T Nair

    2016-01-01

    Full Text Available Neurogenic pulmonary edema (NPE is defined as acute pulmonary edema after a sudden neurologic insult. It develops after a significant central nervous system insult such as trauma, hemorrhage or seizures and can occur both in adults and children. A 6-year-old male child, known case of cerebral palsy was brought to the emergency department in status epilepticus. He had severe respiratory distress with pink frothy secretions pouring from the mouth. Clinical and radiological examination was suggestive of NPE. Child was immediately ventilated and all supportive measures were started. Child showed marked improvement within 48 h of admission with diuresis and positive end-expiratory pressure (PEEP assisted ventilation.

  20. Status epilepticus: Using antioxidant agents as alternative therapies

    Science.gov (United States)

    Carmona-Aparicio, Liliana; Zavala-Tecuapetla, Cecilia; González-Trujano, María Eva; Sampieri, Aristides Iii; Montesinos-Correa, Hortencia; Granados-Rojas, Leticia; Floriano-Sánchez, Esaú; Coballase-Urrutía, Elvia; Cárdenas-Rodríguez, Noemí

    2016-01-01

    The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state.

  1. Refractory generalised convulsive status epilepticus : a guide to treatment.

    Science.gov (United States)

    Kälviäinen, Reetta; Eriksson, Kai; Parviainen, Ilkka

    2005-01-01

    The patient with status epilepticus has continuous or rapidly repeating seizures. Generalised convulsive status epilepticus (GCSE) is the most common form of the disorder and is a life-threatening condition that requires prompt medical management. Status epilepticus that does not respond to first-line benzodiazepines (lorazepam or diazepam) or to second-line antiepileptic drugs (phenytoin/fosphenytoin, phenobarbital or valproate) is usually considered refractory and requires more aggressive treatment. The optimal treatment of refractory GCSE has not been defined, but patients should be treated in an intensive care unit, as artificial ventilation and haemodynamic support are required. Invasive haemodynamic monitoring is often necessary and EEG monitoring is essential. The drug treatment of refractory GCSE involves general anaesthesia with continuous intravenous anaesthetics given in doses that abolish all clinical and electrographic epileptic activity, often requiring sedation to the point of burst suppression on the EEG. Barbiturate anaesthetics, pentobarbital in the US and thiopental sodium in Europe and Australia, are the most frequently used agents and are highly effective for refractory GCSE both in children and adults. Indeed, they remain the only way to stop seizure activity with certainty in severely refractory cases. Other options are midazolam for adults and children and propofol for adults only.Regardless of the drug selected, intravenous fluids and vasopressors are usually required to treat hypotension. Once seizures have been controlled for 12-24 hours, continuous intravenous therapy should be gradually tapered off if the drug being administered is midazolam or propofol. Gradual tapering is probably not necessary with pentobarbital or thiopental sodium. Continuous EEG monitoring is required during high-dose treatment and while therapy is gradually withdrawn. During withdrawal of anaesthetic therapy, intravenous phenytoin/fosphenytoin or valproate should

  2. Status epilepticus: Using antioxidant agents as alternative therapies

    Science.gov (United States)

    Carmona-Aparicio, Liliana; Zavala-Tecuapetla, Cecilia; González-Trujano, María Eva; Sampieri, Aristides Iii; Montesinos-Correa, Hortencia; Granados-Rojas, Leticia; Floriano-Sánchez, Esaú; Coballase-Urrutía, Elvia; Cárdenas-Rodríguez, Noemí

    2016-01-01

    The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state. PMID:27698680

  3. Refractory status epilepticus following self-poisoning with the organochlorine pesticide endosulfan.

    Science.gov (United States)

    Roberts, Darren M; Dissanayake, Wasantha; Rezvi Sheriff, M H; Eddleston, Michael

    2004-09-01

    We describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with the organochlorine insecticide endosulfan. Although rarely seen in developed countries, pesticide poisoning particularly with endosulfan is an important cause of difficult-to-manage seizures in Asian countries. In this case report, we discuss the management of status epilepticus and refractory status epilepticus. Further, we specifically discuss the clinical pharmacology and toxicology of endosulfan. PMID:15337143

  4. Generalized status epilepticus associated with massive pulmonary aspiration and transient central diabetes insipidus: case report

    Directory of Open Access Journals (Sweden)

    CARVALHO MAURICIO

    2000-01-01

    Full Text Available Status epilepticus causes significant morbidity and mortality. A case of generalized status epilepticus followed by massive pulmonary aspiration, acute respiratory failure and transient central diabetes insipidus is presented. Seizures were promptly controlled, but the patient required mechanical ventilation and correction of polyuria with desmopressin acetate. During hospitalization mental status improved, diabetes insipidus spontaneously remitted and he was discharged without neurologic sequelae. The clinical and pathophysiological features of this case are discussed.

  5. Ketogenic diet for adults in super-refractory status epilepticus

    Science.gov (United States)

    Thakur, Kiran T.; Probasco, John C.; Hocker, Sara E.; Roehl, Kelly; Henry, Bobbie; Kossoff, Eric H.; Kaplan, Peter W.; Geocadin, Romergryko G.; Hartman, Adam L.; Venkatesan, Arun

    2014-01-01

    Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE. PMID:24453083

  6. Guidelines for the evaluation and management of status epilepticus.

    Science.gov (United States)

    Brophy, Gretchen M; Bell, Rodney; Claassen, Jan; Alldredge, Brian; Bleck, Thomas P; Glauser, Tracy; Laroche, Suzette M; Riviello, James J; Shutter, Lori; Sperling, Michael R; Treiman, David M; Vespa, Paul M

    2012-08-01

    Status epilepticus (SE) treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. To provide guidance for the acute treatment of SE in critically ill patients, the Neurocritical Care Society organized a writing committee to evaluate the literature and develop an evidence-based and expert consensus practice guideline. Literature searches were conducted using PubMed and studies meeting the criteria established by the writing committee were evaluated. Recommendations were developed based on the literature using standardized assessment methods from the American Heart Association and Grading of Recommendations Assessment, Development, and Evaluation systems, as well as expert opinion when sufficient data were lacking.

  7. Cortico-thalamic activation in generalized status epilepticus, a PET study

    NARCIS (Netherlands)

    de Jong, B. M.; van de Hoeven, J. H.; Pruim, J.; van der Naalt, J.; Meertens, John H. J. M.

    2008-01-01

    In a patient with a refractory generalized convulsive status epilepticus, the ictal distribution of regional cerebral glucose was assessed with positron emission tomography (PET). Synchronized seizure activity in the EEG was associated with bilateral metabolic activation of medial sensorimotor regio

  8. Serial CT scans of cerebral hypoxia due to prolonged status epilepticus

    Energy Technology Data Exchange (ETDEWEB)

    Saiwai, Shigeo; Matsumura, Yasumasa; Tamaoka, Koichi; Fukuda, Teruo; Miyamoto, Takeshi (Kobe Central Municipal Hospital, Kobe (Japan))

    1983-04-01

    Serial computed tomography (CT) scans of 5 infants with status epilepticus were reviewed. Four out of the 5 infants fortunately had CT scans before status epilepticus because of a convulsion. There was a diffuse and mild low density in the hemisphere, with small ventricles and tight sulci (brain swelling) at 1 to 2 days after ictus. Thereafter, a diffuse low density became apparent except for the cerebellum, the brain stem, the thalamus, and the basal ganglia. Two to 4 weeks after ictus, a localized, mottled low density was demonstrated on the cerebral mantle and atrophic changes became progressively clear. In 3 cases, no abnormal enhancement was elicited on contrast CT scans performed between 5 to 16 days after status epilepticus. We discussed the possible pathophysiological aspects of the brain damage due to ''prolonged status epilepticus.''

  9. Encephalopathy with status epilepticus during sleep (ESES) induced by oxcarbazepine in idiopathic focal epilepsy in childhood

    DEFF Research Database (Denmark)

    Pavlidis, Elena; Rubboli, Guido; Nikanorova, Marina;

    2015-01-01

    Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin...

  10. Which EEG patterns in coma are nonconvulsive status epilepticus?

    Science.gov (United States)

    Trinka, Eugen; Leitinger, Markus

    2015-08-01

    Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma. Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary. The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future. This article is part of a Special Issue entitled "Status Epilepticus".

  11. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    Directory of Open Access Journals (Sweden)

    A. Moayedi

    2007-11-01

    Full Text Available ObjectiveThis study was designed to determine the etiology of status epilepticus (SE and its relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, and mortality. We classified the etiology according to international league against epilepsy (ILAE classification and also uses another classification regarding underlying causes such as fever (non-CNS infection, central nervous system infection, hypoxia, and metabolic causes.Results Status epilepticus was responsible for 0.3% of all hospital admissions during the study period. Based on the ILAE classification, frequencies for acute symptomatic, febrile, progressive encephalopathic, remote, and cryptogenic SE were 42.5%, 32.5%, 10%, 7.5%, and 7.5%, respectively.The most common underlying causes resulting in SE were fever (45%, metabolic disorders (15%, CNS infection (12.5%, chronic neurologic diseases (7.5%, idiopathic (7.5%, hypoxia (5%, drug withdrawal (2.5%, CNS hemorrhage (2.5%, neurodegenerative disease (2.5%, brain abscess (2.5%, and post DPT(Diphteria,Pertusis,Tetanus vaccination (2.5%. Mortality rate was 25% (80% in the patients younger than 5 years and 40% in those aged less than 1 year. Occurrence of SE and its mortality was found to be related to age (p< 0.05.ConclusionFor SE, if seizures continue for more than 5 minutes, treatment must be initiated. The outcome is determined by etiology, age, seizure duration and management; however, all we can do is enhance the management and increase its effectiveness.

  12. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    Science.gov (United States)

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed. PMID:25674075

  13. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    OpenAIRE

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed.

  14. P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus.

    Science.gov (United States)

    Henshall, David C; Engel, Tobias

    2015-08-01

    There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

  15. Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus.

    Science.gov (United States)

    Duffy, B A; Chun, K P; Ma, D; Lythgoe, M F; Scott, R C

    2014-03-01

    Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10mg/kg or 2mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2mg/kg and 10mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus.

  16. Status epilepticus as the only presentation of the neonatal Bartter syndrome

    Directory of Open Access Journals (Sweden)

    Soumya Patra

    2012-01-01

    Full Text Available Bartter syndrome is a rare hereditary (autosomal recessive salt-losing tubulopathy characterized by hypokalemia, hypochloremia, metabolic alkalosis, and normal blood pressure with hyperreninemia, The underlying renal abnormality results in excessive urinary losses of sodium, chloride, and potassium. We report a case of a four-month-old infant with neonatal Bartter syndrome, who presented only with status epilepticus. To the best of our present knowledge, there is no reported case of Bartter syndrome who presented with status epilepticus.

  17. Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats

    Institute of Scientific and Technical Information of China (English)

    Zhaoliang Liang; Fei Gao; Fajun Wang; Xiaochen Wang; Xinyu Song; Kejing Liu; Ren-Zhi Zhan

    2013-01-01

    Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer.

  18. Modified Atkins diet for the treatment of nonconvulsive status epilepticus in children.

    Science.gov (United States)

    Kumada, Tomohiro; Miyajima, Tomoko; Kimura, Nobusuke; Saito, Keiko; Shimomura, Hideki; Oda, Nozomi; Fujii, Tatsuya

    2010-04-01

    The authors describe the use of a modified Atkins diet for the treatment of 2 children with nonconvulsive status epilepticus. Patient 1 was a 4-year-and-11-month-old girl diagnosed with frontal lobe epilepsy. Since the age of 3 years and 10 months, she had daily nonconvulsive status epilepticus resistant to antiepileptic agents. Patient 2 was a 5-year-and-5-month-old girl with subcortical band heterotopia. She had nonconvulsive status epilepticus daily since the age of 5 years. They were treated with the modified Atkins diet, in which carbohydrate intake was restricted to 10 g/d without restriction on protein, caloric, or fluid intake. The nonconvulsive status epilepticus disappeared 5 and 10 days after the initiation of the diet treatment, respectively. They have been on the diet treatment and free from nonconvulsive status epilepticus for 19 and 4 months, respectively. The modified Atkins diet appears to be very effective for the treatment of nonconvulsive status epilepticus.

  19. Hippocampal sclerosis and status epilepticus: cause or consequence? A MRI study; Esclerose hipocampal e status epilepticus: causa ou consequencia? Um estudo de RM

    Energy Technology Data Exchange (ETDEWEB)

    Kuster, Gustavo Wruck; Braga-Neto, Pedro; Santos-Neto, Denizart; Santana, Maria Teresa Garcia; Barsottini, Orlando Graziani [Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo, SP (Brazil). Dept. of Neurology. Div. of General Neurology]. E-mail: gwkuster@hotmail.com; Maia Junior, Antonio Carlos Martins [Fleury Institute, Sao Paulo, SP (Brazil). Magnetic Resonance Imaging Unit

    2007-12-15

    Background: Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in status epilepticus. These abnormalities can be followed by hippocampal sclerosis. Case Report: We report a 15-year-old lady with focal non convulsive status epilepticus (NCSE) and focal slowing on EEG. DWI exhibited abnormal hyperintense signals in bilateral temporal and insular cortices. After 3 weeks, MRI performed a localized hippocampal atrophy. Conclusion: The MRI findings indicated vasogenic and cytotoxic edema during seizure activity and subsequent loss of brain parenchyma. (author)

  20. Etiology and prognosis of non-convulsive status epilepticus.

    Science.gov (United States)

    Kang, Bong Su; Jhang, Yunsook; Kim, Young-Soo; Moon, Jangsup; Shin, Jung-Won; Moon, Hye Jin; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Park, Kyung-Il; Lee, Sang Kun

    2014-11-01

    Although non-convulsive status epilepticus (NCSE) is an important type of epilepsy, it is not often recognized. In order to analyze the clinical characteristics and outcome in patients with NCSE, we examined the medical records of patients with NCSE admitted to the Seoul National University Hospital between June 2005 and October 2008. The clinical details and electroencephalography records of 34 adult NCSE patients (aged over 16 years) were collected. Their mean age was 47 years (standard deviation 20 years, range, 16-87 years), and 20 were female. Twenty-seven patients (79.4%) showed decreased awareness with acute onset, and seven (20.6%) were obtunded or comatose. Ten patients (29.4%) had a history of epilepsy, and four (11.8%) had a history of stroke. NCSE was etiologically attributed to acute medical or neurological problems in 25 patients (73.5%), was cryptogenic in three (8.8%), and was secondary to underlying epilepsy in six (17.7%). Acute symptomatic etiology was associated with poor recovery (p=0.048), with all unresponsive patients in this acute symptomatic group. Eight (23.5%) of the 34 NCSE patients did not recover or died, whereas nine (26.5%) recovered. Our study shows that the presence of acute symptoms or central nervous system infection is associated with poor outcome, suggesting that a high level of vigilance is required to identify and prevent complications.

  1. Local cerebral glucose utilization during status epilepticus in newborn primates

    Energy Technology Data Exchange (ETDEWEB)

    Fujikawa, D.G.; Dwyer, B.E.; Lake, R.R.; Wasterlain, C.G.

    1989-06-01

    The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-(/sup 14/C)-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc in frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.

  2. Acetazolamide for electrical status epilepticus in slow-wave sleep.

    Science.gov (United States)

    Fine, Anthony L; Wirrell, Elaine C; Wong-Kisiel, Lily C; Nickels, Katherine C

    2015-09-01

    Electrical status epilepticus in slow-wave sleep (ESES) is characterized by nearly continuous spike-wave discharges during non-rapid eye movement (REM) sleep. ESES is present in Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWS). Sulthiame has demonstrated reduction in spike-wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre- and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers. PMID:26230617

  3. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

    Science.gov (United States)

    Trinka, Eugen; Cock, Hannah; Hesdorffer, Dale; Rossetti, Andrea O; Scheffer, Ingrid E; Shinnar, Shlomo; Shorvon, Simon; Lowenstein, Daniel H

    2015-10-01

    The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor

  4. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

    Science.gov (United States)

    Trinka, Eugen; Cock, Hannah; Hesdorffer, Dale; Rossetti, Andrea O; Scheffer, Ingrid E; Shinnar, Shlomo; Shorvon, Simon; Lowenstein, Daniel H

    2015-10-01

    The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor

  5. Efficacy of Continuous High Dose Midazolam Infusion in Childhood Refractory Generalized Convulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Afshin Fayyazi

    2011-06-01

    Full Text Available bjeciveProlonged and uncontrolled refractory status epilepticus (SE is a life-threatening medical emergency in children (1,2,3. There is no consensus on the optimal therapy for refractory status epilepticus (1. The aim of this study was to develop a new method for treating patients with refractory status epilepticus.Materials & MethodsTen children with refractory status epilepticus in Mofid Hospital, who did not respond to 10 μg/kg per min of intravenous midazolam, had their dose of midazolam increased to 30 μg/kg per min. All children were monitored for the development of side effects.ResultsTen children with no response to low-dose midazolam were given a higher dose of midazolam, and 5 (50% children had a good response. These patients had significantly different response to high-dose midazolam.One patient in the high-dose midazolam group was intubated and required mechanical ventilation. The duration of stay in the hospital and PICU and on mechanical ventilation in patients with no response to low-dose midazolam following with other drugs was longer than in the high-dose midazolam group.No death occurred in high dose midazolam group.ConclusionHigh-midazolam dose drip infusion is a safe and effective protocol for refractory status epilepticus in children.

  6. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    Science.gov (United States)

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.

  7. Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

    Science.gov (United States)

    Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

    2016-05-01

    Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols. PMID:26518205

  8. Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

    Science.gov (United States)

    Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

    2016-05-01

    Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols.

  9. MIDAZOLAM EFFICACY AND SIDE EFFECTS IN GENERALIZED AND PARTIAL REFRACTORY STATUS EPILEPTICUS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    M.R. Salehi Omran

    2009-04-01

    Full Text Available ObjectiveMidazolam is a significant and effective drug for control of a life-threatening condition, generalized and partial refractory convulsive status epilepticus. The goal of this study was evaluation of midazolam efficacy for management of this serious disease and its two side effects, hypotension and respiratory failure.Materials & MethodsOur study was done using a quasi experimental method; 22 children with generalized refractory convulsive status epilepticus and 13 with partial refractory convulsive status epilepticus were enrolled for the study. All patients received 0.2mg/kg/dose as a bolus intravenous midazolam followed by 1-6 mcg/kg/min continuous intravenous midazolam. Following this, termination of seizures as well as hypotension and respiratory failure were evaluated.ResultsMidazolam ceased stop convulsions in 81.81% (18 patients with generalized seizures, and in 76.92% (10 patients with partial seizures, showing no significant difference between these two types of seizures (p=0.52 Hypotension was induced in 18.18% (4 patients with generalized seizures and in 30.70% (4 patients with partial seizures, again difference not significant (p=0.14. There was respiratory failure in 21.73% (5 patients with generalized seizure and in 7.69% (1 patients with partial seizure, difference not significant.(p=0.09ConclusionThere was no significant difference in efficacy and creation of hypotension and respiratory failure after continuous intravenous infusion of midazolam between generalized and partial refractory convulsive status epilepticus.Key words:Midazolam, Refractory convulsive status epilepticus, Convulsive status epilepticus.

  10. Febrile infection-related status epilepticus in a child after a common infection

    DEFF Research Database (Denmark)

    Andersen, Anne Helene; Hansen, Lars Kjærsgaard

    2014-01-01

    A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology.......A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology....

  11. Changes on diffusion-weighted MRI with focal motor status epilepticus: case report

    Energy Technology Data Exchange (ETDEWEB)

    Loevblad, K.O. [Neuroradiology, Radiodiagnostic, Hopital Cantonal de Geneve HUG, Geneve (Switzerland); Senn, P.; Zutter, D.; Bassetti, C.; Donati, F. [Dept. of Neurology, Inselspital, Univ. Hospital, Berne (Switzerland); Loevblad, K.O.; Zeller, O.; Schroth, G. [Div. of Neuroradiology, Inselspital, Univ. Hospital, Berne (Switzerland)

    2003-04-01

    Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in focal status epilepticus. The changes on DWI provide an insight into the pathophysiology. We report a 53-year-old man with focal motor status epilepticus involving the left hand, arm and face with focal slowing on EEG. The apparent diffusion coefficients (ADC) were higher in the affected hemisphere than on the other side. At 10 days and 6 weeks after the end of the seizures, we saw normal ADCs and atrophy of the affected hemisphere. We conclude that the MRI findings indicate both cytotoxic and vasogenic oedema during seizure activity and subsequent loss of brain parenchyma. (orig.)

  12. Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus.

    Science.gov (United States)

    Jimenez-Mateos, Eva M; Engel, Tobias; Merino-Serrais, Paula; Fernaud-Espinosa, Isabel; Rodriguez-Alvarez, Natalia; Reynolds, James; Reschke, Cristina R; Conroy, Ronan M; McKiernan, Ross C; deFelipe, Javier; Henshall, David C

    2015-07-01

    Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects.

  13. Age-dependent changes in intrinsic neuronal excitability in subiculum after status epilepticus.

    Directory of Open Access Journals (Sweden)

    Sungkwon Chung

    Full Text Available Kainic acid-induced status epilepticus (KA-SE in mature rats results in the development of spontaneous recurrent seizures and a pattern of cell death resembling hippocampal sclerosis in patients with temporal lobe epilepsy. In contrast, KA-SE in young animals before postnatal day (P 18 is less likely to cause cell death or epilepsy. To investigate whether changes in neuronal excitability occur in the subiculum after KA-SE, we examined the age-dependent effects of SE on the bursting neurons of subiculum, the major output region of the hippocampus. Patch-clamp recordings were used to monitor bursting in pyramidal neurons in the subiculum of rat hippocampal slices. Neurons were studied either one or 2-3 weeks following injection of KA or saline (control in immature (P15 or more mature (P30 rats, which differ in their sensitivity to KA as well as the long-term sequelae of the KA-SE. A significantly greater proportion of subicular pyramidal neurons from P15 rats were strong-bursting neurons and showed increased frequency-dependent bursting compared to P30 animals. Frequency-dependent burst firing was enhanced in P30, but not in P15 rats following KA-SE. The enhancement of bursting induced by KA-SE in more mature rats suggests that the frequency-dependent limitation of repetitive burst firing, which normally occurs in the subiculum, is compromised following SE. These changes could facilitate the initiation of spontaneous recurrent seizures or their spread from the hippocampus to other parts of the brain.

  14. Treatment of convulsive status epilepticus in the UMCG: A retrospective, observational study

    NARCIS (Netherlands)

    Vlaskamp, D.R.M.; Brouwer, O.F.; Callenbach, P.M.C.

    2013-01-01

    Objectives: Little is known about clinical practice with respect to the application of guidelines in the treatment of Convulsive Status Epilepticus (CSE). This retrospective, observational study evaluated treatment of episodes of CSE in children at the University Medical Centre Groningen (UMCG). Mat

  15. Ten patients with refractory status epilepticus in an intensive care department

    NARCIS (Netherlands)

    ter Maaten, JC; van Schijndel, RJM; Heimans, JJ; Schreuder, WO

    1998-01-01

    Status epilepticus (SE) is a serious disease, associated with a high morbidity and mortality, particularly if refractory to initial therapy. We describe the clinical manifestations and outcome in ten cases with refractory SE admitted to our medical intensive care unit. Three of these selected group

  16. Progranulin promotes activation of microglia/macrophage after pilocarpine-induced status epilepticus.

    Science.gov (United States)

    Zhu, Shanshan; Tai, Chao; Petkau, Terri L; Zhang, Si; Liao, Chengyong; Dong, Zhifang; Wen, Wendy; Chang, Qing; Tian Wang, Yu; MacVicar, Brian A; Leavitt, Blair R; Jia, William; Cynader, Max S

    2013-09-12

    Progranulin (PGRN) haploinsufficiency accounts for up to 10% of frontotemporal lobe dementia. PGRN has also been implicated in neuroinflammation in acute and chronic neurological disorders. Here we report that both protein and mRNA levels of cortical and hippocampal PGRN are significantly enhanced following pilocarpine-induced status epilepticus. We also identify intense PGRN immunoreactivity that colocalizes with CD11b in seizure-induced animals, suggesting that PGRN elevation occurs primarily in activated microglia and macrophages. To test the role of PGRN in activation of microglia/macrophages, we apply recombinant PGRN protein directly into the hippocampal formation, and observe no change in the number of CD11b(+) microglia/macrophages in the dentate gyrus. However, with pilocarpine-induced status epilepticus, PGRN application significantly increases the number of CD11b(+) microglia/macrophages in the dentate gyrus, without affecting the extent of hilar cell death. In addition, the number of CD11b(+) microglia/macrophages induced by status epilepticus is not significantly different between PGRN knockout mice and wildtype. Our findings suggest that status epilepticus induces PGRN expression, and that PGRN potentiates but is not required for seizure-induced microglia/macrophage activation.

  17. Preliminary results of the global audit of treatment of refractory status epilepticus.

    Science.gov (United States)

    Ferlisi, M; Hocker, S; Grade, M; Trinka, E; Shorvon, S

    2015-08-01

    The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus".

  18. Landau-Kleffner Syndrome, Electrical Status Epilepticus in Slow Wave Sleep, and Language Regression in Children

    Science.gov (United States)

    McVicar, Kathryn A.; Shinnar, Shlomo

    2004-01-01

    The Landau-Kleffner syndrome (LKS) and electrical status epilepticus in slow wave sleep (ESES) are rare childhood-onset epileptic encephalopathies in which loss of language skills occurs in the context of an epileptiform EEG activated in sleep. Although in LKS the loss of function is limited to language, in ESES there is a wider spectrum of…

  19. Recovery from near drowning and postanoxic status epilepticus with controlled hypothermia

    NARCIS (Netherlands)

    de Pont, A C J M; de Jager, C P C; van den Bergh, W M; Schultz, M J

    2011-01-01

    A diver was resuscitated after cardiac arrest due to near drowning and was hypothermic on hospital arrival. During rewarming, status epilepticus occurred, previously identified as a predictor of poor outcome. The seizures responded well to treatment with antiepileptic drugs and controlled hypothermi

  20. Reversible changes in echo planar perfusion- and diffusion-weighted MRI in status epilepticus

    Energy Technology Data Exchange (ETDEWEB)

    Flacke, S.; Keller, E.; Urbach, H. [Dept. of Radiology, Univ. of Bonn (Germany); Wuellner, U.; Hamzei, F. [Dept. of Neurology, Univ. of Bonn (Germany)

    2000-02-01

    Perfusion imaging (PI) demonstrated increased perfusion and diffusion-weighted imaging (DWI) showed high signal limited to the left temporoparietal cortex in a 68-year-old man with nonconvulsive status epilepticus. The EEG showed a slow delta-wave focus. The patient recovered and PI, DWI and EEG changes completely resolved. (orig.)

  1. Phase-locking of epileptic spikes to ongoing delta oscillations in non-convulsive status epilepticus

    NARCIS (Netherlands)

    Hindriks, Rikkert; Meijer, Hil G.E.; Gils, van Stephan A.; Putten, van Michel J.A.M

    2013-01-01

    The EEG of patients in non-convulsive status epilepticus (NCSE) often displays delta oscillations or generalized spike-wave discharges. In some patients, these delta oscillations coexist with intermittent epileptic spikes. In this study we verify the prediction of a computational model of the thalam

  2. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms

    NARCIS (Netherlands)

    E.A. van Vliet; W.M. Otte; W.J. Wadman; E. Aronica; G. Kooij; H.E. de Vries; R.M. Dijkhuizen; J.A. Gorter

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  3. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II : Potential mechanisms

    NARCIS (Netherlands)

    van Vliet, Erwin A; Otte, Wim M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  4. Treatment of electrical status epilepticus in sleep : A pooled analysis of 575 cases

    NARCIS (Netherlands)

    Van Den Munckhof, Bart; Van Dee, Violet; Sagi, Liora; Caraballo, Roberto H.; Veggiotti, Pierangelo; Liukkonen, Elina; Loddenkemper, Tobias; Sánchez Fernández, Iván; Buzatu, Marga; Bulteau, Christine; Braun, Kees P J; Jansen, Floor E.

    2015-01-01

    Objective Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Treatment of ESES is assumed to improve cognitive outcome. The aim of this study is to crea

  5. Use of the EpiNet database for observational study of status epilepticus in Auckland, New Zealand.

    Science.gov (United States)

    Bergin, Peter; Jayabal, Jayaganth; Walker, Elizabeth; Davis, Suzanne; Jones, Peter; Dalziel, Stuart; Yates, Kim; Thornton, Vanessa; Bennett, Patricia; Wilson, Kaisa; Roberts, Lynair; Litchfield, Rhonda; Te Ao, Braden; Parmer, Priya; Feigin, Valery; Jost, Jeremy; Beghi, Ettore; Rossetti, Andrea O

    2015-08-01

    The EpiNet project has been established to facilitate investigator-initiated clinical research in epilepsy, to undertake epidemiological studies, and to simultaneously improve the care of patients who have records created within the EpiNet database. The EpiNet database has recently been adapted to collect detailed information regarding status epilepticus. An incidence study is now underway in Auckland, New Zealand in which the incidence of status epilepticus in the greater Auckland area (population: 1.5 million) will be calculated. The form that has been developed for this study can be used in the future to collect information for randomized controlled trials in status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

  6. Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Michele Juliane Vieira

    2014-09-01

    Full Text Available OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus.

  7. Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

    Directory of Open Access Journals (Sweden)

    Kunii Yasuto

    2011-09-01

    Full Text Available Abstract Introduction Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus. Case presentation Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus. Conclusions In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.

  8. Refractory nonconvulsive status epilepticus in coma: analysis of the evolution of ictal patterns

    Directory of Open Access Journals (Sweden)

    Paulo Breno Noronha Liberalesso

    2012-07-01

    Full Text Available OBJECTIVE: Nonconvulsive status epilepticus (NCSE is currently considered as one of the most frequent types of status epilepticus (SE. The objective of the present study was to identify the natural history of the electrographical evolution of refractory NCSE and to establish the relationship between ictal patterns and prognosis. METHODS: We analyzed, retrospectively, 14 patients with loss of consciousness and NCSE. The ictal patterns were classified as discrete seizures (DS, merging seizures (MS, continuous ictal discharges (CID, continuous ictal discharges with flat periods (CID-F, and periodic lateralized epileptiform discharges (PLEDs. RESULTS: The ictal patterns were DS (n=7; 50.0%, PLEDs (n=3; 1.4%, CID (n=2; 14.3%, MS (n=1; 7.1%, and CID-F (n=1; 7.1%. CONCLUSIONS: NCSE electrographic findings are heterogeneous and do not follow a stereotyped sequence. PLEDs were related to a higher probability of neurological morbidity and mortality.

  9. Study on Refractory Status Epilepticus%难治性癫(癎)持续状态

    Institute of Scientific and Technical Information of China (English)

    蒋莉

    2006-01-01

    @@ 由于小儿大脑发育不成熟,对异常刺激的分析、鉴别和抑制能力较弱,易出现癫(癎)样发作,甚至导致癫(癎)持续状态(status epilepticus,SE)和难治性癫(癎)持续状态(refractory status epilepticus).难治性SE是临床危重症,死亡率高,存活者也可因长时程发作产生脑损伤而遗留严重后遗症.以下就难治性SE的一些问题进行简要介绍.

  10. Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency.

    Science.gov (United States)

    Prasanth, Sudhakaran; Shaji, Velayudhan Cheruvallil; Lyla, Chacko; Jayalakshmi, Vasudevapanicker

    2016-01-01

    Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency. PMID:27606021

  11. Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency

    Directory of Open Access Journals (Sweden)

    Sudhakaran Prasanth

    2016-01-01

    Full Text Available Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency.

  12. Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency

    Science.gov (United States)

    Prasanth, Sudhakaran; Shaji, Velayudhan Cheruvallil; Lyla, Chacko; Jayalakshmi, Vasudevapanicker

    2016-01-01

    Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency.

  13. A one-year prospective study of refractory status epilepticus in Modena, Italy.

    Science.gov (United States)

    Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo F; Meletti, Stefano

    2015-08-01

    Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus".

  14. MIDAZOLAM EFFICACY AND SIDE EFFECTS IN GENERALIZED AND PARTIAL REFRACTORY STATUS EPILEPTICUS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    M.R. Salehi Omran

    2009-01-01

    Full Text Available ObjectiveMidazolam is a significant and effective drug for control of a life-threatening condition, generalized and partial refractory convulsive status epilepticus. The goal of this study was evaluation of midazolam efficacy for management of this serious disease and its two side effects, hypotension and respiratory failure.Materials & MethodsOur study was done using a quasi experimental method; 22 children with generalized refractory convulsive status epilepticus and 13 with partial refractory convulsive status epilepticus were enrolled for the study. All patients received 0.2mg/kg/dose as a bolus intravenous midazolam followed by 1-6 mcg/kg/min continuous intravenous midazolam. Following this, termination of seizures as well as hypotension and respiratory failure were evaluated.ResultsMidazolam ceased stop convulsions in 81.81% (18 patients with generalized seizures, and in 76.92% (10 patients with partial seizures, showing no significant difference between these two types of seizures (p=0.52 Hypotension was induced in 18.18% (4 patients with generalized seizures and in 30.70% (4 patients with partial seizures, again difference not significant (p=0.14. There was respiratory failure in 21.73% (5 patients with generalized seizure and in 7.69% (1 patients with partial seizure, difference not significant.(p=0.09ConclusionThere was no significant difference in efficacy and creation of hypotension and respiratory failure after continuous intravenous infusion of midazolam between generalized and partial refractory convulsive status epilepticus.

  15. Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities

    Science.gov (United States)

    El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.

    2015-01-01

    Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.

  16. Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

    Science.gov (United States)

    Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2016-01-15

    The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies.

  17. Temporal Lobe Epilepsy after Refractory Status Epilepticus: An Illustrative Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    J. Gordon Boyd

    2012-01-01

    Full Text Available New onset refractory status epilepticus (NORSE is a relatively newly defined disease entity, where otherwise healthy individuals develop unrelenting seizures that do not respond to conventional anticonvulsant therapy and may require months of therapy with anesthetic drugs. We have described a case of NORSE who subsequently developed mesial temporal lobe sclerosis (MTS and recurrent temporal lobe seizures. We discuss the possible pathophysiological mechanisms by which refractory seizures may contribute to the development of temporal lobe epilepsy (TLE.

  18. Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

    Science.gov (United States)

    Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2016-01-15

    The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. PMID:26681545

  19. Contributions of Astrocytes to Epileptogenesis Following Status Epilepticus: Opportunities for Preventive Therapy?

    OpenAIRE

    Gibbons, M.B.; Smeal, R.M.; Takahashi, D.K.; Vargas, J.R.; Wilcox, K.S.

    2012-01-01

    Status epilepticus (SE) is a life threatening condition that often precedes the development of epilepsy. Traditional treatments for epilepsy have been focused on targeting neuronal mechanisms contributing to hyperexcitability, however, approximately 30% of patients with epilepsy do not respond to existing neurocentric pharmacotherapies. A growing body of evidence has demonstrated that profound changes in the morphology and function of astrocytes accompany SE and persist in epilepsy. Astrocyte...

  20. Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

    OpenAIRE

    Trinka, Eugen; Höfler, Julia; Zerbs, Alexander; Brigo, Francesco

    2014-01-01

    Introduction The effectiveness of valproate (VPA) in the treatment of focal and generalized epilepsies is well established. The drug has a wide spectrum of action, good tolerability, and has been available as an injectable formulation since 1993. Despite the lack of class A evidence, it has been used extensively in various forms of status epilepticus (SE). Aim Our aim was to present a systematic review of data from randomized and non-randomized controlled trials to evaluate the efficacy and s...

  1. Current therapeutic status for generalized status epilepticus%全面性癫痫持续状态的治疗现状

    Institute of Scientific and Technical Information of China (English)

    黎黎; 张洪

    2013-01-01

    全面性癫痫持续状态是癫痫持续状态中最严重的类型,是神经科一种急诊。本文就近年来有关全面性癫痫持续状态的流行病学、病因、药物治疗的研究现状进行阐述。%Generalized status epilepticus is one of the most serious types of status epilepticus, and it is an emergency condition in neurology department. This article reviewed currently research about epidemiology, etiology, and drug treatment of generalized status epilepticus.

  2. State and parameter estimation of a neural mass model from electrophysiological signals during the status epilepticus.

    Science.gov (United States)

    López-Cuevas, Armando; Castillo-Toledo, Bernardino; Medina-Ceja, Laura; Ventura-Mejía, Consuelo

    2015-06-01

    Status epilepticus is an emergency condition in patients with prolonged seizure or recurrent seizures without full recovery between them. The pathophysiological mechanisms of status epilepticus are not well established. With this argument, we use a computational modeling approach combined with in vivo electrophysiological data obtained from an experimental model of status epilepticus to infer about changes that may lead to a seizure. Special emphasis is done to analyze parameter changes during or after pilocarpine administration. A cubature Kalman filter is utilized to estimate parameters and states of the model in real time from the observed electrophysiological signals. It was observed that during basal activity (before pilocarpine administration) the parameters presented a standard deviation below 30% of the mean value, while during SE activity, the parameters presented variations larger than 200% of the mean value with respect to basal state. The ratio of excitation-inhibition, increased during SE activity by 80% with respect to the transition state, and reaches the lowest value during cessation. In addition, a progression between low and fast inhibitions before or during this condition was found. This method can be implemented in real time, which is particularly important for the design of stimulation devices that attempt to stop seizures. These changes in the parameters analyzed during seizure activity can lead to better understanding of the mechanisms of epilepsy and to improve its treatments.

  3. New Onset Refractory Status Epilepticus as an Unusual Presentation of a Suspected Organophosphate Poisoning

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    Shahan Waheed

    2014-01-01

    Full Text Available New onset refractory status epilepticus (NORSE is a new entity in medical literature. It has different infectious and noninfectious etiologies showing a devastating impact onto the clinical outcome of patients. Therapy with anaesthetic and antiepileptic agents often fails to improve the condition, unless the primary cause is rectified. Here is presented the case of a young female with a history of depression who after a recent bereavement came to the Emergency Department of Aga Khan University Hospital with complaints of drowsiness that lasted for few hours. Though she had no history of organophosphate poisoning, her physical examination and further investigations were suggestive of the diagnosis. During her hospital stay, she developed refractory status epilepticus. Her seizures did not respond to standard antiepileptic and intravenous anesthetic agents and subsided only after intravenous infusion of atropine for a few days. Organophosphate poisoning is a very common presentation in the developing world and the associated status epilepticus poses a devastating problem for emergency physicians. In patients with suspected organophosphate poisoning with favoring clinical exam findings, the continuation of atropine intravenous infusion can be a safe option to abate seizures.

  4. Microglial ROS production in an electrical rat post-status epilepticus model of epileptogenesis.

    Science.gov (United States)

    Rettenbeck, Maruja L; von Rüden, Eva-Lotta; Bienas, Silvia; Carlson, Regina; Stein, Veronika M; Tipold, Andrea; Potschka, Heidrun

    2015-07-10

    Reactive oxygen species and inflammatory signaling have been identified as pivotal pathophysiological factors contributing to epileptogenesis. Considering the development of combined anti-inflammatory and antioxidant treatment strategies with antiepileptogenic potential, a characterization of the time course of microglial reactive oxygen species generation during epileptogenesis is of major interest. Thus, we isolated microglia cells and analyzed the generation of reactive oxygen species by flow cytometric analysis in an electrical rat post-status epilepticus model. Two days post status epilepticus, a large-sized cell cluster exhibited a pronounced response with excessive production of reactive oxygen species upon stimulation with phorbol-myristate-acetate. Neither in the latency phase nor in the chronic phase with spontaneous seizures a comparable cell population with induction of reactive oxygen species was identified. We were able to demonstrate in the electrical rat post-status-epilepticus model, that microglial ROS generation reaches a peak after the initial insult, is only marginally increased in the latency phase, and returns to control levels during the chronic epileptic phase. The data suggest that a combination of anti-inflammatory and radical scavenging approaches might only be beneficial during a short time window after an epileptogenic brain insult.

  5. Study on etiology and treatment of convulsive status epilepticus in children

    Directory of Open Access Journals (Sweden)

    Dong LI

    2015-11-01

    Full Text Available The clinical data of 182 children with convulsive status epilepticus (CSE were analyzed. There were 21 cases with refractory status epilepticus (RSE and 161 cases with non-refractory status epilepticus (non-RSE. Etiological factors mainly included epilepsy in 54 cases, intracranial infection in 49 cases, and complex febrile seizure in 44 cases. In the ictal stage, 102 cases were treated with clonazepam by intravenous injection, 54 cases with diazepam by intravenous injection, 46 cases with midazolam by intravenous injection, 36 cases with phenobarbital by muscular injection, and 32 cases with 6.5% chloral hydrate by nosal feeding or clyster. The etiology of CSE in children is various. Epilepsy, intracranial infection and complex febrile seizure are the main causes. Poor prognosis and high mortality often occur in RSE caused by severe viral encephalitis. So the fundamental principle of treatment is to control CSE quickly and avoid the damage of brain and other important organs. DOI: 10.3969/j.issn.1672-6731.2015.11.009

  6. Mitochondrial and nuclear changes in hippocampal neurons in a lithium-pilocarpine-induced status epilepticus rat model

    Institute of Scientific and Technical Information of China (English)

    Shuhai Tang; Li Zhang; Jianying Sun; Xiaojun Pan

    2009-01-01

    BACKGROUND: Mitochondrial damage plays a key role in neuronal damage.OBJECTIVE: To observe ultrastructural damage to mitochondria and nuclei, as well as caspase-3 expression, in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats.DESIGN, TIME AND SETTING: The neuropathological, randomized, controlled study was performed at the Animal Experimental Center, Shandong University, China in May 2008.MATERIALS: A total of 75 healthy, adult, male, Wistar rats were randomly assigned into model (n = 45) and control (n = 30) groups. Lithium-pilocarpine (Sigma, USA) was used in this study.METHODS: Rats in the model group were intraperitoneally injected with lithium chloride (3 mEq/kg),and 24 hours later with pilocarpine (45 mg/kg), to induce seizures for 2 hours. Rats in the control group were intraperitoneally infused with the same volume of saline. Rat hippocampal CA3 tissue was obtained at 3, 12, and 24 hours following status epilepticus.MAIN OUTCOME MEASURES: Neuronal changes were observed under an optical microscope. Ultrastructural changes in mitochondria and nuclei were observed using an electron microscope.caspase-3 mRNA levels were quantified by semiquantitative RT-PCR.RESULTS: After 3 hours of status epilepticus, mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy. Nuclei with marginated chromatin were observed after 24 hours status epilepticus. RT-PCR results demonstrated increased caspase-3 expression at 12 hours, and significantly increased expression at 24 hours following termination of status epilepticus. This was in accordance with acidophilia occurrence, as indicated by hematoxylin-eosin staining, and time of ultrastructural damage to nuclei.CONCLUSION: In lithium-pilocarpine-induced status epilepticus rat models, ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages, followed by increased caspase-3 expression and nuclear changes. These results suggested

  7. Interleukin-1 receptor is a target for adjunctive control of diazepam-refractory status epilepticus in mice.

    Science.gov (United States)

    Xu, Zheng-Hao; Wang, Yi; Tao, An-Feng; Yu, Jie; Wang, Xiao-Yu; Zu, Yun-Yun; Zhang, Shi-Hong; Chen, Zhong

    2016-07-22

    Proinflammatory cytokine interleukin-1 beta (IL-1β) may accumulate in the brain during status epilepticus, but whether it contributes to the progressive refractoriness of SE remains unclear. By using a kainic acid-induced SE mice model, we tested whether pharmacological blockade or knock-out of interleukin-1 receptor type 1 (IL-1R1) could influence the diazepam-refractory phenomenon of prolonged SE. We confirmed diazepam failed to terminate prolonged SE (allowed to continue for 40min before diazepam administration). The expression level of IL-1β in the hippocampus during prolonged SE was significantly higher than that of baseline. Interestingly, prolonged SE was not diazepam-refractory in IL-1R1 knock-out mice. Moreover, administration of interleukin-1 receptor antagonist (IL-1RA) combined with diazepam terminated established prolonged SE, while IL-1RA alone is not capable to terminate prolonged SE. On the contrary, administration of recombinant human IL-1β weakens the efficacy of diazepam by prolonging its latency to terminate non-prolonged SE. Thus, the present study provides direct evidence that accumulated IL-1β contributed to the diazepam refractoriness of prolonged SE, and suggests that interleukin-1 receptor is a target for adjunctive control of diazepam-refractory SE. PMID:27133574

  8. The pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus

    Science.gov (United States)

    Chamberlain, James M.; Capparelli, Edmund V.; Brown, Kathleen M.; Vance, Cheryl W.; Lillis, Kathleen; Mahajan, Prashant; Lichenstein, Richard; Stanley, Rachel M.; Davis, Colleen O.; Gordon, Stephen; Baren, Jill M.; van den Anker, John N.

    2011-01-01

    Objective[mh2] To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE. Study design Ten hospitals in the Pediatric Emergency Care Applied Research Network (PECARN) enlisted patients 3 months to 17 years with convulsive SE (STATUS) or for a traditional PK study (ELECTIVE). Sparse sampling was used for STATUS and intensive sampling for ELECTIVE. Noncompartmental analyses were performed on ELECTIVE, and served to nest compartmental population PK analysis for both cohorts. Results 48 STATUS and 15 ELECTIVE patients were enrolled. Median age was 7 years, 2 months. The population PK parameters were: clearance 1.2 mL/min/kg, half-life 16.8 hours, volume of distribution 1.5 L/kg. Based on the PK model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations above 30–50 ng/mL for 6–12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg. Conclusions Lorazepam PK in convulsive status epilepticus is similar to previous PK measured in pediatric patients with cancer, except for longer half-life and similar to adult PK parameters except for increased clearance. PMID:22050870

  9. Impact of the NCAM derived mimetic peptide plannexin on the acute cellular consequences of a status epilepticus

    DEFF Research Database (Denmark)

    Zellinger, Christina; Hadamitzky, Martin; Bock, Elisabeth;

    2011-01-01

    Plannexin represents a NCAM-derived peptide mimicking trans-homophilic NCAM interaction, which proved to exert neuroprotective effects in vitro. The effect of plannexin was evaluated in a rat status epilepticus model. As expected, prolonged seizure activity resulted in a pronounced cell loss...... in hippocampal subregions. The comparison between the vehicle- and plannexin-treated animals with status epilepticus did not reveal neuroprotective effects of plannexin on mature neurons. However, treatment with plannexin partially prevented the reduction in the number of doublecortin-labeled neuronal progenitor...... cells, which was evident 48h following status epilepticus. In conclusion, the data might give first evidence that plannexin can protect immature neurons in vivo. Future studies are necessary to evaluate whether disease-modifying or preventive effects are observed in models of epileptogenesis....

  10. The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-status epilepticus model

    DEFF Research Database (Denmark)

    Russmann, Vera; Seeger, Natalie; Zellinger, Christina;

    2013-01-01

    Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status epilepticus model. Cintrofin prevented long-term alterations...... in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute status epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity....... Whereas status epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data...

  11. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

    Science.gov (United States)

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

    2015-02-01

    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients.

  12. Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus.

    Science.gov (United States)

    Kang, Bong Su; Jung, Keun-Hwa; Shin, Jeong-Won; Moon, Jang Sup; Byun, Jung-Ick; Lim, Jung-Ah; Moon, Hye Jin; Kim, Young-Soo; Lee, Soon-Tae; Chu, Kon; Lee, Sang Kun

    2015-05-01

    General anesthetic-induced coma therapy has been recommended for the treatment of refractory status epilepticus (RSE). However, the influence of electroencephalographic (EEG) burst suppression (BS) on outcomes still remains unclear. This study investigated the impact of intravenous anesthetic-induced BS on the prognosis of RSE using a retrospective analysis of all consecutive adult patients who received intravenous anesthetic treatment for RSE at the Seoul National University Hospital between January 2006 and June 2011. Twenty-two of the 111 episodes of RSE were enrolled in this study. Of the 22 RSE patients, 12 (54.5%) were women and 18 (81.4%) exhibited generalized convulsive status epilepticus. Sixteen patients (72.7%) were classified as having acute symptomatic etiology, including three patients with anoxic encephalopathy, and others with remote symptomatic etiology. Only two patients (9.1%) had a favorable Status Epilepticus Severity Score (0-2) at admission. All patients received midazolam (MDZ) as a primary intravenous anesthetic drug for RSE treatment; three (13.6%) received MDZ and propofol, and one (4.5%) received MDZ and pentobarbital. The rates of mortality and poor outcome at discharge were 13.6% (n=3) and 54.5% (n=12), respectively. While BS was achieved in six (27.5%) patients, it was not associated with mortality or poor outcome. Induced BS was associated with prolonged hospital stay in subgroup analysis when excluding anoxic encephalopathy. Our results suggest that induction of BS for treating RSE did not affect mortality or outcome at discharge and may lead to an increased length of hospital stay.

  13. Caffeic acid phenethyl ester prevents apoptotic cell death in the developing rat brain after pentylenetetrazole-induced status epilepticus.

    Science.gov (United States)

    Yiş, Uluç; Topçu, Yasemin; Özbal, Seda; Tuğyan, Kazım; Bayram, Erhan; Karakaya, Pakize; Yilmaz, Osman; Kurul, Semra Hız

    2013-11-01

    Population-based studies suggest that seizure incidence is highest during the first year of life, and early-life seizures frequently result in the development of epilepsy and behavioral alterations later in life. The early-life insults like status epilepticus often lead to epileptogenesis, a process in which initial brain injury triggers cascades of molecular, cellular, and network changes and eventually spontaneous seizures. Caffeic acid phenethyl ester is an active component of propolis obtained from honeybees and has neuroprotective properties. The aim of this study was to investigate whether caffeic acid phenethyl ester exerts neuroprotective effects on the developing rat brain after status epilepticus. Twenty-one dams reared Wistar male rats, and 21-day-old rats were divided into three groups: control group, pentylenetetrazole-induced status epilepticus group, and caffeic acid phenethyl ester-treated group. Status epilepticus was induced on the first day of experiment. Caffeic acid phenethyl ester injections (30 mg/kg intraperitoneally) started 40 min after the tonic phase of status epilepticus was reached, and the injections of caffeic acid phenethyl ester were repeated over 5 days. Rats were sacrificed, and brain tissues were collected on the 5th day of experiment after the last injection of caffeic acid phenethyl ester. Apoptotic cell death was evaluated. Histopathological examination showed that caffeic acid phenethyl ester significantly preserved the number of neurons in the CA1, CA3, and dentate gyrus regions of the hippocampus and the prefrontal cortex. It also diminished apoptosis in the hippocampus and the prefrontal cortex. In conclusion, this experimental study suggests that caffeic acid phenethyl ester administration may be neuroprotective in status epilepticus in the developing rat brain.

  14. Efficacy and Safety of Intravenous Sodium Valproate in Convulsive Status Epilepticus in Children in Shahid Sadoughi Hospital

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    Razieh FALLAH

    2012-06-01

    Full Text Available How to Cite this Article: Fallah R, Yadegari Y, Salmani Nodushan M. Efficacy and Safety of Intravenous Sodium Valproate in Convulsive Status Epilepticus in Children in Shahid Sadoughi Hospital. Iran. J. Child. Neurol 2012;6(2:39-44. Objective Status epilepticus (SE is the most common pediatric neurologic emergency with high mortality and morbidity. There is no consensus on the drug of choice in the treatment of children. The purpose of this study was to evaluate the clinical efficacy and safety of intravenous sodium valproate as a third-line drug in the treatment of generalized convulsive SE of children. Materials & Methods In a retrospective study, medical records of those children who were admitted to Shahid Sadoughi Hospital of Yazd due to refractory generalized convulsive SE and were treated by intravenous sodium valproate as a third-line drug from 2009 to 2011 were evaluated. Results Six girls and five boys with a mean age of 5.12 ± 1.2 years (range: 3 - 9.6 years were evaluated. Intravenous valproate was effective for cessation of seizures in seven patients (63.6 %. The mean dose of valproate for stopping seizures was 27.1 ± 1.4 mg/kg/day. Children whose seizures were controlled by sodium valproate were older than non- responsive children (mean± SD: 4.8 ± 1.2 years vs. 3.1 ± 0.43 years, p= 0.03 and they also had shorter ICU stay days (mean± SD: 2.6 ± 1.4 days vs. 5.6 ± 2.8 days, p= 0.01. Two children had mild and transient nausea and vomiting. None of them had cardiopulmonary or severe paraclinical side effects. Conclusion Intravenous sodium valproate may be used as an effective and safe third-line antiepileptic drug in the treatment of pediatric generalized convulsive status epilepticus.References Raj D, Gulati S, Lodha R. Status epilepticus. Indian J Pediatr 2011;78(2:219-26. Shearer P, Riviello J. Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols. Emerg Med Clin North Am 2011

  15. Status Epilepticus Due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell Transplant Recipient

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    Poorvi Chordia

    2013-12-01

    Full Text Available Reactivation of human herpes virus-6 (HHV-6 after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy.  With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.

  16. Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8-Year-Old Child.

    Science.gov (United States)

    Bradley, Lucas; Bahgat, Diaa; Sharp, Gregory; Willis, Erin; Ocal, Eylem; Albert, Gregory; Serletis, Demitre

    2015-10-01

    We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure-free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies. PMID:26552284

  17. 癫痫持续状态的治疗%Management of status epilepticus

    Institute of Scientific and Technical Information of China (English)

    丁成赟; 李志梅

    2007-01-01

    @@ 癫痫持续状态(status epilepticus,SE)是一种以反复或持续的癫痫发作为特征的病理状况,据报道SE的发病率为18.1/10万~41.0/10万[1-3].其中,全面惊厥性SE具有较高的致残率和病死率,为神经科的急症之一,一旦发生SE就应该紧急治疗.

  18. Diagnosis and interpretation of EEG on non-convulsive status epilepticus

    Directory of Open Access Journals (Sweden)

    Xiao-gang KANG

    2015-11-01

    Full Text Available It is difficult to diagnose non-convulsive status epilepticus (NCSE clinically because of the complicated etiology and various clinical and electroencephalographic features of NCSE without a universally accepted definition. Although the diagnosis of NCSE relies largely on electroencephalogram (EEG findings, the determination of NCSE on EEG is inevitably subjective, and the EEG changes of most patients is lack of specificity. As the diagnosis of NCSE is related to clinical and electroencephalographic manifestations, diagnostic criteria for NCSE should take into account both clinical and electroencephalographic features, and their response to antiepileptic drugs (AEDs. DOI: 10.3969/j.issn.1672-6731.2015.11.005

  19. Focal status epilepticus: follow-up by perfusion- and diffusion MRI

    Energy Technology Data Exchange (ETDEWEB)

    El-Koussy, M.; Loevblad, K.O.; Kiefer, C.; Schroth, G. [Department of Neuroradiology, University of Bern, Inselspital (Switzerland); Mathis, J.; Stepper, F. [Department of Neurology, University of Bern, Inselspital (Switzerland)

    2002-03-01

    Diffusion-weighted MRI demonstrated bright right temporoparietal cortex, right hippocampus, and left cerebellum in a 63-year-old female suffering a focal convulsive status epilepticus. Hyperperfusion was noted in the right temporoparietal region. Two days later, a tendency to normalization of most of the diffusion and perfusion changes was noted, apart from the right hippocampus which became brighter on diffusion- and T2-weighted images. On the tenth day the apparent diffusion coefficient was slightly elevated, getting brighter on T2-weighted images with suspected mild post-contrast enhancement. We postulate that the discharging right hippocampus suffered cytotoxic edema, which later progressed to cell damage. (orig.)

  20. Nonconvulsive Status Epilepticus Complicating Epstein-Barr Virus Encephalitis in a Child

    Directory of Open Access Journals (Sweden)

    Filippo Greco

    2014-01-01

    Full Text Available Children with acute encephalopathy show prolonged electrographic seizure activity consistent with nonconvulsive status epilepticus (NCSE. Pediatric NCSE is a heterogeneous clinical entity with poor outcome and different etiologies, including central nervous system infection, stroke, toxic-metabolic syndrome, and epileptic syndrome. We report a 4-year-old girl with seizure and behavioral changes in whom the analysis of cerebrospinal fluid by polymerase chain reaction was positive for Epstein-Barr virus. We emphasize the importance of electroencephalography (EEG, and particularly, of continuous EEG monitoring for early recognition and appropriate treatment of this condition.

  1. Severe depression as the sole symptom of affective focal status epilepticus.

    Science.gov (United States)

    Dimitriadis, Konstantinos; Pfefferkorn, Thomas; Noachtar, Soheyl

    2014-05-14

    Depression as well as fear, joy and anger have been described as the semiological features of focal epileptic seizures. When emotions present as the sole symptoms of epileptic seizures, they may easily be misdiagnosed as a psychiatric disorder. We describe a patient with affective focal status epilepticus, secondary to limbic encephalitis, in which depression was the only clinical manifestation. Through EEG correlates the epileptic nature of depression could be proven. Furthermore, we discuss the association between epilepsy and depression, as well as the link between ictal depression and suicidal rates.

  2. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    Directory of Open Access Journals (Sweden)

    Gentle Sunder Shrestha

    2015-01-01

    Full Text Available Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion.

  3. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    Science.gov (United States)

    Shrestha, Gentle Sunder; Joshi, Pankaj; Chhetri, Santosh; Karn, Ragesh; Acharya, Subhash Prasad

    2015-01-01

    Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion. PMID:25983437

  4. Slow pseudoperiodic lateralized epileptiform discharges in nonconvulsive status epilepticus in a patient with cerebral palsy and a large central meningioma

    Directory of Open Access Journals (Sweden)

    Y.Z. Imam

    2014-01-01

    Full Text Available The presence of cerebral palsy and that of slow growing brain tumors are risk factors for convulsive and nonconvulsive status epilepticus. Nonconvulsive status epilepticus (NCSE needs electroencephalographic (EEG monitoring to be confirmed as it may be clinically subtle. Furthermore, it may present with a variety of ictal EEG morphologies. We report a case of a patient with cerebral palsy and a large central meningioma. Electroencephalogram showed a slow pattern of periodic lateralized epileptiform discharges (PLEDs (a pattern considered as being situated in the ictal–interictal continuum on an alpha background. The patient was treated for NCSE successfully with benzodiazepines followed by up-titration of his antiepileptic drug doses.

  5. An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries.

    Science.gov (United States)

    Hassan, Haseeb; Rajiv, Keni Ravish; Menon, Ramshekhar; Menon, Deepak; Nair, Muralidharan; Radhakrishnan, Ashalatha

    2016-06-01

    Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common

  6. Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study.

    Science.gov (United States)

    Scorza, Fulvio Alexandre; Arida, Ricardo Mario; Priel, Margareth Rose; Calderazzo, Lineu; Cavalheiro, Esper Abrão

    2002-06-01

    Status epilepticus (SE) is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG) procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO) using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%), caudate-putamen (+30.6%), frontoparietal cortex (+32.2%), amygdala (+31.7%), entorrinal cortex (+28.2%), thalamic nucleus (+93.5%), pre-tectal area (+50.1%) and substantia nigra (+50.3%) when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

  7. Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

    Directory of Open Access Journals (Sweden)

    Scorza Fulvio Alexandre

    2002-01-01

    Full Text Available Status epilepticus (SE is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%, caudate-putamen (+30.6%, frontoparietal cortex (+32.2%, amygdala (+31.7%, entorrinal cortex (+28.2%, thalamic nucleus (+93.5%, pre-tectal area (+50.1% and substantia nigra (+50.3% when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

  8. A Case Of Primary Central Nervous System Vasculitis Who Presented With Status Epilepticus

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    Sırma Geyik

    2014-12-01

    Full Text Available Primary central nervous system vasculitis (PCNV is limited with central nervous system and rare vasculitis that mostly seen in middle-aged men. PCNV vasculitis is usually presented that headache, dementia, stroke and multifocal common neurological symptoms. PCNV especially involves small medium-sized leptomeningeal and cortical arteries. 43 years old male patient who have been progressive forgetfulness and headache for 3 years. He applied with recurrent that before starting right focal and than sprawling whole body which generalized tonic-clonic seizures to us. During management that he was transfered to the intensive care unit due to status epilepticus (SE. Later than we found right hemiparesis, motor aphasia and right babinski positivity in neurologic examination. Diffusion restriction was revealed in left MCA territory in diffusion magnetic resonance imaging(MRI. EEG showed two types abnormality that a slow background ritm and epileptiform activity. Biochemistry of blood, complete blood count, blood sedimentation rate, CRP and markers of vasculitis were found in the normal range. Cerebral anjiography revealed that irregularities in the distal vascular areas and fusiform aneurysm at the top of basilar artery. He was consulted with rheumatology and diagnosed central nervous system vasculitis with the existing findings. Biopsy couldn't be taken from the brain to verify the diagnosis. Finally, we applied treatment that pulse steroid and cyclophosphamide to patient. This case has been presented due to emphasize that PCNV rarely may play a role in the etiology of recurrent stroke and status epilepticus.

  9. Ischemic-hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus.

    Science.gov (United States)

    Lucchi, Chiara; Vinet, Jonathan; Meletti, Stefano; Biagini, Giuseppe

    2015-08-01

    Status epilepticus (SE) is one of the recognized primary precipitating events that can lead to temporal lobe epilepsy (TLE) associated with hippocampal sclerosis. This type of epilepsy is characterized by poor response to drug treatment, often requiring surgical intervention to remove the mesial temporal regions involved in the seizure onset. However, even neurosurgery may not be completely successful. Thus, the prevention of hippocampal damage and epileptogenesis is currently evaluated as a possible alternative therapeutic approach to prevent the development of pharmacoresistant TLE. Lines of evidence suggest that ischemic-hypoxic lesions might occur in different brain regions, including the hippocampus, during SE. Especially in the hippocampal CA3 region, an ischemic-like lesion develops in the stratum lacunosum-moleculare and is mainly characterized by a loss of astrocytes and neuronal processes and increased immunostaining of pimonidazole which probes areas exposed to hypoxia. Interestingly, these mechanisms can contribute to neuronal cell loss and may be counteracted by drugs that can afford vascular protection, as in the case of ligands of the ghrelin receptor. Notably, some of the ghrelin receptor ligands possess a double edge effect, since they are anticonvulsant and vascular-protective, thus, potentially representing new tools to counteract the consequences of SE. This article is part of a Special Issue entitled "Status Epilepticus".

  10. Analysis of factors influencing admission to intensive care following convulsive status epilepticus in children.

    LENUS (Irish Health Repository)

    Tirupathi, Sandya

    2012-02-01

    OBJECTIVES: To identify clinical features and therapeutic decisions that influence admission to the Intensive Care unit (ICU) in children presenting with convulsive status epilepticus (CSE). METHODS: We evaluated 47 admissions with status epilepticus to a tertiary paediatric hospital A&E over a three year period (2003-2006). Following initial management 23 episodes required admission to ICU and 24 were managed on a paediatric ward. We compared clinical, demographic data and compliance with our CSE protocol between the ICU and ward groups. RESULTS: Median age at presentation in the ICU group was 17 months (range 3 months-11 years) compared to 46 months in the ward group (range 3 months-10 years). Fifty per cent of patients in both groups had a previous history of seizures. Median duration of pre-hospital seizure activity was 30 min in both groups. More than two doses of benzodiazepines were given as first line medication in 62% of the ICU group and 33% of the ward group. Among children admitted to ICU with CSE, 26% had been managed according to the CSE protocol, compared to 66% of children who were admitted to a hospital ward. Febrile seizures were the most common aetiology in both groups. CONCLUSION: Younger age at presentation, administration of more than two doses of benzodiazepines and deviation from the CSE protocol appear to be factors which influence admission of children to ICU. Recognition of pre-hospital administration of benzodiazepines and adherence to therapeutic guidelines may reduce the need for ventilatory support in this group.

  11. Effect of glycemic state in rats submitted to status epilepticus during development Efeito do estado glicêmico em ratos submetidos ao status epilepticus durante o desenvolvimento

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    Joselita F.C. Santiago

    2006-06-01

    Full Text Available The effect of glycemic state on status epilepticus (SE development was studied in animals of different ages, submitted to pilocarpine model of epilepsy. Groups: I- Rats with 9-day-old (P9: IA. Submitted to 1SE; IB. Saline-treated; IC. Induced- hyperglycemia; ID. Induced- hyperglycemia+SE; II- Rats submitted to three consecutive episodes of SE at P7, P8 and P9; III- Rats submitted to 1SE at P17; IV- Rats submitted to 1SE at P21. Hippocampal cell death and the expression of glucose transporter GLUT3 were analyzed in group I. The results demonstrated normoglycemia in the groups IA, IB and II, hypoglycemia in group III and hyperglycemia in group IV, showing that the glycemia during SE is age dependent. Induced hyperglycemia during SE in P9 protected the hippocampal neurons from death and both groups IC and ID presented increased GLUT3 expression, showing high glucose consumption by the hippocampus.O efeito do estado glicêmico sobre o desenvolvimento do status epilepticus (SE foi estudado em animais de diferentes idades, submetidos ao modelo de epilepsia por pilocarpina. Grupos: I- Ratos com nove dias (P9: IA- Submetidos a 1SE; IB- Tratados com salina; IC- Hiperglicemia induzida; ID- Hiperglicemia induzida+SE; II- Ratos submetidos a 3 episódios consecutivos de SE em P7, P8 e P9; III- Ratos submetidos a 1SE em P17; IV- Ratos submetidos a 1SE em P21. Foram analisados no grupo I a morte celular hipocampal e a expressão do transportador de glicose GLUT3. Os resultados mostraram haver normoglicemia nos grupos IA, IB e II, hipoglicemia no grupo III e hiperglicemia no grupo IV, sendo a glicemia durante o SE, idade dependente. A hiperglicemia induzida durante o SE em P9 protegeu neurônios hipocampais e os grupos IC e ID apresentaram expressão aumentada de GLUT3, mostrando aumento no consumo de glicose pelo hipocampo.

  12. Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning

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    James eReynolds

    2015-03-01

    Full Text Available Exposure of the brain to brief, non-harmful seizures can activate protective mechanisms that temporarily generate a damage-refractory state. This process, termed epileptic tolerance, is associated with large-scale down-regulation of gene expression. Polycomb group proteins are master controllers of gene silencing during development that are re-activated by injury to the brain. Here we explored the transcriptional response of genes associated with polycomb repressor complex (PRC 1 (Ring1A and Ring1B and Bmi1 and PRC2 (Ezh1, Ezh2 and Suz12, as well as additional transcriptional regulators Sirt1, Yy1 and Yy2, in a mouse model of status epilepticus. Findings were contrasted to changes after status epilepticus in mice previously given brief seizures to evoke tolerance. Real-time quantitative PCR showed status epilepticus prompted an early (1 h increase in expression of several genes in PRC1 and PRC2 in the hippocampus, followed by down-regulation of many of the same genes at later times points (4 , 8 and 24 h. Spatio-temporal differences were found among PRC2 genes in epileptic tolerance, including increased expression of Ezh2, Suz12 and Yy2 relative to the normal injury response to status epilepticus. In contrast, PRC1 complex genes including Ring 1B and Bmi1 displayed differential down-regulation in epileptic tolerance. The present study characterizes polycomb group gene expression following status epilepticus and shows prior seizure exposure produces select changes to PRC1 and PRC2 composition that may influence differential gene expression in epileptic tolerance.

  13. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    OpenAIRE

    Gentle Sunder Shrestha; Pankaj Joshi; Santosh Chhetri; Ragesh Karn; Subhash Prasad Acharya

    2015-01-01

    Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epile...

  14. Nonconvulsive status epilepticus associated with periodic lateralized epileptiform discharges in a patient with syphilis

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    Xin Yu

    2016-09-01

    Full Text Available Nonconvulsive status epilepticus (NCSE has been increasingly recognized as a cause of impaired level of consciousness in the ICU and emergency rooms. The confirmation of NCSE is largely based on the EEG, given the nonspecific and pleomorphic clinical manifestations. Debate remains over electroencephalograms (EEG criteria for NCSE. Periodic lateralized epileptiform discharges (PLEDs, have sparked controversy with regard to being part of the ictal vs. interictal spectrum. We report a case of a patient with syphilis who had cognitive decline and damaged consciousness with PLEDs and T2 hyperintensity at temporal and occipital lobe in MRI. After antiepileptic treatment only, his consciousness improved markedly together with the EEG in few days, while the change of MRI was still serious. In this case PLEDs is the sign of NCSE and change of MRI is limbic encephalitis (LE. This report discusses the association of PLEDs and NCSE, and supports the concept of PLEDs as an ictal pattern in some condition.

  15. Infodemiology of status epilepticus: A systematic validation of the Google Trends-based search queries.

    Science.gov (United States)

    Bragazzi, Nicola Luigi; Bacigaluppi, Susanna; Robba, Chiara; Nardone, Raffaele; Trinka, Eugen; Brigo, Francesco

    2016-02-01

    People increasingly use Google looking for health-related information. We previously demonstrated that in English-speaking countries most people use this search engine to obtain information on status epilepticus (SE) definition, types/subtypes, and treatment. Now, we aimed at providing a quantitative analysis of SE-related web queries. This analysis represents an advancement, with respect to what was already previously discussed, in that the Google Trends (GT) algorithm has been further refined and correlational analyses have been carried out to validate the GT-based query volumes. Google Trends-based SE-related query volumes were well correlated with information concerning causes and pharmacological and nonpharmacological treatments. Google Trends can provide both researchers and clinicians with data on realities and contexts that are generally overlooked and underexplored by classic epidemiology. In this way, GT can foster new epidemiological studies in the field and can complement traditional epidemiological tools.

  16. Short-term mortality and prognostic factors related to status epilepticus

    Directory of Open Access Journals (Sweden)

    Fernando Gustavo Stelzer

    2015-08-01

    Full Text Available Objective Status epilepticus (SE is associated with significant morbidity and mortality, and there is some controversy concerning predictive indicators of outcome. Our main goal was to determine mortality and to identify factors associated with SE prognosis. Method This prospective study in a tertiary-care university hospital, included 105 patients with epileptic seizures lasting more than 30 minutes. Mortality was defined as death during hospital admission. Results The case-fatality rate was 36.2%, which was higher than in previous studies. In univariate analysis, mortality was associated with age, previous epilepsy, complex focal seizures; etiology, recurrence, and refractoriness of SE; clinical complications, and focal SE. In multivariate analysis, mortality was associated only with presence of clinical complications. Conclusions Mortality associated with SE was higher than reported in previous studies, and was not related to age, specific etiology, or SE duration. In multivariate analysis, mortality was independently related to occurrence of medical complications.

  17. Opercular myoclonic-anarthric status epilepticus: A report of two cases

    Directory of Open Access Journals (Sweden)

    Janapareddy Vijaya Bhaskara Rao

    2013-01-01

    Full Text Available Opercular myoclonic-anarthric status epilepticus (OMASE is an uncommon disorder of diverse etiology. This condition is characterized by fluctuating cortical dysarthria associated with epileptic myoclonus involving glossopharyngeal musculature bilaterally. We report two cases of OMASE of vascular etiology in adults. In both patients, ictally clonic expression was consistent with epilepsia partialis continua and bilateral, symmetrical involvement of soft palate in one patient and tongue, lips, chin and inferior jaw in both patients due to bilateral projections of the inferior corticonuclear pathways. The inferior rolandic area of dominant and high frontal region in non-dominant hemispheres were involved by an epileptogenic lesion of vascular etiology, which was confirmed by magnetic resonance imaging of brain and single photon emission computerized tomography. Carotid Doppler study showed thrombosis of internal carotid artery in both patients, suggestive of an embolic origin. Early recognition of OMASE is important for early management of carotid occlusive disease.

  18. Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome.

    Science.gov (United States)

    van den Munckhof, Bart; de Vries, Evelien E; Braun, Kees P J; Boss, H Myrthe; Willemsen, Michèl A; van Royen-Kerkhof, Annet; de Jager, Wilco; Jansen, Floor E

    2016-02-01

    We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy.

  19. Status epilepticus associated with initiation of theophylline in an elderly patient with diabetic ketoacidosis

    Directory of Open Access Journals (Sweden)

    Chung-Hsing Chou

    2007-01-01

    Full Text Available An 80-year-old man with a history of Type 2 diabetes mellitus was hospitalized due to generalized convulsive status epilepticus. Initially, hyperglycemia and ketoacidosis were diagnosed, but his seizures were refractory to the medical treatment. Additionally, a high level of serum theophylline (29.1 mg/mL was detected. Following detoxification of theophylline by oral activated charcoal, the patient regained consciousness and was free from seizures without antiepileptic drug treatment. Brain magnetic resonance imaging revealed subacute subdural hematomas at the bilateral occipital hemispheres. This case suggests that theophylline toxicity may be a predisposing factor for seizures in patients with a history of traumatic brain injury in spite of the presence of diabetic ketoacidosis that may have an anticonvulsant action.

  20. Serum inflammatory mediators correlate with disease activity in electrical status epilepticus in sleep (ESES) syndrome.

    Science.gov (United States)

    van den Munckhof, Bart; de Vries, Evelien E; Braun, Kees P J; Boss, H Myrthe; Willemsen, Michèl A; van Royen-Kerkhof, Annet; de Jager, Wilco; Jansen, Floor E

    2016-02-01

    We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy. PMID:26666401

  1. Phase-locking of epileptic spikes to ongoing delta oscillations in non-convulsive status epilepticus.

    Science.gov (United States)

    Hindriks, Rikkert; Meijer, Hil G E; van Gils, Stephan A; van Putten, Michel J A M

    2013-01-01

    The EEG of patients in non-convulsive status epilepticus (NCSE) often displays delta oscillations or generalized spike-wave discharges. In some patients, these delta oscillations coexist with intermittent epileptic spikes. In this study we verify the prediction of a computational model of the thalamo-cortical system that these spikes are phase-locked to the delta oscillations. We subsequently describe the physiological mechanism underlying this observation as suggested by the model. It is suggested that the spikes reflect inhibitory stochastic fluctuations in the input to thalamo-cortical relay neurons and phase-locking is a consequence of differential excitability of relay neurons over the delta cycle. Further analysis shows that the observed phase-locking can be regarded as a stochastic precursor of generalized spike-wave discharges. This study thus provides an explanation of intermittent spikes during delta oscillations in NCSE and might be generalized to other encephathologies in which delta activity can be observed.

  2. Pilocarpine-induced status epilepticus in rats involves ischemic and excitotoxic mechanisms.

    Directory of Open Access Journals (Sweden)

    Paolo Francesco Fabene

    Full Text Available The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE. Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology.

  3. Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

    Science.gov (United States)

    Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology. PMID:17971868

  4. Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.

    Science.gov (United States)

    McCarren, Hilary S; McDonough, John H

    2016-06-01

    Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit. PMID:27258770

  5. Effect of lithium-pilocarpine-induced status epilepticus on ultrasonic vocalizations in the infant rat pup.

    Science.gov (United States)

    López-Meraz, Maria-Leonor; Medel-Matus, Jesus-Servando; Morgado-Valle, Consuelo; Beltrán-Parrazal, Luis; Pérez-Estudillo, César; Manzo, Jorge

    2014-02-01

    Evidence shows that febrile convulsions induced in rat pups increase ultrasonic vocalizations (USVs); however, the effect of status epilepticus (SE) induced in developing rats on USVs has not been fully investigated. The goal of this study was to analyze USVs following lithium-pilocarpine-induced SE in fourteen-day-old (P14) rat pups. The rat pups were given 3-mEq/kg lithium chloride i.p. on the day before the induction of SE, which was carried out at P14 by subcutaneous injection of 100-mg/kg pilocarpine hydrochloride; control animals were given an equal volume of lithium chloride and saline on P13 and P14, respectively. Ultrasonic vocalizations were monitored at P15, P16, and P21 with a Mini 3 Bat Detector Ultra Sound Advice (15kHz-160kHz) set at 40±4kHz and digitally recorded in WAV format using the Audacity 1.3 beta software. A clear box (60×40×30cm) split down the middle with a holed wall was used; each pup was placed alone in one compartment, whereas its dam was placed on the other cage side at room temperature. Vocalizations were recorded over a 5-minute period, converted to sonograms and spectrograms, and analyzed using the Raven software. Parameters evaluated were as follows: USV frequency, latency to the first USV, and mean USV duration. There was a significant decrease in the latency (35.5±6.9s) and duration (50.8±8.6s) of USVs after SE compared with the control group (81.9±10.8s and 78.1±9.9s, respectively). Status epilepticus affected male and female rats differentially.

  6. Continuous EEG monitoring in the evaluation of non-convulsive seizures and status epilepticus

    Directory of Open Access Journals (Sweden)

    Murthy J

    2004-10-01

    Full Text Available Non-convulsive seizures (NCSzs and non-convulsive status epilepticus (NCSE occur in a substantial proportion of patients with acute brain injury. These acute seizure disorders are often unrecognized and under-diagnosed. Seizure semiology of NCSz is too subtle clinically to be noticed. Most often, mental status impairment is the presenting feature. Changes in the functions of the thalamo-cortical system in patients with impaired consciousness can be detected by continuous EEG (cEEG monitoring. cEEG monitoring allows detection of the changes at a reversible stage, often when there are no clinical indications of such phenomena. In addition EEG provides reasonable spatial resolution and excellent temporal resolution. This makes cEEG an excellent method for supplementing single or serial recordings in the detection of NCSzs and NCSE. Recent advances in digital EEG have made cEEG monitoring in the neurological intensive care unit (NICU technically feasible. Current evidence suggests that the common clinical denominator associated with electrographic seizures or NCSzs is mental status impairment. In NCSE, the duration of ictal activity and the time of delay to diagnosis are independent predictors of poor outcome. It will be prudent to do cEEG monitoring in any patient with impaired consciousness either in the setting of acute brain injury or with no clear explanation to detect NCSzs/NCSE. Early recognition and timely intervention is likely to be associated with good outcomes.

  7. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study

    OpenAIRE

    Pugin, Deborah; Foreman, Brandon; De Marchis, Gian Marco; Fernandez, Andres; Schmidt, J. Michael; Czeisler, Barry M; Mayer, Stephan A; Agarwal, Sachin; Lesch, Christine; Lantigua, Hector; Claassen, Jan

    2014-01-01

    Introduction Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. Methods We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution...

  8. [Nonconvulsive status epilepticus due to Fentanyl intoxication in hemodialysed patients: two case reports and review of the literature].

    Science.gov (United States)

    Pogliani, Daniela; Pozzi, Annalisa; Laudi, Claudio; Rimoldi, Laura; Sogni, Elisabetta; Farfaglia, Piera; Figliola, Carmela; Jovane, Carlo; Zarcone, Davide; Caretta, Enrico

    2016-01-01

    The management of the pain therapy (ischemic pain, neoplastic pain) in hemodialysis patients has become a frequent challenge in the last years. These patients often require the prescription of major analgesic drugs such as Opioids like Fentanyl, in order to control the pain. It is necessary to pay attention to the correct dosage and to the half life of these drugs, that results prolonged in the chronic renal insufficiency. The main side effect of opioids is respiratory depression which is well known, however, up to date, there is a lack of reports about other less frequent side effects, such as epilepsy or status epilepticus, in the literature. We report two cases of chronic hemodialysed patients who developed a generalized nonconvulsive status epilepticus secondary to Fentanyl intoxication administered for the pain therapy. These cases required a synergic team management with involvement of the nephrologist, the neurologist and the intensivist. The generalized non convulsive status epilepticus could be an important and serious side effect of Fentanyl in hemodialysis patients and it is therefore necessary a close monitoring of the pain therapy in these subjects.

  9. 儿童癫(痫)持续状态研究进展%Research progress of children with status epilepticus

    Institute of Scientific and Technical Information of China (English)

    刘田田; 王艺

    2014-01-01

    Status epilepticus (SE) is one of the common medical emergencies of the pediatric age group.It may lead to serious and even irreversible neurological abnormalities,even death,if not diagnosis and treatment properly.To recognise etiology,rise factors,seizure type,treatment,outcome and the correlation between each other of children with status epilepticus are significant for management.This paper aimed to review recent epidemiological studies on children with status epilepticus,in order to provide evidences for the current clinical practice and further research.%癫(痫)持续状态是常见的小儿临床急症之一,若不及时正确诊治可导致严重甚至不可逆的神经系统损伤,重者亦可导致死亡.明确病因及危险因素、发作类型、治疗、预后等因素及其彼此之间的相关性,对疾病的正确处理至关重要.现对目前国内外关于儿童癫(痫)持续状态研究进行综述,为临床实践和研究提供依据.

  10. Does status epilepticus induced at early postnatal period change excitability after cortical epileptic afterdischarges?

    Science.gov (United States)

    Mareš, Pavel; Kubová, Hana

    2016-08-01

    Possible changes of cortical excitability after status epilepticus (SE) elicited in 12-day-old rats were studied by means of paired cortical afterdischarges (ADs). Consequences of lithium-pilocarpine status were studied in animals with implanted electrodes 3, 6, 9, 13, and 26 days after SE. Paired low-frequency stimulation with a 1-min interval was repeated after 10 min, and duration of ADs was measured. Control rats received saline instead of pilocarpine; other treatments were the same as in SE group. Postictal refractoriness (i.e., the testing response significantly shorter than the conditioning one) appeared at the age of 18 days in lithium-paraldehyde controls, whereas SE animals exhibited this phenomenon since postnatal day 21. The only significant difference between SE and lithium-paraldehyde controls was found in the second conditioning AD in the oldest group studied-it was longer in 38-day-old SE animals. Our results demonstrated moderate signs of higher excitability of SE rats in comparison with control ones long before appearance of spontaneous seizures. PMID:27346862

  11. Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

    Institute of Scientific and Technical Information of China (English)

    Hai-ju ZHANG; Ruo-peng SUN; Ge-fei LEI; Lu YANG; Chun-xi LIU

    2008-01-01

    Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods:Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis wore analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (GABAA) receptors and mitogen-activated protein kinase/extracellular sig-nal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesuifonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

  12. Treatment strategy of refractory status epilepticus%难治性痉挛性癫持续状态的治疗对策

    Institute of Scientific and Technical Information of China (English)

    杨思达

    2015-01-01

    癫发作依据持续的时程和对治疗的反应分为早期癫持续状态( early status epilepticus)、确认的癫持续状态( established status epilepticus)、难治性癫持续状态( refractory status epilepticus)和超级难治性癫持续状态( super-refractory status epilepticus)。本研究主要针对难治性及超级难治性癫的治疗策略进行系统回顾,包括致病相关因素、脑损伤的分析,指出超级难治性癫是一个重要的临床问题,有着较高的病死率和发病率。现就近期世界范围发表的文献提出的治疗方法进行评价,包括麻醉药物,抗癫药物,镁剂,吡哆醇,类固醇和免疫治疗,生酮饮食,低温疗法,神经外科干预,经颅磁刺激,迷走神经刺激,脑深部刺激,电休克疗法,脑脊液引流及其他传统药物等疗法。强调原因的识别与对因治疗的重要性,推荐难治性癫分段治疗方案及超级难治性癫的管理流程。%Status epilepticus basis for sustained duration and response to treatment can be divided into early status epilepticus,established status epilepticus,refractory status epilepticus and super-refractory status epilepticus. This article reviews the treatment approaches. Mainly conducted a systematic review for treatment strategy of refractory status epilepticus and super-refractory status epilepticus. Including pathogenic factors and cerebral damage analysis. It proposed super-refractory status epilepticus is an uncommon but important clinical problem with high mortality and morbidity rates. The published world literature on the following treatments is critically evaluated:anaesthetic a-gents,anti-epileptic drugs,magnesium infusion,pyridoxine,steroids and immunotherapy,ketogenic diet,hypothermia,e-mergency resective neurosurgery and multiple subpial transection,transcranial magnetic stimulation,vagal nerve stimula-tion,deep brain stimulation,electroconvulsive therapy,drainage of the cerebrospinal

  13. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    Science.gov (United States)

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  14. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    Science.gov (United States)

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients. PMID:26834859

  15. Status Epilepticus as a Presenting Sign of Reversible Posterior Leukoencephalopathy Syndrome in a Liver Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Seyed-Mohammadali Musavi

    2009-03-01

    Full Text Available Background: Reversible posterior leukoencephalopathy syndrome (RPLE is an increasingly recognized disorder, most commonly associated with immunosuppressive and cytotoxic agent, malignant hypertension and toxemia of pregnancy. Neurological symptoms are headache, mental and visual disturbance, and seizures. Brain MRI findings are symmetrical bilateral hyper intense areas of occipital and parietal lobes in T2-weighted magnetic resonance (MR images. This finding is reversible with prompt successful treatment which may take days to weeks for full reversal. Case Presentation: We observed a case of status epilepticus which occurred 32 days after liver transplantation in a patient on regimen consisting of Tacrolimus (FK 506. He had no history of neurologic disease or metabolic abnormalities. Typical findings of RPLE were present on brain MRI. The recurrence of seizures terminated after a few hours with adding Na-valproate to Phenytoin, Phenobarbital and Midazolam. The radiological finding of brain MRI gradually diminished after several weeks. Conclusion: A physician should be alert of seizures during early post transplant period of liver transplantation. He should bear in mind the diagnosis of RPLE and consider discontinuation of immunosuppressive drugs.

  16. Does pilocarpine-induced epilepsy in adult rats require status epilepticus?

    Directory of Open Access Journals (Sweden)

    Graciela Navarro Mora

    Full Text Available Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS and b whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22 months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy.

  17. Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

    Science.gov (United States)

    Sukhotinsky, Inna; Chan, Alexander M; Ahmed, Omar J; Rao, Vikram R; Gradinaru, Viviana; Ramakrishnan, Charu; Deisseroth, Karl; Majewska, Ania K; Cash, Sydney S

    2013-01-01

    Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR), a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.

  18. Enhanced inositide turnover in brain during bicuculline-induced status epilepticus

    Energy Technology Data Exchange (ETDEWEB)

    Van Rooijen, L.A.; Vadnal, R.; Dobard, P.; Bazan, N.G.

    1986-04-29

    Because brain inositides are enriched in the 1-stearoyl-2-arachidonoyl species, they form a likely source for the tetraenoic free fatty acids (FFA) and diacylglycerols (DG) that are accumulated during seizures. To study inositide turnover during bicuculline-induced seizures, rats were injected intraventricularly and bilaterally with 10-20 microCi /sup 32/P, mechanically ventilated and sacrificed by 6.5 KW head-focused microwave irradiation. Seizure activity was recorded by electroencephalography. Bicuculline-induced seizure activity resulted in: a) almost 50% increase in /sup 32/P labeling of phosphatidic acid (PA); phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) also increased (24% and 36%, respectively); b) no change in other lipids; and c) water-soluble phosphodiesteratic degradation products, analyzed by high voltage paper electrophoresis, increased 24% in the amount of radiotracer recovered as inositol 1,4-bisphosphate (IP2) and by 44% in the amount recovered as inositol 1,4,5-trisphosphate (IP3). These data indicate that during experimental status epilepticus the cerebral inositide cycle is accelerated: PIP2----(IP3----IP2----IP----I) + DG----PA----PI----PIP----PIP2.

  19. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy

    Directory of Open Access Journals (Sweden)

    Laxmikant S Deshpande

    2014-01-01

    Full Text Available Status epilepticus (SE is a major clinical emergency that is associated with high mortality and morbidity. SE causes significant neuronal injury and survivors are at a greater risk of developing acquired epilepsy and other neurological morbidities, including depression and cognitive deficits. Benzodiazepines and some anticonvulsant agents are drugs of choice for initial SE management. Despite their effectiveness, over 40% of SE cases are refractory to the initial treatment with two or more medications. Thus there is an unmet need of developing newer anti-SE drugs. Levetiracetam (LEV is a widely prescribed anti-epileptic drug that has been reported to be used in SE cases, especially in benzodiazepine-resistant SE or where phenytoin cannot be used due to allergic side-effects. Levetiracetam’s non-classical antiepileptic mechanisms of action, favorable pharmacokinetic profile, general lack of central depressant effects and lower incidence of drug interactions contributes to its use in SE management. This review will focus on LEV’s unique mechanism of action that makes it a viable candidate for SE treatment.

  20. Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

    Directory of Open Access Journals (Sweden)

    Inna Sukhotinsky

    Full Text Available Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR, a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.

  1. Complex partial status epilepticus%复杂部分性癫痫持续状态

    Institute of Scientific and Technical Information of China (English)

    张卫清; 石进; 吕强; 张英谦; 宋东林

    2006-01-01

    目的探讨复杂部分性癫痫持续状态(complex partial status epilepticus,CPSE)的临床表现及治疗方法.方法回顾性分析两例CPSE患者的临床发病过程、脑电图及抗癫痫治疗等资料并复习相关文献.结果两例女性患者,均为成年起病,发作持续时间为数小时至数日,均有意识障碍,伴有不同程度的精神及行为异常.发作间期脑电图表现为广泛的慢波活动及局灶性慢波发放,经抗癫痫药物治疗,均完全控制发作.结论意识障碍及精神行为异常是CPSE的特征性临床表现,脑电图异常及抗癫痫药物治疗有效有助于CPSE的确诊.

  2. Development of epileptiform excitability in the deep entorhinal cortex after status epilepticus

    Science.gov (United States)

    Bragin, Denis E.; Sanderson, Jennifer L.; Peterson, Steven; Connor, John A.; Müller, Wolfgang S.

    2009-01-01

    Epileptiform neuronal activity during seizures is observed in many brain areas, but its origins following status epilepticus (SE) are unclear. We have used the Li-low dose pilocarpine rat model of temporal lobe epilepsy (TLE) to examine early development of epileptiform activity in the deep entorhinal cortex (EC). We show that during the 3 week latent period that follows SE, an increasing percentage of neurons in EC layer 5 respond to a single synaptic stimulus with polysynaptic burst depolarizations. This change is paralleled by a progressive depolarizing shift of the IPSP reversal potential in layer 5 neurons, apparently caused by upregulation of the Cl- inward transporter NKCC1 and concurrent downregulation of the Cl- outward transporter KCC2, both changes favoring intracellular Cl- accumulation. Inhibiting Cl- uptake in the latent period restored more negative GABAergic reversal potentials and eliminated polysynaptic bursts. The changes in the Cl- transporters were highly specific to the deep entorhinal cortex. They did not occur in layers 1-3, perirhinal cortex, subiculum or dentate gyrus during this period. We propose that the changes in Cl- homeostasis facilitate hyperexcitability in the deep entorhinal cortex leading to epileptiform discharge there, which subsequently affects downstream cortical regions. PMID:19674083

  3. Status epilepticus induces increasing neuronal excitability and hypersynchrony as revealed by optical imaging.

    Science.gov (United States)

    Holtkamp, M; Buchheim, K; Elsner, M; Matzen, J; Weissinger, F; Meierkord, H

    2011-07-01

    In the wake of acquired brain insults such as status epilepticus (SE), time-dependent neuronal network alterations may occur resulting in cortical hyperexcitability and enhanced synchrony merging into chronic epilepsy. To better understand the underlying processes, we performed electrophysiological and optical imaging studies on combined hippocampal-entorhinal cortex slices. These were prepared from rats 1, 4 and 8 weeks after electrically-induced SE. Non-invasive imaging using intrinsic optical signal changes allowed detailed analysis of onset and spread patterns of seizure-like events (SLE) since coverage of the entire preparation is possible. The latency to occurrence of first SLEs after omission of Mg(2+) from the artificial cerebrospinal fluid was significantly reduced at 4 and 8 weeks after SE compared with all other groups indicating increased brain excitability. Optical imaging displayed multiregional onset and discontiguous propagation of SLEs 8 weeks after SE. Such patterns indicate neuronal hypersynchrony and are not encountered in naïve rodents in which SLEs commonly begin in the entorhinal cortex and display contiguous spread to invade adjacent regions. The electrophysiological and optical findings of the current study indicate evolving fundamental brain plasticity changes after the detrimental event predisposing to chronic epilepsy. The current results should be incorporated in any strategies aiming at prevention of chronic epilepsy.

  4. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    Science.gov (United States)

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.

  5. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

    International Nuclear Information System (INIS)

    To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. (orig.)

  6. Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus.

    Science.gov (United States)

    Wang, N; Mi, X; Gao, B; Gu, J; Wang, W; Zhang, Y; Wang, X

    2015-02-26

    Mounting evidence suggests that brain inflammation mediated by glial cells may contribute to epileptogenesis. Minocycline is a second-generation tetracycline and has potent antiinflammatory effects independent of its antimicrobial action. The present study aimed to investigate whether minocycline could exert antiepileptogenic effects in a rat lithium-pilocarpine model of temporal lobe epilepsy. The temporal patterns of microglial and astrocytic activation were examined in the hippocampal CA1 and the adjacent cortex following pilocarpine-induced status epilepticus (SE). These findings displayed that SE caused acute and persistent activation of microglia and astrocytes. Based on these findings, Minocycline was administered once daily at 45 mg/kg for 14 days following SE. Six weeks after termination of minocycline treatment, spontaneous recurrent seizures (SRS) were recorded by continuous video monitoring. Minocycline inhibited the SE-induced microglial activation and the increased production of interleukin-1β and tumor necrosis factor-α in the hippocampal CA1 and the adjacent cortex, without affecting astrocytic activation. In addition, Minocycline prevented the SE-induced neuronal loss in the brain regions examined. Moreover, minocycline significantly reduced the frequency, duration, and severity of SRS during the two weeks monitoring period. These results demonstrated that minocycline could mitigate SE-induced brain inflammation and might exert disease-modifying effects in an animal model of temporal lobe epilepsy. These findings offer new insights into deciphering the molecular mechanisms of epileptogenesis and exploring a novel therapeutic strategy for prevention of epilepsy. PMID:25541249

  7. Evidence for Status Epilepticus and Pro-Inflammatory Changes after Intranasal Kainic Acid Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Mounira Sabilallah

    Full Text Available Kainic acid (KA is routinely used to elicit status epilepticus (SE and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantified for each animal and confirmed by power spectrum analysis. Immunohistochemistry and qPCR were performed to define brain inflammation occurring after SE, including activated microglial phenotypes. Long term video-EEG recording was also performed. Titration of IN KA showed that a dose of 30 mg/kg was associated with low mortality while eliciting SE. IN KA provoked at least one behavioral and electrographic SE in the majority of the mice (>90%. Behavioral and EEG SE were accompanied by a rapid and persistent microglial-astrocytic cell activation and hippocampal neurodegeneration. Specifically, microglial modifications involved both pro- (M1 and anti-inflammatory (M2 genes. Our initial long-term video-EEG exploration conducted using a small cohort of mice indicated the appearance of spike activity or SE. Our study demonstrated that induction of SE is attainable using IN KA in mice. Typical pro-inflammatory brain changes were observed in this model after SE, supporting disease pathophysiology. Our results are in favor of the further development of IN KA as a means to study seizure disorders. A possibility for tailoring this model to drug testing or to study mechanisms of disease is offered.

  8. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

    Energy Technology Data Exchange (ETDEWEB)

    Aellen, Jerome; Kottke, Raimund; Springer, Elisabeth; Weisstanner, Christian; El-Koussy, Marwan; Schroth, Gerhard; Wiest, Roland; Gralla, Jan; Verma, Rajeev K. [University of Bern, University Institute for Diagnostic and Interventional Neuroradiology, University Hospital Bern and Inselspital, Bern (Switzerland); Abela, Eugenio; Schindler, Kaspar [University of Bern, Department of Neurology, Inselspital, Bern (Switzerland); Buerki, Sarah E. [Inselspital, Department of Neuropaediatrics, University Children' s Hospital, Bern (Switzerland)

    2014-11-15

    To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. (orig.)

  9. Propofol effectively inhibits lithium-pilocarpine-induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

    Institute of Scientific and Technical Information of China (English)

    Henglin Wang; Zhuoqiang Wang; Weidong Mi; Cong Zhao; Yanqin Liu; Yongan Wang; Haipeng Sun

    2012-01-01

    Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine. The inhibitory ef-fects of propofol on status epilepticus in rats were judged based on observation of behavior, elec-troencephalography and 24-hour survival rate. Propofol (12.5-100 mg/kg) improved status epilep-ticus in a dose-dependent manner, and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection. Western blot results showed that, 24 hours after induction of status epilepticus, the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly in-creased in rat cerebral cortex and hippocampus. Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels, but not the increase in N-methyl-D-aspartate receptor 2A subunit levels. The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine. This effect may be associated with down-regulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.

  10. Adult tonic-clonic convulsive status epilepticus over the last 11 years in a resource-poor country: a tertiary referral centre study from southern Thailand.

    Science.gov (United States)

    Phabphal, Kanitpong; Geater, Alan; Limapichart, Kitti; Sathirapanya, Pornchai; Setthawatcharawanich, Suwanna

    2013-09-01

    Status epilepticus is a common condition in patients admitted to hospital in resource-poor countries and reports indicate that aetiology, factors of poor outcome, and treatment strategies are variable. To date, there is no report of a prospective study in Thai adults. Herein, we investigated the aetiology, clinical features, factors of predicted poor outcome, and treatment strategies in Thai adult patients who presented with convulsive status epilepticus. A total of 180 patients, whose ages ranged from 15 to 106 years, were included. Of these, 121 patients (67.2%) had acute symptomatic aetiology. The most common aetiology of status epilepticus was encephalitis (36.1%), followed by scarring of the cerebral hemisphere (15%). The median duration of status epilepticus before treatment was three hours. The rate of mortality in the study was 26.7%. Poor outcome was identified in 112 (62.2%) patients. For referral patients, all received only intravenous drugs before referral. The variables that correlated with poor outcome were aetiology and duration of status epilepticus. An approach to incorporate improved prevention of encephalitis, a more effective transportation system, and provision of the essential intravenous antiepileptic drugs would effectively increase the response to treatment.

  11. Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Manoj K.; Sinha, Sanjib [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India); Ravishankar, Shivshankar; Shivshankar, Jai Jai [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

    2009-03-15

    Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 {+-} 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 {+-} 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

  12. Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

    International Nuclear Information System (INIS)

    Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 ± 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 ± 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

  13. Rapid Diagnosis of Nonconvulsive Status Epilepticus Using Reduced-Lead Electroencephalography

    Directory of Open Access Journals (Sweden)

    Brenner, Jay M.

    2015-05-01

    Full Text Available Introduction: Electroencephalography (EEG is indicated for diagnosing nonconvulsive status epilepticus (NCSE in a patient who has altered level of consciousness after a motor seizure. A study in a neonatal population found 94% sensitivity and 78% specificity for detection of seizure using a single-lead device. This study aims to show that a reduced montage EEG would detect 90% of seizures detected on standard EEG. Methods: A portable Brainmaster EEG device was available in the emergency department (ED at all times. Patients presenting to the ED with altered mental status and known history of seizure or a witnessed seizure having a standard EEG were eligible for this study. The emergency physician obtained informed consent from the legally authorized representative (LAR, while an ED technician attached the electrodes to the patient, and a research associate attached the electrodes to the wiring routing to the portable EEG module. A board-certified epileptologist interpreted the tracings via the Internet. Simultaneously, the emergency physician ordered a standard 23-lead EEG, which would be interpreted by the neurologist on call to read EEGs. We compared the epileptologist’s interpretation of the reduced montage EEG to the results of the 23-lead EEG, which was considered the gold standard for detecting seizures. Results: Twelve of 12 patients or 100% had the same findings on reduced-montage EEG as standard EEG. One of 12 patients or 8% had nonconvulsive seizure activity. Conclusion: The results are consistent with prior studies which have shown that 8-48% of patients who have had a motor seizure continue to have nonconvulsive seizure activity on EEG. This study suggests that a bedside reduced-montage EEG can be used to make the diagnosis of NCSE in the ED. Further study will be conducted to see if this technology can be applied to the inpatient neurological intensive care unit setting. [West J Emerg Med. 2015;16(3:442–446.

  14. 非惊厥性癫癎持续状态22例临床分析%Nonconvulsive status epilepticus: clinical analysis of 22 cases

    Institute of Scientific and Technical Information of China (English)

    陈进庆

    2009-01-01

    @@ 癫癎持续状态(status epilepticus,SE)是儿科最常见的急症之一,根据临床发作的形式分为惊厥性(convulsive status epilepticus,CSE)和非惊厥性持续状态(nonconvulsive status epilepticus,NCSE),尽管NCSE对生命威胁较小,但容易被误诊,且能引起认知功能障碍,日益受重视.本研究收集我院2003年3月至2008年12月22例NCSE患儿临床资料,现报道如下.

  15. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dhote, Franck, E-mail: franck.dhote@irba.fr [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Carpentier, Pierre; Barbier, Laure [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Peinnequin, André [Département Effets biologiques des rayonnements, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); and others

    2012-03-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  16. Protective effects of endoplasmic reticulum stress preconditioning on hippocampal neurons in rats with status epilepticus

    Directory of Open Access Journals (Sweden)

    Yi ZHANG

    2014-12-01

    Full Text Available Objective To evaluate the protective effects of endoplasmic reticulum stress preconditioning induced by 2-deoxyglucose (2-DG on hippocampal neurons of rats with status epilepticus (SE and the possible mechanism.  Methods Ninety Sprague-Dawley (SD rats were randomly enrolled into preconditioning group (N = 30, SE group (N = 30 and control group (N = 30. Each group was divided into 6 subsets (N = 5 according to six time points (before seizure, 6 h, 12 h, 1 d, 2 d and 7 d after seizure. The preconditioning group was administered 2-DG intraperitoneally with a dose of 150 mg/kg for 7 days, and the lithium-pilocarpine induced SE rat model was established on both preconditioning group and SE group. The rats were sacrificed at the above six time points, and the brains were removed to make paraffin sections. Nissl staining was performed by toluidine blue to evaluate the hippocampal neuronal damage after seizure, and the number of survival neurons in hippocampal CA1 and CA3 regions of the rats were counted. Immunohistochemical staining was performed to detect the expressions of glucose regulated protein 78 (GRP78 and X-box binding protein 1 (XBP-1 in hippocampal CA3 region of the rats.  Results The number of survival neurons in preconditioning group was much more than that in SE group at 7 d after seizure (t = 5.353, P = 0.000, and was more obvious in CA1 region. There was no significant hippocampal neuronal damage in control group. The expressions of GRP78 and XBP-1 in CA3 region of hippocampus in SE group at 6 h after seizure were significantly higher than that in control group (P = 0.000, and then kept increasing until reaching the peak at 2 d (P = 0.000, for all. The expressions of GRP78 and XBP-1 in hippocampal CA3 region in preconditioning group were significantly higher than that in control group before seizure (P = 0.000, for all. The level of GRP78 maintained the highest at 24 h and 2 d after seizure (P = 0.000, for all, while the XBP-1 level

  17. Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats.

    Science.gov (United States)

    Suchomelova, L; Lopez-Meraz, M L; Niquet, J; Kubova, H; Wasterlain, C G

    2015-10-01

    This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae. PMID:26259902

  18. Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats.

    Science.gov (United States)

    Gama, Iclea Rocha; Trindade-Filho, Euclides Marinho; Oliveira, Suzana Lima; Bueno, Nassib Bezerra; Melo, Isabelle Tenório; Cabral-Junior, Cyro Rego; Barros, Elenita M; Galvão, Jaqueline A; Pereira, Wanessa S; Ferreira, Raphaela C; Domingos, Bruna R; da Rocha Ataide, Terezinha

    2015-02-01

    Two sources of medium-chain triglycerides--triheptanoin with anaplerotic properties and coconut oil with antioxidant features--have emerged as promising therapeutic options for the management of pharmacoresistant epilepsy. We investigated the effects of ketogenic diets (KDs) containing coconut oil, triheptanoin, or soybean oil on pilocarpine-induced status epilepticus (SE) in rats. Twenty-four adult male Wistar rats were divided into 4 groups and fed a control diet (7% lipids) or a KD containing soybean oil, coconut oil, or triheptanoin (69.8% lipids). The ketogenic and control diets had a lipid:carbohydrate + protein ratio of 1:11.8 and 3.5:1, respectively. SE was induced in all rats 20 days after initiation of the dietary treatment, through the administration of pilocarpine (340 mg/kg; i.p.). The latency, frequency, duration, and severity of seizures before and during SE were observed with a camcorder. SE was aborted after 3 h with the application of diazepam (5 mg/kg; i.p.). The rats in the triheptanoin-based KD group needed to undergo a higher number of seizures to develop SE, as compared to the control group (P < 0.05). Total weight gain, intake, energy intake, and feed efficiency coefficient, prior to induction of SE, differed between groups (P < 0.05), where the triheptanoin-based KD group showed less weight gain than all other groups, less energy intake than the Control group and intermediate values of feed efficiency coefficient between Control and other KDs groups. Triheptanoin-based KD may have a neuroprotective effect on the establishment of SE in Wistar rats.

  19. [Acute edematous encephalopathy presenting with refractory generalized status epilepticus: an autopsy case].

    Science.gov (United States)

    Yamashita, M; Yamamoto, T; Yasuda, T

    2001-11-01

    A previously healthy, 29-year-old man developed generalized convulsion with disturbed consciousness 3 days after the flu-like symptoms. On the next day, his convulsion evolved into generalized status epilepticus (GSE) that was unresponsive to administration of various anticonvulsants. Then, intravenous anesthetic agents, including midazolam, propofol and vecuronium sodium, were continuously infused. During the following 9 days, despite of high-dose infusion of these anesthetic agents, his GSE could not be suppressed, and complex partial seizure with secondary generalization frequently occurred. The patient was comatose and mechanically ventilated, whereas the brainstem reflexes were preserved. Electroencephalogram revealed a diffuse slowing of the background activity and occasional focal spike and wave complexes with secondary generalization. Cerebrospinal fluid analysis showed pleocytosis and elevated protein concentration. Cranial CT scans obtained on day 8 demonstrated brain edema. On day 10, his GSE ceased with abolition of the brainstem reflexes, and he lapsed into brain death resulting from the progressive brain edema. Over the following six days, his systemic circulation gradually worsened, and he died on day 16. On postmortem examination, the brain was markedly edematous and showed the findings consistent with acute anoxic encephalopathy with extensive circulatory stasis. Mild gliosis was observed in the insular cortex, yet no evidence of inflammatory disease was found throughout the brain. This patient was characterized by acutely progressive severe brain edema without inflammatory changes, suggesting that his primary disease was acute toxic encephalopathy presumably induced by viral infection. His GSE was refractory and unresponsive to the intensive treatment with the intravenous anesthetic agents. This case epitomizes the difficulties in controlling refractory seizures in some patients with encephalopathy or encephalitis.

  20. Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline

    Science.gov (United States)

    Pandit, Awadh Kishor; Ihtisham, Kavish; Garg, Ajay; Gulati, Sheffali; Padma, Madakasira Vasantha; Tripathi, Manjari

    2013-01-01

    Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor's information) were noted. Results: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis. PMID:24339583

  1. Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline

    Directory of Open Access Journals (Sweden)

    Awadh Kishor Pandit

    2013-01-01

    Full Text Available Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE, epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI, cerebrospinal-fluid analysis (CSF, and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor′s information were noted. Results: There were 15 (males = 10 patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years. The most common onset was subacute (64% and four (29% patients presented as SE. Predominant clinical presentations were seizures (100% almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40% it was normal, six (40% showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%, voltage-gated potassium channel antibody in five (36%, two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67% cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis.

  2. Persistent reduction of hippocampal glutamine synthetase expression after status epilepticus in immature rats.

    Science.gov (United States)

    van der Hel, W Saskia; Hessel, Ellen V S; Bos, Ineke W M; Mulder, Sandra D; Verlinde, Suzanne A M W; van Eijsden, Pieter; de Graan, Pierre N E

    2014-12-01

    Mesiotemporal sclerosis (MTS), the most frequent form of drug-resistant temporal lobe epilepsy, often develops after an initial precipitating injury affecting the immature brain. To analyse early processes in epileptogenesis we used the juvenile pilocarpine model to study status epilepticus (SE)-induced changes in expression of key components in the glutamate-glutamine cycle, known to be affected in MTS patients. SE was induced by Li(+) /pilocarpine injection in 21-day-old rats. At 2-19 weeks after SE hippocampal protein expression was analysed by immunohistochemistry and neuron damage by FluoroJade staining. Spontaneous seizures occurred in at least 44% of animals 15-18 weeks after SE. As expected in this model, we did not observe loss of principal hippocampal neurons. Neuron damage was most pronounced in the hilus, where we also detected progressive loss of parvalbumin-positive GABAergic interneurons. Hilar neuron loss (or end-folium sclerosis), a common feature in patients with MTS, was accompanied by a progressively decreased glutamine synthetase (GS)-immunoreactivity from 2 (-15%) to 19 weeks (-33.5%) after SE. Immunoreactivity for excitatory amino-acid transporters, vesicular glutamate transporter 1 and glial fibrillary acidic protein was unaffected. Our data show that SE elicited in 21-day-old rats induces a progressive reduction in hilar GS expression without affecting other key components of the glutamate-glutamine cycle. Reduced expression of glial enzyme GS was first detected 2 weeks after SE, and thus clearly before spontaneous recurrent seizures occurred. These results support the hypothesis that reduced GS expression is an early event in the development of hippocampal sclerosis in MTS patients and emphasize the importance of astrocytes in early epileptogenesis.

  3. Silencing Status Epilepticus-Induced BDNF Expression with Herpes Simplex Virus Type-1 Based Amplicon Vectors.

    Directory of Open Access Journals (Sweden)

    Chiara Falcicchia

    Full Text Available Brain-derived neurotrophic factor (BDNF has been found to produce pro- but also anti-epileptic effects. Thus, its validity as a therapeutic target must be verified using advanced tools designed to block or to enhance its signal. The aim of this study was to develop tools to silence the BDNF signal. We generated Herpes simplex virus type 1 (HSV-1 derived amplicon vectors, i.e. viral particles containing a genome of 152 kb constituted of concatameric repetitions of an expression cassette, enabling the expression of the gene of interest in multiple copies. HSV-1 based amplicon vectors are non-pathogenic and have been successfully employed in the past for gene delivery into the brain of living animals. Therefore, amplicon vectors should represent a logical choice for expressing a silencing cassette, which, in multiple copies, is expected to lead to an efficient knock-down of the target gene expression. Here, we employed two amplicon-based BDNF silencing strategies. The first, antisense, has been chosen to target and degrade the cytoplasmic mRNA pool of BDNF, whereas the second, based on the convergent transcription technology, has been chosen to repress transcription at the BDNF gene. Both these amplicon vectors proved to be effective in down-regulating BDNF expression in vitro, in BDNF-expressing mesoangioblast cells. However, only the antisense strategy was effective in vivo, after inoculation in the hippocampus in a model of status epilepticus in which BDNF mRNA levels are strongly increased. Interestingly, the knocking down of BDNF levels induced with BDNF-antisense was sufficient to produce significant behavioral effects, in spite of the fact that it was produced only in a part of a single hippocampus. In conclusion, this study demonstrates a reliable effect of amplicon vectors in knocking down gene expression in vitro and in vivo. Therefore, this approach may find broad applications in neurobiological studies.

  4. The efficacy of topiramate in adult refractory status epilepticus: experience of a tertiary care center.

    Science.gov (United States)

    Synowiec, Andrea S; Yandora, Kristin A; Yenugadhati, Vamsi; Valeriano, James P; Schramke, Carol J; Kelly, Kevin M

    2012-02-01

    Refractory status epilepticus (RSE) occurs in patients with SE when they fail to respond to traditional medical therapy. Because there are very few case reports of topiramate (TPM) treatment of RSE in adult patients, we examined our experience with TPM with regard to its safety and efficacy in seizure termination in RSE in an adult patient population. We report a retrospective review of 35 adult patients with RSE who were treated with TPM in addition to other antiepileptic drugs (AEDs) between 2003 and 2010. After failure of initial treatments of benzodiazepines and weight-based intravenous loading doses of standard AEDs, TPM tablets were crushed and administered via nasogastric tube. Data were collected on age, gender, history of epilepsy, etiology of RSE, daily dose of TPM, co-therapeutic agents, treatment response, and disposition. Following initiation of TPM use and discontinuation of continuous intravenous anesthetics with no additional AEDs administered, cumulative cessation of RSE in patients was 4/35 (11%) at one day, 10/35 (29%) at two days, and 14/35 (40%) at three days. However, when including all patients and comparing the two patient groups in which RSE was or was not terminated within three days of initiating TPM as the last or not last AED given, there was no significant difference. Time to TPM response was not associated with the type of seizures, etiology of SE, or whether there was a history of epilepsy. There were no documented side effects or complications of therapy with TPM. This study provides support for the use of TPM as an adjunctive agent in the treatment of RSE.

  5. Silencing Status Epilepticus-Induced BDNF Expression with Herpes Simplex Virus Type-1 Based Amplicon Vectors.

    Science.gov (United States)

    Falcicchia, Chiara; Trempat, Pascal; Binaschi, Anna; Perrier-Biollay, Coline; Roncon, Paolo; Soukupova, Marie; Berthommé, Hervé; Simonato, Michele

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) has been found to produce pro- but also anti-epileptic effects. Thus, its validity as a therapeutic target must be verified using advanced tools designed to block or to enhance its signal. The aim of this study was to develop tools to silence the BDNF signal. We generated Herpes simplex virus type 1 (HSV-1) derived amplicon vectors, i.e. viral particles containing a genome of 152 kb constituted of concatameric repetitions of an expression cassette, enabling the expression of the gene of interest in multiple copies. HSV-1 based amplicon vectors are non-pathogenic and have been successfully employed in the past for gene delivery into the brain of living animals. Therefore, amplicon vectors should represent a logical choice for expressing a silencing cassette, which, in multiple copies, is expected to lead to an efficient knock-down of the target gene expression. Here, we employed two amplicon-based BDNF silencing strategies. The first, antisense, has been chosen to target and degrade the cytoplasmic mRNA pool of BDNF, whereas the second, based on the convergent transcription technology, has been chosen to repress transcription at the BDNF gene. Both these amplicon vectors proved to be effective in down-regulating BDNF expression in vitro, in BDNF-expressing mesoangioblast cells. However, only the antisense strategy was effective in vivo, after inoculation in the hippocampus in a model of status epilepticus in which BDNF mRNA levels are strongly increased. Interestingly, the knocking down of BDNF levels induced with BDNF-antisense was sufficient to produce significant behavioral effects, in spite of the fact that it was produced only in a part of a single hippocampus. In conclusion, this study demonstrates a reliable effect of amplicon vectors in knocking down gene expression in vitro and in vivo. Therefore, this approach may find broad applications in neurobiological studies.

  6. Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children.

    Science.gov (United States)

    Buttram, Sandra D W; Au, Alicia K; Koch, Joshua; Lidsky, Karen; McBain, Kristin; O'Brien, Nicole; Zielinski, Brandon A; Bell, Michael J

    2015-12-01

    Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a

  7. Non-convulsive status epilepticus after ischemic stroke: a hospital-based stroke cohort study.

    Science.gov (United States)

    Belcastro, Vincenzo; Vidale, Simone; Gorgone, Gaetano; Pisani, Laura Rosa; Sironi, Luigi; Arnaboldi, Marco; Pisani, Francesco

    2014-11-01

    To evaluate in the setting of a stroke unit ward the usefulness of a prolonged (>6 h) video-EEG recording (PVEEG) in identifying non-convulsive status epilepticus (NCSE) in patients with an acute ischemic stroke. Predictors of NCSE were also evaluated. Patients with an acute ischemic stroke, referred to our unit, were included in this prospective observational study. A PVEEG recording was implemented after stroke in all patients during the first week: (a) promptly in those exhibiting a clear or suspected epileptic manifestation; (b) at any time during the routine activity in the remaining patients. After the first week, a standard EEG/PVEEG recording was hooked up only in presence of an evident or suspected epileptic manifestation or as control of a previous epileptic episode. NCSE was identified in 32 of the 889 patients (3.6 %) included in the study. It occurred early (within the first week) in 20/32 (62.5 %) patients and late in the remaining 12. Diagnosis was made on the basis of a specific clinical suspect (n = 19, 59.4 %) or without any suspect (n = 13, 40.6 %). In a multivariate analysis, a significant association of NCSE was observed with NIHSS score, infarct size and large atherothrombotic etiology. NCSE is not a rare event after an acute ischemic stroke and a delayed diagnosis could worsen patient prognosis. Since NCSE can be difficult to be diagnosed only on clinical grounds, implementation of a prompt PVEEG should be kept available in a stroke unit whenever a patient develop signs, although subtle, consistent with NCSE.

  8. Beneficial influence of physical exercise following status epilepticus in the immature brain of rats.

    Science.gov (United States)

    Gomes, F G Novaes; Gomes Da Silva, S; Cavalheiro, E A; Arida, R M

    2014-08-22

    Studies in adult animals have demonstrated a beneficial effect of physical exercise on epileptic insults. Although the effects of physical exercise on the mature nervous system are well documented, its influence on the developing nervous system subjected to injuries in childhood has been little explored. The purpose of our study was to investigate whether a physical exercise program applied during brain development could influence the hippocampal plasticity of rats submitted to status epilepticus (SE) induced by pilocarpine model at two different ages of the postnatal period. Male Wistar rats aged 18 (P18) and 28 (P28) days were randomly divided into four groups: Control (CTRL), Exercise (EX), SE (SE) and SE Exercise (SE/EX) (n=17 per group). After the aerobic exercise program, histological and behavioral (water maze) analyses were performed. Our results showed that only animals subjected to pilocarpine-induced SE at P28 presented spontaneous seizures during the observational period. A significant reduction in seizure frequency was observed in the SE/EX group compared to the SE group. In adulthood, animals submitted to early-life SE displayed impairment in long-term memory in the water maze task, while the exercise program reversed this deficit. Reduced mossy fiber sprouting in the dentate gyrus was noted in animals that presented spontaneous seizures (SE/EX vs SE). Exercise increased cell proliferation (Ki-67 staining) and anti-apoptotic response (bcl-2 staining) and reduced pro-apoptotic response (Bax staining) in animals of both ages of SE induction (P18/28). Exercise also modified the brain-derived neurotrophic factor (BDNF) levels in EX and SE/EX animals. Our findings indicate that in animals subjected to SE in the postnatal period a physical exercise program brings about beneficial effects on seizure frequency and hippocampal plasticity in later stages of life. PMID:24857853

  9. Anti-NMDA-R encephalitis: Should we consider extreme delta brush as electrical status epilepticus?

    Science.gov (United States)

    Chanson, Eve; Bicilli, Élodie; Lauxerois, Michel; Kauffmann, Sophie; Chabanne, Russell; Ducray, François; Honnorat, Jérome; Clavelou, Pierre; Rosenberg, Sarah

    2016-02-01

    Seizures are common clinical manifestations in anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis, among other neurological and psychiatric symptoms. During the course of the disease, some specific EEG patterns have been described: generalized rhythmic delta activity (GRDA) and extreme delta brush (EDB). In comatose patients, the association of these EEG abnormalities with subtle motor manifestations can suggest ongoing non-convulsive status epilepticus (NCSE). We report the case of a 28-year-old woman admitted for a clinical presentation typical of anti-NMDA-R encephalitis, which was confirmed by CSF analysis. She was rapidly intubated because of severe dysautonomia and disturbed consciousness. Clinical examination revealed subtle paroxysmal and intermittent myoclonic and tonic movements, correlated on video-EEG with GRDA and/or EDB. NCSE was then suspected, but electroclinical manifestations persisted despite many anti-epileptic drugs combinations, or reappeared when barbiturate anesthesia was decreased. In order to confirm or dismiss the diagnosis, intracranial pressure (ICP) and surface video-EEG monitoring were performed simultaneously and revealed no ICP increase, thus being strongly against a diagnosis of seizures. Sedation was progressively weaned, and clinical condition as well as EEG appearance progressively improved. Literature review revealed 11 similar cases, including 2 with focal NCSE. Of the nine other cases, NCSE diagnosis was finally excluded in 5 cases. NCSE diagnosis in association with anti-NMDA-R encephalitis is sometimes very difficult and its occurrence might be overestimated. Video-EEG is highly recommended and more invasive techniques may sometimes be necessary. PMID:26922283

  10. Clinical Significance of Human Metapneumovirus in Refractory Status Epilepticus and Encephalitis: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Aysel Vehapoglu

    2015-01-01

    Full Text Available Encephalitis is a complex neurological disease that is associated with significant morbidity and mortality, and the etiology of the disease is often not identified. Human metapneumovirus (hMPV is a common cause of upper and lower respiratory tract infections in children. Few reports are available showing possible involvement of hMPV in development of neurologic complications. Here, we describe an infant, the youngest case in literature, with refractory status epilepticus and severe encephalitis in whom hMPV was detected in respiratory samples and review diagnostic workup of patient with encephalitis.

  11. Sensorineural hearing loss and status epilepticus associated with ulcerative colitis: Is there enough evidence to support immune-related mechanisms?

    Directory of Open Access Journals (Sweden)

    Sinem Yazici

    2015-01-01

    Full Text Available Ulcerative colitis (UC is characterized by an inflammatory disorder of the gastrointestinal tract. Immune-mediated extraintestinal manifestations of UC have increasingly attracted attention in the literature recently, for which UC is now considered as a systemic disease. Neurologic involvement associated with UC is probably under-reported because of the unawareness of many physicians, although early recognition and treatment are crucial in preventing major morbidity and sequel. In this case report is presented a patient newly diagnosed as UC, who developed both sensorineural hearing loss and intractable status epilepticus that we suggest to have resulted from immune-mediated mechanisms.

  12. The effect of STAT3 Inhibition on status epilepticus and subsequent spontaneous seizures in the Pilocarpine Model of Acquired Epilepsy

    OpenAIRE

    Grabenstatter, H. L.; Angel, Y. Cruz Del; Carlsen, J.; Wempe, M. F.; White, A. M.; Cogswell, M.; Russek, S. J.; BROOKS-KAYAL, A. R.

    2013-01-01

    Pilocarpine-induced status epilepticus (SE), which results in temporal lobe epilepsy (TLE) in rodents, activates the JAK/STAT pathway. In the current study, we evaluate whether brief exposure to a selective inhibitor of the JAK/STAT pathway (WP1066) early after the onset of SE effects the severity of SE or reduces later spontaneous seizure frequency via inhibition of STAT3-regulated gene transcription. Rats that received systemic WP1066 or vehicle at the onset of SE were continuously video-EE...

  13. Status epilepticus of patient care and nutrition%癫痫持续状态患者的护理与营养浅析

    Institute of Scientific and Technical Information of China (English)

    齐敬英; 齐敬东

    2015-01-01

    Status epilepticus by a variety of causes a chronic brain disease. In addition to conventional medical treatment, nursing science, reasonable diet, can effectively delay the number of episodes of status epilepticus, play the role of adjuvant therapy.%癫痫持续状态是由多种原因导致的一种脑部慢性疾病。除常规药物治疗外,科学的护理、合理的膳食,能有效延缓癫痫持续状态的发作次数,起到辅助治疗的作用。

  14. A rare case of neonatal sepsis/meningitis caused by Pasteurella multocida complicated with status epilepticus and focal cerebritis.

    Science.gov (United States)

    Spadafora, R; Pomero, G; Delogu, A; Gozzoli, L; Gancia, P

    2011-01-01

    Pasteurella multocida is normally present in respiratory and digestive tract of many domestic and wild animals, but is a rare pathogen in neonatal infection. Here we describe for the first time a case of meningitis complicated by status epilepticus and right parietal lobe cerebritis. The patient showed a dramatic clinical onset characterized by septic appearance and prolonged seizures. Multidrug anticonvulsivant therapy was used to control the status epilepticus, but despite the aggressive treatment electrical crises were still evident 24 hours after the admission. Furthermore, a brain MRI, performed to investigate a persistent intermittent fever even if CSF became sterile, showed a focus cerebritis in the right parietal lobe, early stage of the cerebral abscess. Prolonged antibiotic therapy with steroids was requested to solve the cerebritis area. Interestingly, direct contact between the patient and domestic animals was denied by the family, but the father reported a contact with a rooster, killed and cooked few days before, suggesting, as previously described, that Pasteurella may also be transmitted through asymptomatic human carrier. The patient had a favourable outcome with no medium-term sequelae one month after discharge, but the severity of the clinical course and the unpredictable way of transmission highlight the importance of hygiene measures approaching infants. PMID:22423481

  15. Diagnosis and Treatment of Status Epilepticus%癫痫持续状态的诊断与治疗

    Institute of Scientific and Technical Information of China (English)

    何文娟; 谢辉

    2013-01-01

    Status epilepticus is a pathological state, which is characterized by repeated or sustained seizure. It is one of the common life-threatening medical emergencies, requiring urgent disposal. Timely and accurate diagnosis, adopt correct therapeutic measure and reasonable use antiepileptic drugs may effectively terminate the seizure as soon as possible, prevent recurrence and complications, and reduce mortality and disability. In this review we summarize the diagnosis and treatment of status epilepticus.%  癫痫持续状态是一种以反复或持续的癫痫发作为特征的病理状况,是常见的威胁生命的医学急症之一,需紧急处置。临床医师及时准确的诊断,正确治疗措施的采取,以及抗癫痫药物的合理使用可以尽快、尽早、有效地终止发作,预防复发及并发症,降低致死、致残率。本文就癫痫持续状态的诊断及治疗进行综述。

  16. Region-specific vulnerability to endoplasmic reticulum stress-induced neuronal death in rat brain after status epilepticus

    Indian Academy of Sciences (India)

    Jing Chen; Hu Guo; Guo Zheng; Zhong-Nan Shi

    2013-12-01

    We sought to clarify the involvement and the intra-cerebral distribution variability of C/EBP homologous protein (CHOP), a representative molecule related to endoplasmic reticulum (ER) stress-induced cell death signalling pathways, in neuronal death resulting from status epilepticus in rats. The expression patterns of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double-fluorescent staining of CHOP and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labelling (TUNEL) method were performed to clarify the involvement of CHOP in cell death. SE resulted in a time-dependent increase in the expression of GRP78 and CHOP. The expression of GRP78 protein was increased at 3, 6 and 12 h after SE and no brain region variability was found. The expression of CHOP protein was also increased, reached its peak at 24 h and remained high at 48 h. CHOP protein expression, however, showed brain region variability with highest expression noted in the hippocampus followed by the striatum, and lowest in the cortex. The up-regulation of CHOP occurring at the transcriptional level was demonstrated by real-time PCR. Double fluorescence showed that CHOP expression strongly correlated with neurons undergoing apoptosis. The results indicated that SE compromises the function of the ER and that the hippocampus is more vulnerable than the cortex and the striatum.

  17. Gabapentin administration reduces reactive gliosis and neurodegeneration after pilocarpine-induced status epilepticus.

    Directory of Open Access Journals (Sweden)

    Alicia Raquel Rossi

    Full Text Available The lithium-pilocarpine model of epilepsy reproduces in rodents several features of human temporal lobe epilepsy, by inducing an acute status epilepticus (SE followed by a latency period. It has been proposed that the neuronal network reorganization that occurs during latency determines the subsequent appearance of spontaneous recurrent seizures. The aim of this study was to evaluate neuronal and glial responses during the latency period that follows SE. Given the potential role of astrocytes in the post-SE network reorganization, through the secretion of synaptogenic molecules such as thrombospondins, we also studied the effect of treatment with the α2δ1 thrombospondin receptor antagonist gabapentin. Adult male Wistar rats received 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once SE was achieved, seizures were stopped with 20 mg/kg diazepam. Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days. In vitro experiments were performed in dissociated mixed hippocampal cell culture exposed to glutamate, and subsequently treated with gabapentin or vehicle. During the latency period, the hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis, with increased GFAP and nestin expression. Gliosis intensity was dependent on the Racine stage attained by the animals and peaked 15 days after SE. Microglia was also reactive after SE, and followed the same pattern. Neuronal degeneration was present in SE-animals, and also depended on the Racine stage and the SE duration. Polysialic-acid NCAM (PSA-NCAM expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals. Gabapentin treatment was able to reduce reactive gliosis, decrease neuronal loss and normalize PSA-NCAM staining in hippocampal CA-1. In vitro, gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity. Our results show that gabapentin treatment during the

  18. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  19. 癫痫持续状态的急救与护理探讨%The Methods of Emergency and Nursing in Patients with Status Epilepticus

    Institute of Scientific and Technical Information of China (English)

    黄妙娟

    2012-01-01

      目的:探讨癫痫持续状态的有效急救和护理方法。方法:选取31例癫痫持续状态患者,对患者采取积极的急救及综合护理,观察救治效果。结果:31例癫痫持续状态患者经积极治疗,25例患者无再发癫痫,6例患者再发2~5次,无患者死亡。结论:对癫痫持续状态患者采取有效的急救及护理,可有效减少癫痫发作次数,改善患者预后。%  Objective:To explore effective methods of first-aid and nursing for patients with status epilepticus.Method:Select 31 patients with status epilepticus,take an active first aid and nursing,observation effective.Result:In 31 patients with status epilepticus,25 patients have not attack epilepsy once again,6 cases have attack epilepsy 2 to 5 times once again,no patient died.Conclusion:To patients with status epilepticus,take effective first aid and nursing,can effectively reduce the attack times and improving the prognosis.

  20. Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: A case series, characterisation of the antigen, and analysis of the effects of antibodies

    NARCIS (Netherlands)

    M. Petit-Pedrol (Mar); T. Armangue (Thaís); X. Peng (Xiaoyu); L. Bataller (Luis); T. Cellucci (Tania); R. Davis (Rebecca); L. McCracken (Lindsey); E. Martinez-Hernandez (Eugenia); W.P. Mason (Warren); M.C. Kruer (Michael); D.G. Ritacco (David); W. Grisold (Wolfgang); M.J. Meaney; C. Alcalá (Carmen); P.A.E. Sillevis Smitt (Peter); M.J. Titulaer (Maarten); R. Balice-Gordon (Rita); F. Graus (Francesc); J. Dalmau (Josep)

    2014-01-01

    textabstractBackground: Increasing evidence suggests that seizures and status epilepticus can be immune-mediated. We aimed to describe the clinical features of a new epileptic disorder, and to establish the target antigen and the effects of patients' antibodies on neuronal cultures. Methods: In this

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

    Directory of Open Access Journals (Sweden)

    Rocco Galimi

    2011-03-01

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

  2. Efficacy and safety of non-intravenous midazolam for the treatment of status epilepticus in children: a Meta-analysis

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    Yan LIN

    2016-02-01

    Full Text Available Objective To evaluate the clinical efficacy and safety of non-intravenous midazolam for treating status epilepticus (SE in children.  Methods Taking midazolam, status epilepticus and children both in Chinese and English as search terms, retrieve in databases such as PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI, VIP and Wanfang Data, assisted by manual searching and Google Scholar, in order to collect randomized controlled trials (RCTs about non-intravenous midazolam for treating SE in children from January 2000 to January 2015. Jadad Scale was used to evaluate the quality of literatures. Meta-analysis was performed by using RevMan 5.3 software. Results There were a total of 258 records after preliminary searching, and 6 RCTs involving 766 episodes were finally included after excluding duplicate ones and those which did not meet the inclusion criteria. The results were as follows: 1 midazolam via intranasal administration was as effective as intravenous diazepam in achieving seizure control in children (RD = -0.070, 95%CI: -0.200—0.060, P = 0.290. However, non-intravenous (intranasal or buccal midazolam showed better effects on seizure control than rectal diazepam (RD = 0.170, 95% CI: 0.030—0.320; P = 0.020. 2 The mean time from arrival at hospital to cessation was not significantly different between intranasal midazolam and intravenous diazepam (SMD = -1.570, 95%CI: -3.280—0.140; P = 0.070. 3 There was no statistical difference between intranasal midazolam and intravenous diazepam for the time from giving drug to cessation (SMD = 0.240, 95%CI: -0.110—0.590; P = 0.170. 4 There was no statistical difference on the occurrence rate of adverse drug reactions between non-intravenous midazolam and intravenous or non-intravenous diazepam (RD = -0.010, 95% CI: -0.030—0.200; P = 0.500.  Conclusions Non-intravenous midazolam is safe and effective in the treatment for status epilepticus in children. However, the

  3. Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus – A MRI Study Using Susceptibility Weighted Imaging

    Science.gov (United States)

    Verma, Rajeev Kumar; Abela, Eugenio; Schindler, Kaspar; Krestel, Heinz; Springer, Elisabeth; Huber, Adrian; Weisstanner, Christian; Hauf, Martinus; Gralla, Jan; Wiest, Roland

    2016-01-01

    Objective The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). Methods We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. Results Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. Conclusions SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions. PMID:27486662

  4. The research status quo and prospects of refractory status epilepticus%难治性癫痫持续状态的研究现状与展望

    Institute of Scientific and Technical Information of China (English)

    王晓平; 孙红斌

    2013-01-01

    难治性癫痫持续状态(refractory status epilepticus,RSE)是一种严重的神经科危急重症,有着较高的发病率和死亡率.目前还没有统一的诊治指南.本文就近年来有关RSE的流行病学、病因、诊断、发病机制、药物和非药物处理、预后相关因子分析的研究进展做一简要阐述.

  5. Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Hiroshi Yamaguchi

    2016-01-01

    Full Text Available Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy. Septic encephalopathy (SE is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure.

  6. Simple partial status epilepticus localized by single-photon emission computed tomography subtraction in chronic cerebral paragonimiasis.

    Science.gov (United States)

    Joo, Eun Yeon; Kim, Jee Hyun; Tae, Woo Suk; Han, Sun Jung; Kim, Seunghwan; Kim, Myoung-Hee; Byun, Hong Sik; Hong, Seung Bong

    2004-10-01

    A patient with chronic cerebral paragonimiasis began to have new motor seizures of the right face manifested by clonic contractions that occurred several hundred times a day, consistent with simple partial status epilepticus. Ictal electroencephalogram discharges started from the left frontal region and then spread to the left hemisphere with left frontal maximum. But clinical seizures were limited to the right face. The frequent partial seizures were controlled by the intravenous infusion of phenytoin. Brain magnetic resonance imaging showed multiple conglomerated round nodules with encephalomalacia in the left temporal and occipital lobes. Applying the technique of ictal-interictal single-photo emission computed tomography subtraction, the authors were able to localize the focal ictal-hyperperfusion on left precentral cortex adjacent to the lesions that correspond to the anatomical distribution of left face motor area.

  7. 癫痫持续状态的治疗进展(下)%Status Epilepticus:Update on Treatment

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ 在上一节我们介绍了美国旧金山癫痫持续状态院前治疗的试验研究(Prehospital Treatment of Status Epilepticus Study)、美国退伍军人管理局协作试验(Veterans Administration Cooperative Trial)的一些研究结果以及顽固性癫痫持续状态(RSE)的定义、神经性毒剂和RSE的巴比妥酸盐类和苯二氮革类药物治疗,本节我们将继续介绍RSE的异丙酚(Propofol)治疗和其他一些疗法.

  8. Phase-locking of epileptic spikes to ongoing delta oscillations in non-convulsive status-epilepticus

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    Rikkert eHindriks

    2013-12-01

    Full Text Available The EEG of patients in non-convulsive status epilepticus (NCSE often displays delta oscillations or generalized spike-wave discharges. In some patients, these delta oscillations coexist with intermittent epileptic spikes. In this study we verify the prediction of a computational model of the thalamo-cortical system that these spikes are phase-locked to the delta oscillations. We subsequently describe the physiological mechanism underlying this observation as suggested by the model. It is suggested that the spikes reflect inhibitory stochastic fluctuations in the input to thalamo-cortical relay neurons and phase-locking is a consequence of differential excitability of relay neurons over the delta cycle. Further analysis shows that the observed phase-locking can be regarded as a stochastic precursor of generalized spike-wave discharges. This study thus provides an explanation of intermittent spikes during delta oscillations in NCSE and might be generalized to other encephathologies in which delta activity can be observed.

  9. Diagnosing Sporadic Creutzfeldt-Jakob Disease in a Patient with a Suspected Status Epilepticus in the Intensive Care Unit

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    Harm J. van der Horn

    2013-01-01

    Full Text Available Objective. Several tests are available in the diagnostics of sporadic Creutzfeldt-Jakob disease (sCJD; however, none of these is conclusive. We review the values of these tests, from an intensive care unit (ICU perspective. Methods. Case report and review of the literature. Results. A 53-year-old woman initially presenting with psychiatric symptoms developed myoclonus and was admitted 1 month later to the ICU with a suspected nonconvulsive status epilepticus and respiratory insufficiency, probably due to extensive antiepileptic drug therapy. Typical MRI and EEG findings and a positive 14-3-3 protein led to the diagnosis of sCJD. All treatments were terminated, and autopsy confirmed sCJD. Conclusions. Clinical signs combined with MRI, EEG, and 14-3-3 and/or tau protein determination might be sufficient to diagnose or exclude sCJD and may therefore prevent the application of unnecessary diagnostic tests.

  10. Nonconvulsive Status Epilepticus%癫痫的临床研究进展 第三节非惊厥癫痫持续状态(上)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ 1非惊厥癫痫持续状态的历史 在这里我们有必要追溯一下非惊厥癫痫持续状态(Nonconvulsive Status Epilepticus,NCSE)的历史.癫痫持续状态(Status Epilepticus,SE)最早是在19世纪初以惊厥持续状态的形式被描述的.直到19世纪末,人们才意识到SE可以表现为非惊厥形式,并且这种非惊厥形式最初被描述为类似神游或是胡言乱语的混乱状态.

  11. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

    Science.gov (United States)

    Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram; Bañuelos-Cabrera, Ivette; Magdaleno-Madrigal, Víctor; Fernández-Mas, Rodrigo; Besio, Walter; Rocha, Luisa

    2015-08-01

    The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 μs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (Status Epilepticus".

  12. Clinical analysis of treatment of patients with status epilepticus%癫痫持续状态患者的临床治疗分析

    Institute of Scientific and Technical Information of China (English)

    任建刚

    2011-01-01

    Objective To evaluate the clinical status epilepticus treatment methods and efficacy. Methods A retrospective analysis of clinical data of our hospital in January 2008 - December 2009 in hospital status epilepticus in 50 patients. Results Totally 50 patients after treatment, complete control in 21 cases, effective in 15 cases, 10 cases, efficiency is poor in 3 cases, invalid in 1 patient, the effective rate was 92% ; Children with treatment than adult patients, two groups efficiency, the difference was statistically significant (P < 0. 05). Conclusions Status epilepticus focuses on finding the cause, control of seizures and targeted therapy, timely and effective control of seizures is the key to the rescue of status epilepticus.%目的 探讨对癫痫持续状态的临床用药方法及疗效.方法 回顾性分析2008年1月至2009年12月住院的癫痫持续状态50例患者的临床资料.结果 本组50例患者经治疗,完全控制21例,显效15例,有效10例,效差3例,无效1例,有效率为92%;儿童患者治疗效果优于成人患者,两组有效率比较,差异有统计学意义(P<0.05).结论 癫痫持续状态重在寻找病因、控制发作和有针对性的治疗,及时有效地控制痉挛发作是抢救癫痫持续状态的关键.

  13. 儿童癫(癎)持续状态治疗进展%Progress of treatment for status epilepticus in children

    Institute of Scientific and Technical Information of China (English)

    夏蝉; 单小鸥; 陈其

    2010-01-01

    Status epilepticus(SE)is one of the most common medical emergencies in children.There has been some recent understanding of this fife-threatening condition with reference to the definition,forms of ignorable seizure,drug treatment and role of EEG monitoring.This review discusses the current information regarding the definition,diagnosis,treatment of status epilepticus and the latest advance on management of refractory SE in children.%癫(癎)持续状态(status epilepticus,SE)是小儿时期最常见的危急重症之一.近年来,对于其定义、易忽视的发作形式、药物治疗及脑电图监测的作用不断有新的认识.本文着重对于SE定义、诊断、治疗等方面的新进展进行综述,并介绍国外难治性SE的最新治疗方案.

  14. Evaluation of the efficacy of sodium valproate in convulsive status epilepticus following to ıschemic stroke

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    Hasan Hüseyin Özdemir

    2015-04-01

    Full Text Available Objective : Convulsive status epilepticus (CSE is very rarely observed after ischaemic stroke. Sodium valproate (SV is one of the agents used in the treatment of CSE, but its role still controversial, and its degree of efficacy in treating CSE that develops following stroke is unclear. Method : We evaluated 19 patients who were treated with intravenous (IV SV (20 mg/kg, 2 mg/kg/h-12h after diazepam. Patients’ modified Rankin scores (mRS, SE types, and changes in biochemical parameters after treatment were assessed. Results : CSE was successfully treated in 12 (63.15% patients. Side effects such as hypotension and allergic reactions were observed in two patients. Refractory SE development was observed in 5 (29.4% patients with high mRS (˃ 3. No significant deterioration in patients’ laboratory evaluations, conducted before and after status, was observed. Conclusion : SV may be safe and effective in the treatment of CSE observed after ischaemic stroke, especially in patients with low mRS.

  15. Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

    Science.gov (United States)

    Leclercq, Karine; Kaminski, Rafal M

    2015-08-01

    Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks

  16. Níveis dos neurotransmissores estriatais durante o estado epiléptico Striatal monoamines levels during status epilepticus

    Directory of Open Access Journals (Sweden)

    Rivelilson Mendes de Freitas

    2003-01-01

    Full Text Available O objetivo desse estudo foi verificar os níveis dos neurotransmissores estriatais de ratas adultas durante o estado epiléptico induzido pela pilocarpina. Ratas wistar foram tratadas com uma única dose de pilocarpina (400 mg/kg por via subcutânea (S.C.; P400 e os controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC eletroquímico, no corpo estriado de ratas que no período de observação de 1 hora desencadearam estado epiléptico e que sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido diidroxifenilacético e aumento na concentração do ácido 5-hidroxiindolacético. Nenhuma alteração foi observada no 4-hidroxi-3-metoxi-fenilacético. Os resultados sugerem que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo no corpo estriado de ratos desenvolvidos.The purpose of the present work to investigate the striatal neurotransmissors level in adult rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400 mg/kg; s.c.; P400 and the controls received saline. Adult animals were closed observed for behavioural changes during 1h. In this period, the animals that developed status epilepticus and survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determiden by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid was reduced and an concentration increase in 5-hydroxyindolacetic acid. Didn't observed alteration in 4-hydroxy-3-methoxy-phenylacetic acid. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in rat mature striatum.

  17. A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat

    Science.gov (United States)

    Pérès, Isabelle A. A.; Hadid, Rebecca D.; Amada, Naoki; Hill, Charlotte; Williams, Claire; Stanford, Ian M.; Morris, Christopher M.; Jones, Roland S. G.; Whalley, Benjamin J.; Woodhall, Gavin L.

    2016-01-01

    Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles. PMID:26909803

  18. Morphological alterations in newly born dentate gyrus granule cells that emerge after status epilepticus contribute to make them less excitable.

    Directory of Open Access Journals (Sweden)

    Julián Tejada

    Full Text Available Computer simulations of external current stimulations of dentate gyrus granule cells of rats with Status Epilepticus induced by pilocarpine and control rats were used to evaluate whether morphological differences alone between these cells have an impact on their electrophysiological behavior. The cell models were constructed using morphological information from tridimensional reconstructions with Neurolucida software. To evaluate the effect of morphology differences alone, ion channel conductances, densities and distributions over the dendritic trees of dentate gyrus granule cells were the same for all models. External simulated currents were injected in randomly chosen dendrites belonging to one of three different areas of dentate gyrus granule cell molecular layer: inner molecular layer, medial molecular layer and outer molecular layer. Somatic membrane potentials were recorded to determine firing frequencies and inter-spike intervals. The results show that morphologically altered granule cells from pilocarpine-induced epileptic rats are less excitable than control cells, especially when they are stimulated in the inner molecular layer, which is the target area for mossy fibers that sprout after pilocarpine-induced cell degeneration. This suggests that morphological alterations may act as a protective mechanism to allow dentate gyrus granule cells to cope with the increase of stimulation caused by mossy fiber sprouting.

  19. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.; Braitman, D.J.

    1992-12-31

    The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a post treatment (30, 100 or 300 micron g/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions and electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Post treatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity....Seizure-related brain damage, Organophosphorus compound, Nerve agent, Cholinesterase inhibition, Excitotoxicity, Guinea pig.

  20. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

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    Ji Yang eKim

    2015-09-01

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP1 plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE in the distinct brain regions. In addition, P2X7 receptor (P2X7R, an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death. Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.

  1. Effect of Argemone mexicana (L.) against lithium-pilocarpine induced status epilepticus and oxidative stress in Wistar rats.

    Science.gov (United States)

    Asuntha, G; Raju, Y Prasanna; Sundaresan, C R; Rasheed, Arun; Chowdary, V Harini; Vandana, K R; Babu, K Satish; Prasad, K V S R G

    2015-01-01

    Argemone mexicana (L.) has a role in the treatment of epileptic disorders in Indian traditional system of medicine. We studied its effect on induced status epilepticus (SE) and oxidative stress in rats. SE was induced in male albino rats by administration of pilocarpine (30 mg/kg, ip) 24 h after injection of lithium chloride (3 mEq/kg, ip). Different doses of the ethanol extract of A. mexicana were administered orally 1 h before the injection of pilocarpine. The severity of SE was observed and recorded every 15 min for 90 min and thereafter at every 30 min for another 90 min, using the Racine scoring system. In vivo lipid peroxidation of rat brain tissue was measured utilizing thiobarbiturate-reactive substances. Both in vitro free radical nitric oxide and 2,2-diphenyl-1-picryl hydrazyl scavenging activities of the extract were also determined. The SE severity was significantly reduced following oral administration of the extract at 250, 500 and 1000 mg/kg doses. None of the animals from groups 3 to 5 (with A. mexicana extract) have exhibited forelimb clonus of stage 4 seizure. The extract also exhibited both in vivo and in vitro antioxidant activities. PMID:25675709

  2. Extensive Cortical Diffusion Restriction in a 50-Year-Old Female with Hyperammonemic Encephalopathy and Status Epilepticus

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    Adam de Havenon

    2014-01-01

    Full Text Available Comorbid hyperammonemic encephalopathy (HE and status epilepticus (SE leading to extensive cortical diffusion restriction (CDR on MRI have not been previously reported. We describe a patient with HE who subsequently developed provoked SE. Sequential MRIs demonstrated a progressive CDR that involved the entire bilateral supratentorial cortex, thalami, and basal ganglia, resulting in death from cerebral edema and brain herniation. Diffuse CDR is most frequently seen after hypotension or hypoxia, which our patient did not experience. Such findings have also been described in both HE and SE (Milligan et al. (2009, Chatzikonstantinou et al. (2011, U-King-Im et al. (2011, and Bindu et al. (2009, but not to the extent seen in our patient. Additionally, our patient had distinct radiologic features of both disease processes, suggesting a cumulative effect. The diagnosis of HE and SE in the setting of extensive CDR should not be missed and could lead to improved outcomes for two progressive, malignant, and treatable illnesses that can be easily overlooked.

  3. Role of the Mitochondrial Calcium Uniporter in Rat Hippocampal Neuronal Death After Pilocarpine-Induced Status Epilepticus.

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    Wang, Cui; Xie, Nanchang; Wang, Yunlong; Li, Yulin; Ge, Xinjie; Wang, Menglu

    2015-08-01

    The mitochondrial calcium uniporter (MCU) is reportedly involved in oxidative stress, apoptosis, and many neurological diseases. However, the role of the MCU in epilepsy remains unknown. In this study, we found that the MCU inhibitor Ru360 significantly attenuated neuronal death and exerted an anti-apoptotic effect on rat hippocampal neurons after pilocarpine-induced status epilepticus (SE), while the MCU activator spermine increased seizure-induced neuronal death and apoptosis. In addition, Ru360 decreased the level of seizure-induced reactive oxygen species (ROS) in mitochondria isolated from rat hippocampi. Moreover, Ru360 restored the altered mitochondrial membrane potential and cytochrome c (CytC) release in epileptic hippocampi. However, spermine treatment exerted an opposite effect on seizure-induced ROS production and mitochondrial membrane potential alteration and CytC release compared with Ru360 treatment. Altogether, the findings of this study suggest that MCU inhibition exerts a neuroprotective effect on seizure-induced brain injury possibly through the mitochondria/ROS/CytC pathway.

  4. The differential DRP1 phosphorylation and mitochondrial dynamics in the regional specific astroglial death induced by status epilepticus

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    Ah-Reum eKo

    2016-05-01

    Full Text Available The response and susceptibility to astroglial degenerations are relevant to the distinctive properties of astrocytes in a hemodynamic-independent manner following status epilepticus (SE.Since impaired mitochondrial fission plays an important role in mitosis, apoptosis and programmed necrosis, we investigated whether the unique pattern of mitochondrial dynamics is involved in the characteristics of astroglial death induced by SE. In the present study, SE induced astroglial apoptosis in the molecular layer of the dentate gyrus, accompanied by decreased mitochondrial length. In contrast, clasmatodendritic (autophagic astrocytes in the CA1 region showed mitochondrial elongation induced by SE. Mdivi-1 (an inhibitor of mitochondrial fission effectively attenuated astroglial apoptosis, but WY14643 (an enhancer of mitochondrial fissionaggravated it. In addition, Mdivi-1accelerated clasmatodendritic changes in astrocytes. These regional specific mitochondrial dynamics in astrocytes were closely correlated with dynamin-related protein (DRP1, a mitochondrial fission protein phosphorylation, not optic atrophy 1 (a mitochondrial fusion protein expression. To the best of our knowledge, the present data demonstrate for the first time the novel role of DRP1-mediated mitochondrial fission in astroglial loss. Thus, the present findings suggest that the differential astroglial mitochondrial dynamics may participate in the distinct characteristics of astroglial death induced by SE.

  5. Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation.

    Science.gov (United States)

    Mishra, Vikas; Shuai, Bing; Kodali, Maheedhar; Shetty, Geetha A; Hattiangady, Bharathi; Rao, Xiaolan; Shetty, Ashok K

    2015-12-07

    Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy.

  6. Drugs use in 3 children patients with status epilepticus after epilepsy focus resection%3例儿童癫痫灶切除术后癫痫持续状态的药物治疗

    Institute of Scientific and Technical Information of China (English)

    齐晓涟; 李晓龙; 洪雪姣

    2013-01-01

    to find the medication problems in the treatment of children patients with status epilepticus and to improve rational use of drugs in status epilepticus. we analyzed the treatment and meidcation of 3 cases of children patients with status epilepticus after epilepsy focus resection. the patient's weight, internal environment, medication compliance ,the standard level and dose of antiepileptic drug had a certain impact on the control of status epilepticus. individualized and comprehensive treatment measures guarantee the termination of status epilepticus.%  通过对3例儿童癫痫灶切除术后癫痫持续状态的治疗经过和用药进行分析,发现儿童癫痫持续状态治疗用药中的问题,提高癫痫持续状态合理用药水平。患儿的体重,内环境,用药顺应性、抗癫痫药使用的规范程度和剂量对癫痫持续状态的控制具有一定影响。个体化和综合治疗措施是终止癫痫持续状态的保证。

  7. Assessment of effect of ethanolic extract of Tephrosia purpurea (L. Pers., Fabaceae, activity on lithium-pilocarpine induced Status epilepticus and oxidative stress in Wistar rats Avaliação do efeito do extrato etanólico da Tephrosia purpurea (L. Pers., Fabaceae, sobre o status epilepticus induzido por lítio-pilocarpina e estresse oxidativo, em ratos Wistar

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    G Asuntha

    2010-11-01

    Full Text Available Tephrosia purpurea (L. Pers., Fabaceae, is claimed to be of use in the control and treatment of a variety of epileptic disorders in Indian system of medicine. The present study plans to systematically evaluate T. purpurea and to verify this claim. Status epilepticus was induced in male albino rats of Wistar strain by administration of pilocarpine (30 mg/kg, i.p. 24 h after lithium chloride (3 mEq/kg, i.p.. Different doses of the extract of T. purpurea were administered orally one hour before the injection of pilocarpine. The severity of status epilepticus was observed and recorded every 15 min till 90 min and thereafter every 30 min till 180 min, using the scoring system. The in vivo lipid peroxidation of rat brain tissue was measured. The in vitro NO free radical scavenging activity of plant extract was assessed. The interaction between plant extract and 2-diphenyl-2-picryl hydrazyl (DPPH was also observed for in vitro free radical scavenging activity. The severity of status epilepticus was reduced with the administration of ethanolic extract of T. purpurea. Ethanolic extract of the plant exhibited both in vivo and in vitro antioxidant activity. The ethanolic extract of T. purpurea was found to be useful to control lithium-pilocarpine induced status epilepticus in albino rats of Wistar strain.Tephrosia purpurea (L. Pers., Fabaceae, é conhecida pelo seu uso no controle e tratamento de uma variedade de distúrbios epilépticos no sistema indiano de medicina. O presente estudo pretende avaliar de forma sistemática T. purpurea e verificar essa alegação. Status epilepticus foi induzido em ratos albinos machos da linhagem Wistar pela administração de pilocarpina (30 mg/kg, i.p. 24 h após o cloreto de lítio (3 mEq/kg, i.p.. Diferentes doses do extrato de T. purpurea foram administrados por via oral uma hora antes da injeção de pilocarpina. A gravidade do status epilepticus foi observada e registrada a cada 15 min até 90 min e

  8. 自身免疫性脑病相关癫痫持续状态的研究进展%Progress on Reseaches of Status Epilepticus Ralated to Autoimmune Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    杨光; 曾可斌

    2014-01-01

    Status epilepticus is the most severe form of epilepsy and as wel as a common neurological emergency associated with high mortality.The underlying causes are key factors to determine patients'prognosis.To focus on autoimmune encephalopathy,a ralative rare etiology of status epilepticus,we reviewed the progress on researches in rencent yerars,then discussed the possible pathogenesis.%癫痫持续状态(status epilepticus,SE)是最严重的癫痫发作形式,是神经科常见急症,死亡率高。它的潜在病因是决定患者预后的重要因素。针对自身免疫性脑病这一不常见SE病因,我们回顾近年来的相关研究进展,并探讨其致病机制。

  9. Status epilepticus after prolonged umbilical cord occlusion is associated with greater neural injury in [corrected] fetal sheep at term-equivalent.

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    Paul P Drury

    Full Text Available The majority of pre-clinical studies of hypoxic-ischemic encephalopathy at term-equivalent have focused on either relatively mild insults, or on functional paradigms of cerebral ischemia or hypoxia-ischemia/hypotension. There is surprisingly little information on the responses to single, severe 'physiological' insults. In this study we examined the evolution and pattern of neural injury after prolonged umbilical cord occlusion (UCO. 36 chronically instrumented fetal sheep at 125-129 days gestational age (term = 147 days were subjected to either UCO until mean arterial pressure was < = 8 mmHg (n = 29, or sham occlusion (n = 7. Surviving fetuses were killed after 72 hours for histopathologic assessment with acid-fuchsin thionine. After UCO, 11 fetuses died with intractable hypotension and 5 ewes entered labor and were euthanized. The remaining 13 fetuses showed marked EEG suppression followed by evolving seizures starting at 5.8 (6.8 hours (median (interquartile range. 6 of 13 developed status epilepticus, which was associated with a transient secondary increase in cortical impedance (a measure of cytotoxic edema, p<0.05. All fetuses showed moderate to severe neuronal loss in the hippocampus and the basal ganglia but mild cortical cell loss (p<0.05 vs sham occlusion. Status epilepticus was associated with more severe terminal hypotension (p<0.05 and subsequently, greater neuronal loss (p<0.05. In conclusion, profound UCO in term-equivalent fetal sheep was associated with delayed seizures, secondary cytotoxic edema, and subcortical injury, consistent with the predominant pattern after peripartum sentinel events at term. It is unclear whether status epilepticus exacerbated cortical injury or was simply a reflection of a longer duration of asphyxia.

  10. Lovastatin modulates glycogen synthase kinase-3β pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus.

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    Chun-Yao Lee

    Full Text Available This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β and collapsin responsive mediator protein-2 (CRMP-2 signaling pathway and mossy fiber sprouting (MFS in epileptic rats. MFS in the dentate gyrus (DG is an important feature of temporal lobe epilepsy (TLE and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis.

  11. Inhibition of sodium glucose cotransporters following status epilepticus induced by intrahippocampal pilocarpine affects neurodegeneration process in hippocampus.

    Science.gov (United States)

    Melo, Igor S; Santos, Yngrid M O; Costa, Maísa A; Pacheco, Amanda L D; Silva, Nívea K G T; Cardoso-Sousa, L; Pereira, U P; Goulart, L R; Garcia-Cairasco, Norberto; Duzzioni, Marcelo; Gitaí, Daniel L G; Tilelli, Cristiane Q; Sabino-Silva, Robinson; Castro, Olagide W

    2016-08-01

    Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, starting from secondary functional disorders due to several insults, including self-sustaining continuous seizures identified as status epilepticus (SE). Although hypoglycemia has been associated with SE, the effect of inhibition of the Na(+)/glucose cotransporters (SGLTs) on hippocampus during SE is still unknown. Here we evaluated the functional role of SGLT in the pattern of limbic seizures and neurodegeneration process after pilocarpine (PILO)-induced SE. Vehicle (VEH, 1μL) or phlorizin, a specific SGLT inhibitor (PZN, 1μL, 50μg/μL), was administered in the hippocampus of rats 30min before PILO (VEH+PILO or PZN+PILO, respectively). The limbic seizures were classified using the Racine's scale, and the amount of wet dog shakes (WDS) was quantified before and during SE. Neurodegeneration process was evaluated by Fluoro-Jade C (FJ-C), and FJ-C-positive neurons (FJ-C+) were counted 24h and 15days after SE. The PZN-treated rats showed higher (pclass 5 seizures repeated themselves more times (pclasses in the PZN group at 50min after SE induction. The PZN+PILO animals had a higher (p<0.05) number of FJ-C+ cells in the dentate gyrus (DG), hilus, and CA3 and CA1 of hippocampus, when compared with VEH+PILO. The PZN+PILO animals had a decreased number (p<0.05) of FJ-C+ cells in CA1 compared with VEH+PILO 15days after SE induction. Taken together, our data suggest that SGLT inhibition with PZN increased the severity of limbic seizures during SE and increased neurodegeneration in hippocampus 24h after SE, suggesting that SGLT1 and SGLT2 could participate in the modulation of earlier stages of epileptogenic processes. PMID:27429292

  12. Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus.

    Science.gov (United States)

    Vinet, Jonathan; Vainchtein, Ilia D; Spano, Carlotta; Giordano, Carmela; Bordini, Domenico; Curia, Giulia; Dominici, Massimo; Boddeke, Hendrikus W G M; Eggen, Bart J L; Biagini, Giuseppe

    2016-08-01

    Activated microglia, astrogliosis, expression of pro-inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro-inflammatory cytokines with the activated morphology of microglia, attributing them a pro-epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates. Here, we used a FACS-based approach to discriminate between microglia and myeloid infiltrates isolated from the hippocampus 24 h and 96 h after status epilepticus (SE) in pilocarpine-treated CD1 mice. We observed that microglia do not express MHCII whereas myeloid infiltrates express high levels of MHCII and CD40 96 h after SE. This antigen-presenting cell phenotype correlated with the presence of CD4(pos) T cells. Moreover, microglia only expressed TNFα 24 h after SE while myeloid infiltrates expressed high levels of IL-1β and TNFα. Immunofluorescence showed that astrocytes but not microglia expressed IL-1β. Myeloid infiltrates also expressed matrix metalloproteinase (MMP)-9 and 12 while microglia only expressed MMP-12, suggesting the involvement of both cell types in the BBB leakage that follows SE. Finally, both cell types expressed the phagocytosis receptor Axl, pointing to phagocytosis of apoptotic cells as one of the main functions of microglia. Our data suggests that, during early epileptogenesis, microglia from the hippocampus remain rather immune supressed whereas myeloid infiltrates display a strong inflammatory profile. GLIA 2016 GLIA 2016;64:1350-1362. PMID:27246930

  13. Modificação do metodo "kindling" para obtenção de status epilepticus experimental em ratos

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    Carlos J. Reis de Campos

    1980-03-01

    Full Text Available Foi utilizada em nova espécie animal (ratos, uma modificação do método "kindling", introduzida por Taber e col. (1977 para obtenção de status epilepticus experimental. Para isso foram implantados mediante cirurgia estereotáxica, eletrodos duplos, torcidos no hipocampo dorsal de 12 ratos machos albinos. Esses animais foram submetidos, após uma semana de pós-operatório, a 1 segundo de estimulação elétrica de baixa intensidade em forma intermitente, um estímulo por minuto durante 2 horas, desenvolvendo-se em prazo de 30 minutos um estado de epilepsia eletrográfica e comportamental duradoura. Vários padrões de descargas epilépticas eletrográficas foram observados bem como manifestações convulsivas tônico-clônicas. Os animais que foram submetidos a novas sessões de estimulação após 7 e 14 dias mostraram aumento de atividade epiléptica demonstrando uma modificação plástica do hipocampo do rato submetido a estimulação elétrica a qual perdura no tempo. O método permite a obtenção de "kindling" em tempo bem mais curto (horas, comparativamente às técnicas anteriormente descritas (dias, tornando-se um promissor modelo de epilepsia para testes de drogas anticonvulsivantes e para o estudo dos mecanismos fisiopatológicos e bioquímicos envolvidos na descarga epiléptica.

  14. The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy.

    Science.gov (United States)

    Grabenstatter, H L; Del Angel, Y Cruz; Carlsen, J; Wempe, M F; White, A M; Cogswell, M; Russek, S J; Brooks-Kayal, A R

    2014-02-01

    Pilocarpine-induced status epilepticus (SE), which results in temporal lobe epilepsy (TLE) in rodents, activates the JAK/STAT pathway. In the current study, we evaluate whether brief exposure to a selective inhibitor of the JAK/STAT pathway (WP1066) early after the onset of SE affects the severity of SE or reduces later spontaneous seizure frequency via inhibition of STAT3-regulated gene transcription. Rats that received systemic WP1066 or vehicle at the onset of SE were continuously video-EEG monitored during SE and for one month to assess seizure frequency over time. Protein and/or mRNA levels for pSTAT3, and STAT3-regulated genes including: ICER, Gabra1, c-myc, mcl-1, cyclin D1, and bcl-xl were evaluated in WP1066 and vehicle-treated rats during stages of epileptogenesis to determine the acute effects of WP1066 administration on SE and chronic epilepsy. WP1066 (two 50mg/kg doses) administered within the first hour after onset of SE results in transient inhibition of pSTAT3 and long-term reduction in spontaneous seizure frequency. WP1066 alters the severity of chronic epilepsy without affecting SE or cell death. Early WP1066 administration reduces known downstream targets of STAT3 transcription 24h after SE including cyclin D1 and mcl-1 levels, known for their roles in cell-cycle progression and cell survival, respectively. These findings uncover a potential effect of the JAK/STAT pathway after brain injury that is physiologically important and may provide a new therapeutic target that can be harnessed for the prevention of epilepsy development and/or progression. PMID:24051278

  15. 咪达唑仑治疗癫痫持续状态的临床探析%The Clinical Investigation on Midazolam Treatment of Status Epilepticus

    Institute of Scientific and Technical Information of China (English)

    耿志伟

    2015-01-01

    ObjectiveThe clinical efficacy of Midazolam treatment of status epilepticus is to be analyzed.Methods Choose 90 cases status epilepticus patients who are treated in hospital from July 2012 to October 2014 and separate them into control group and study group at random. Patients in control group are given diazepam treatment. While,patients in study group are given Midazolam treatment; and then observe and compare the patients’ side-effect condition and their clinical symptoms of two groups after the treatment.Results For patients in control group,the side-effect incidence is 17.8% and treatment efficiency is 86.7%; while,for patients in study group,the side-effect incidence is 8.9% and treatment efficiency is 95.6%,there is a treatment differential between the two groups,and such a differential has statistic value(P<0.05).Conclusion Midazolam treatment is quite effective to cure status epilepticus with few poisoning by-effect and side effect,therefore,it is rather worthwhile to be clinicaly promoted and applied in treatment of status epilepticus.%目的:对咪达唑仑治疗癫痫持续状态的治疗效果进行探究。方法选取我院于2012年17月~2014年10月收治的90例癫痫持续状态患者随机分成对照组和治疗组,对照组患者采用地西泮治疗,治疗组采用咪达唑仑治疗,对两组患者治疗后不良反应发生情况和临床症状进行分析比较。结果经过治疗,对照组的不良反应发生率为17.8%,治疗总有效率为86.7%;治疗组的不良反应发生率为8.9%,治疗总有效率为95.6%,两组结果对比差异显著。结论采用咪达唑仑治疗癫痫持续状态治疗效果显著,并且毒副作用小,不良发应情况少。

  16. Application of anesthetic drugs in the therapy of status epilepticus%麻醉药在癫痫持续状态治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    陈一萌; 韩冲芳

    2014-01-01

    Status epilepticus is a common neurological emergency and associated with high morbidity and mortality.Refractory status epilepticus describes continuing seizures despite adequate initial pharmacologic treatment and requiring general anaesthesia .The anesthetic drugs include midazolam ,propofol , ketamine,pentobarbital, thiopental, lidocaire, isoflurane and desflurance.It is necessary to know the pharmacological function ,usage and adverse reactions of the anesthetic drugs .%癫痫持续状态是神经系统的急症,有较高的发病率与致死率。难治性癫痫持续状态是指尽管用了足够剂量的初始药物仍然不能控制发作的情况,需要应用麻醉方法。这些麻醉药包括咪达唑仑、丙泊酚、氯胺酮、戊巴比妥钠、硫喷妥钠、利多卡因、异氟醚与地氟醚。了解这些麻醉药治疗难治性癫痫持续状态的药理作用、用法与不良反应是非常必要的。

  17. Clinical study status epilepticus related factors%癫痫持续状态相关因素的临床研究

    Institute of Scientific and Technical Information of China (English)

    付海红; 范卫明

    2016-01-01

    目的:探讨癫痫持续状态发病的相关危险因素,为癫痫持续状态的治疗提供参考。方法回顾性分析2013年1月至2015年1月滨州医学院附属医院神经内科住院治疗的癫痫持续状态患者,共纳入72例,收集患者的临床资料。对所有患者进行随访,采用格拉斯哥预后评分评价患者预后情况,分析与预后相关的危险因素。结果患者男女性别之比为4.54:1,男性发病率显著高于女性(X2=43.581,P<0.01);儿童占29.17%,成人占70.83%,成人的发病率显著高于儿童(X2=42.335,P<0.01);CSE63例,NCSE9例,CSE的发病率显著高于NCSE,差异有统计学意义(X2=46.611,P<0.01);颅脑损伤、病毒性脑炎急性期和脑血管病变是癫痫持续状态发病的危险因素。结论癫痫持续状态在各年龄段均可见,成人发病率高于儿童,男性高于女性,颅脑损伤、病毒性脑炎急性期和脑血管病变是癫痫持续状态发病的危险因素。%Objective To investigate the status epilepticus associated risk factors, provide a reference for the treatment of status epilepticus. Methods A retrospective analysis of epilepsy from January 2013 to January 2015, Affiliated Hospital of Binzhou Medical College, Department of Neurology, continued state of patients hospitalized, 72 cases were included collecting clinical data. All patients were followed up, using the Glasgow Outcome Scale evaluate the prognosis of patients and to analyze the risk factors associated with prognosis. Results Patients gender ratio of 4.54: 1, male incidence was significantly higher than women (X2= 43.581, P <0.01); children account for 29.17%, accounting for 70.83 percent of adult incidence was significantly higher than adult children (X2=42.335 , P<0.01);CSE63 cases, NCSE9 example, CSE incidence was significantly higher than NCSE, the difference was statistically significant (X2=46.611, P<0.01);traumatic brain injury, acute

  18. Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats.

    Science.gov (United States)

    Malkin, Sergey L; Amakhin, Dmitry V; Veniaminova, Ekaterina A; Kim, Kira Kh; Zubareva, Olga E; Magazanik, Lev G; Zaitsev, Aleksey V

    2016-07-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study. The changes in AMPA receptor subunit composition were investigated in several brain areas, including the medial prefrontal cortex (mPFC), the temporal cortex (TC), and the dorsal (DH) and ventral hippocampus (VH) during the first week following pilocarpine-induced status epilepticus (PILO-induced SE). In the hippocampus, GluA1 and GluA2 mRNA expression slightly decreased after PILO-induced SE and returned to the initial level on the seventh day. We did not detect any significant changes in mRNA expression of the GluA1 and GluA2 subunits in the TC, whereas in the mPFC we observed a significant increase of GluA1 mRNA expression on the third day and a decrease in GluA2 mRNA expression during the entire first week. Accordingly, the GluA1/GluA2 expression ratio increased in the mPFC, and the functional properties of the pyramidal cell excitatory synapses were disturbed. Using whole-cell voltage-clamp recordings, we found that on the third day following PILO-induced SE, isolated mPFC pyramidal neurons showed an inwardly rectifying current-voltage relation of kainate-evoked currents, suggesting the presence of GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). IEM-1460, a selective antagonist of CP-AMPARs, significantly reduced the amplitude of evoked EPSC in pyramidal neurons from mPFC slices on the first and third days, but not on the seventh day. The antagonist had no effects on EPSC amplitude in slices from control animals. Thus, our data demonstrate that PILO-induced SE affects subunit composition of AMPARs in different brain areas, including the mPFC. SE induces transient (up to few days) incorporation of CP-AMPARs in the excitatory synapses of mPFC pyramidal neurons, which may disrupt normal circuitry functions. PMID:27109923

  19. 丙泊酚治疗难治性癫痫持续状态的疗效分析%Curative Effect of Propofol in Treatment of Refractory Status Epilepticus

    Institute of Scientific and Technical Information of China (English)

    黄德; 谢向前

    2014-01-01

    目的:观察丙泊酚治疗难治性癫痫持续状态的临床疗效。方法:选择笔者所在医院科室收治的难治性癫痫持续状态患者23例,均予以丙泊酚为主的综合治疗。结果:所有难治性癫痫持续状态患者均于治疗后36 h内得到有效控制,有效率100%,23例患者均未出现明显的不良反应。结论:丙泊酚是治疗难治性癫痫持续状态有效而安全的方法,值得临床推广和应用。%Objective:To observe the clinical efficacy of propofol in treatment of refractory status epilepticus.Method:The clinical data of patients with refractory status epilepticus were retrospective analyzed,23 cases were to be propofol combined therapy.Result:All patients with refractory status epilepticus were within 36 hours after treatment had been effectively controlled,the effective rate was 100%,23 cases were no obvious adverse reactions.Conclusion:Refractory status epilepticus treated with propofol is effective and safe,and worthy of promotion and application.

  20. Antagonist targeting microRNA-155 protects against lithium-pilocarpine-induced status epilepticus in C57BL/6 mice by activating brain-derived neurotrophic factor

    Directory of Open Access Journals (Sweden)

    Zhengxu eCai

    2016-05-01

    Full Text Available Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155 could serve as a promising treatment of mesial temporal lobe epilepsy (MTLE. In the current study, the therapeutic potential of miR-155 antagonist against TLE was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG recordings. The expression of brain-derived neurotrophic factor (BDNF and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study.

  1. Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-κB activation-induced nitric oxide synthase II expression.

    Science.gov (United States)

    Chang, Chiung-Chih; Chen, Shang-Der; Lin, Tsu-Kung; Chang, Wen-Neng; Liou, Chia-Wei; Chang, Alice Y W; Chan, Samuel H H; Chuang, Yao-Chung

    2014-02-01

    Status epilepticus induces subcellular changes that may eventually lead to neuronal cell death in the hippocampus. Based on an animal model of status epilepticus, our laboratory showed previously that sustained hippocampal seizure activity activates nuclear factor-κB (NF-κB) and upregulates nitric oxide synthase (NOS) II gene expression, leading to apoptotic neuronal cell death in the hippocampus. The present study examined the potential modulatory role of heat shock protein 70 (HSP70) on NF-κB signaling in the hippocampus following experimental status epilepticus. In Sprague-Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Expression of HSP70 was elevated as early as 1h after the elicitation of sustained seizure activity, followed by a progressive elevation that peaked at 24h. Pretreatment with an antisense oligonucleotide against hsp70 decreased the HSP70 expression, and significantly augmented IκB kinase (IKK) activity and phosphorylation of IκBα, alongside enhanced nuclear translocation and DNA binding activity of NF-κB in the hippocampal CA3 neurons and glial cells. These cellular events were followed by enhanced upregulation of NOS II and peroxynitrite expression 3h after sustained seizure activity that led to an increase of caspase-3 and DNA fragmentation in the hippocampal CA3 neurons 7days after experimental status epilepticus. We concluded that HSP70 protects against apoptotic cell death induced by NF-κB activation and NOS II-peroxynitrite signaling cascade in the hippocampal CA3 and glial cells following experimental status epilepticus via suppression of IKK activity and deactivation of IκBα.

  2. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study

    Science.gov (United States)

    2014-01-01

    Introduction Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. Methods We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year. Results Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5

  3. 小儿癫痫持续状态的治疗进展%The Treatment Advancement of Status Epilepticus in Children

    Institute of Scientific and Technical Information of China (English)

    马建南

    2012-01-01

    癫痫持续状态( Status Epilepticus,SE)是一种在儿科常见的威胁生命的神经系统急症,其发病率为每年18/10万人~23/10万人,病死率为2%~6%[1].有证据表明,痫性发作持续时间越长,患儿对抗癫痫药物的敏感性越低,控制发作的可能性越小.因此,在临床上需要尽早识别和规范治疗癫痫持续状态.

  4. Status Epilepticus:Update on Treatment%第一节癫痫持续状态的治疗进展(上)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ 癫痫持续状态(Status Epilepticus,SE)是指一次癫痫发作持续30分钟以上者,或者虽有间歇期,但意识不能恢复,反复频繁发作30分钟以上,就称癫痫持续状态.若癫痫发作频繁,连续多次不止,但间歇期意识恢复,生命体征正常,则称连续性癫痫发作.SE约占癫痫患者的3%~6%,是一种危险的急症,应及时送往医院抢救.

  5. Clinical and EEG characteristics in children with status epilepticus%小儿癫癎持续状态临床与脑电图特点

    Institute of Scientific and Technical Information of China (English)

    张双; 包新华; 刘寅; 曹丽华; 庞保东; 吴家骅

    2006-01-01

    @@ 癫癎持续状态(status epilepticus,SE)是威胁生命的神经科急症之一,占癫癎患儿的 2.6%~6%,根据临床发作形式分为惊厥性(CSE)和非惊厥性癫癎持续状态(NCSE)[1].对 CSE国内外有诸多报告.NCSE的临床、脑电图有一定的特殊性,容易漏诊或误诊,近年来受到广泛重视,但国内报道较少.我院近4年共收治SE患儿36例,现报告如下.

  6. Status epilepticus and cardiopulmonary arrest in a patient with carbon monoxide poisoning with full recovery after using a neuroprotective strategy: a case report

    Directory of Open Access Journals (Sweden)

    Abdulaziz Salman

    2012-12-01

    Full Text Available Abstract Introduction Carbon monoxide poisoning can be associated with life-threatening complications, including significant and disabling cardiovascular and neurological sequelae. Case presentation We report a case of carbon monoxide poisoning in a 25-year-old Saudi woman who presented to our facility with status epilepticus and cardiopulmonary arrest. Her carboxyhemoglobin level was 21.4 percent. She made a full recovery after we utilized a neuroprotective strategy and normobaric oxygen therapy, with no delayed neurological sequelae. Conclusions Brain protective modalities are very important for the treatment of complicated cases of carbon monoxide poisoning when they present with neurological toxicities or cardiac arrest. They can be adjunctive to normobaric oxygen therapy when the use of hyperbaric oxygen is not feasible.

  7. Comparison of short-term effects of midazolam and lorazepam in the intra-amygdala kainic acid model of status epilepticus in mice.

    Science.gov (United States)

    Diviney, Mairead; Reynolds, James P; Henshall, David C

    2015-10-01

    Benzodiazepines remain as the first-line treatment for status epilepticus (SE), but debate continues as to the choice and delivery route of pharmacotherapy. Lorazepam is currently the preferred anticonvulsant for clinical use, but midazolam has become a popular alternative, particularly as it can be given by nonintravenous routes. Anticonvulsants are also commonly used to terminate SE in animal models. Here, we aimed to compare the efficacy of midazolam with that of lorazepam in an experimental model of focal-onset SE. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in 8week old C57Bl/6 mice. Forty minutes later, mice were treated with an intraperitoneal injection of either lorazepam or midazolam (8mg/kg). Electroencephalogram (EEG) activity, histology, and behavioral tests assessing recovery of function were evaluated and compared between groups. Intraperitoneal injection of either lorazepam or midazolam resulted in similar patterns of reduced EEG epileptiform activity during 1-hour recordings. Damage to the hippocampus and presentation of postinsult anxiety-related behavior did not significantly differ between treatment groups at 72h. However, return of normal behaviors such as grooming, levels of activity, and the evaluation of overall recovery of SE mice were all superior at 24h in animals given midazolam compared with lorazepam. Our results indicate that midazolam is as effective as lorazepam as an anticonvulsant in this model while also providing improved animal recovery after SE. These data suggest that midazolam might be considered by researchers as an anticonvulsant in animal models of SE, particularly as it appears to satisfy the requirements of refining procedures involving experimental animals at early time-points after SE.

  8. 癫痫持续状态的临床救治分析%Clinical analysis of treatment of status epilepticus

    Institute of Scientific and Technical Information of China (English)

    吴海燕

    2011-01-01

    Objective To investigate the causes, treatment methods and clinical efficacy of status epilepticus( SE). Methods Totally 60 cases of SE patients were retrospectively analyzed. Results SE control time (from drugs to symptoms) in 5 ~ 60min 36, 60 ~ 360min 20 cases, more than 360min 4 cases. Cured 57 patients(95% ) , 3 cases(5% ). Conclusions The combination of early onset of diazepam and phenobarbital for the control of the disease can have better results , can not control the use of thiopental anesthesia treatment to stable condition, the clinical observation that in time, the rapid rescue, is the key to control status epilepticus, to improve their prognosis.%目的 探讨癫痫持续状态(SE)的病因、临床救治的方法及疗效.方法 对60例SE患者的资料进行回顾性分析.结果 SE控制时间(从用药至症状消失)在5~60min 36例,60~360min 20例,大于360min4例.治愈57例(95%),无效3例(5%).结论 发作初期联合应用地西泮和苯巴比妥钠对控制病情能起到较好效果,无法控制时使用硫喷妥钠麻醉治疗能基本稳定病情,经临床观察证明,及时处理,抢救迅速,是控制癫痫持续状态、改善其预后的关键.

  9. CLINICAL RESEARCH ON LARGE DOSE OF CHLORPROMAZINE IN THE TREATMENT OF STATUS EPILEPTICUS%大剂量氯丙嗪治疗癫痫持续状态的临床研究

    Institute of Scientific and Technical Information of China (English)

    卢桂兰; 蔡毅; 曾志文

    2011-01-01

    [目的]探讨大剂量氯丙嗪治疗癫痫持续状态的疗效.[方法]予氯丙嗪25~50 mg加入生理盐水l00ml中静滴,0.83 mg/min.[结果]经大剂量氯丙嗪治疗后,患者于30~60 min内癫痫持续状态控制.[结论]大剂量氯丙嗪可治疗癫痫持续状态.%[Objective] To explore the effectiveness of high-dose chlorpromazine in the treatment of status epilepticus. [Methods] Mixed 25-50mg chlorpromazine with 100 ml normal saline solution and injected intravenously, 0.83mg per minute. [Results] With large doses of chlorpromazine treatment, status epilepticus would be under control within the 30-60 minutes. [Conclusion] Large dose of chlorpromazine can be used to treat status epilepticus.

  10. Progresses in studies on nonconvulsive status epilepticus in critically ill children%危重症患儿非惊厥性癫(疒间)持续状态的研究进展

    Institute of Scientific and Technical Information of China (English)

    张赟健; 王艺; 孙道开

    2011-01-01

    @@ 癫(疒间)持续状态(status epilepticus,SE)是神经科危重症,尤其多见于婴幼儿.根据不同临床表现可分为惊厥性SE(convulsive status epilepticus,CSE)和非惊厥性SE(nonconvulsive status epilepticus,NCSE)[1].人们对前者有较深刻的认识,其对小儿危害较大;但后者因无惊厥发作且临床表现复杂多样,常被漏诊或误诊为病毒性脑炎、精神病、癔病等,而延误治疗致不可逆性脑损伤.危重症患儿由于多器官功能障碍以及内环境紊乱更易发生NCSE,近年来床旁长程脑电监测已能有效地检出危重症患儿NCSE的发作[2],这些患儿本身已存在神经系统损伤,因SE发作可导致大脑的二次损伤,应引起高度重视.

  11. Application of clinical pathway in intensive and critical care of patients with status epilepticus%临床路径在癫痫持续状态患者急救中的应用

    Institute of Scientific and Technical Information of China (English)

    罗先海; 陈万

    2012-01-01

    目的 探讨临床路径工作模式在癜痫持续状态抢救治疗中的应用价值.方法 对2007年11月~2009年10月收治的35例癫痫持续状态患者,按制定的临床路径表作急诊抢救并对临床资料进行分析.结果 35例患者中28例癫痫发作被控制,病人逐渐清醒;2例放弃治疗;死亡5例.结论 临床路径的应用可缩短大发作时间,提高抢救的成功率,减轻患者及家属经济负担.%Objective To evaluate the value of clinical pathway in intensive and critical care of patients with status epilepticus. Methods Data of intensive and critical caring on the basis of clinical pathway table of 35 patients with status epilepticus were studied retrospectively. Results 28 patients were effective controlled, 2 patients were withdrew from treatment, and 5 patients died. Conclusion The clinical pathway can shorten the course of status epilepticus, improve the success rate of rescue, and reduce costs if we follow the clinical pathway.

  12. Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage.OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE).DESIGN: Contrast observation.SETTING: Department of Pediatrics, the First Hospital of Jilin University.PARTICIPANTS: The participants in present study were 96 patients withsevere viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion,nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG)abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56).METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked,those five drugs were given alternatively; however, those were not given if the convulsion did not attack.Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the

  13. 癫痫持续状态的发病危险因素分析%Analysis of Risk Factors in Status Epilepticus Patients

    Institute of Scientific and Technical Information of China (English)

    苗锐; 康静; 王莉; 刘学东; 邓艳春

    2011-01-01

    Objective: To investigate the risk factors of Status Epilepticus.Methods: Retrospective analysis was used to analyze the clinical data of SE patients from Department of Neurology of Xijing Hospital between January 1999 and November 2009.Logistic regression analysis was performed to determine significant contributors to SE.Results: 98 cases of SE patients were chosen, the data shows that men, adult and CSE patients are at higher risk than that of women, children and NCSE respectively.Logistic regression shows that the main risk factors for SE were central nervous system infectious(OR of 4.74), cerebro-vascular diseases(OR of 3.93),brain injury (OR of 1.84).Conclusion: The main risk factors of Status Epilepticus are central nervous system infectious, cerebro -vascular diseases and trauma.The upper respiratory infection with fever may be the most frequently incentive of Status Epilepticus in patients with epilepsy history.To avoid the trauma, prevent infection, adhere to take antiepileptic drugs in epileptieus patients, reduce various adverse incentives are the key measures to prevent SE.%目的:探讨癫痫持续状态的发病危险因素.方法:对西京医院神经内科2000年1月至2009年11月连续登记住院的癫痫持续状态患者的临床资料进行回顾性分析,采用条件logistic回归方法筛选癫痫持续状态的危险因素.结果:共收集98例癫痫持续状态患者,一般情况显示:男性发病率明显高于女性,成人发病率明显高于儿童,CSE发生率明显高于NCSE;logistic回归结果显示:中枢神经系统感染(OR值为4.74)为SE的主要危险因素,其次为脑血管痛(OR值为3.93)和颅脑外伤(OR值为1.84).SE发作的有明显诱因的占19例,其中上呼吸道感染伴发热者比例较高.结论:中枢神经系统感染、脑血管病、脑外伤是癫痫持续状态最主要的危险因素,急性上呼吸道感染伴发热者最常见的诱因.预防感染、防治脑血管病、避免外伤,减少各种诱因是预防本病的关键.

  14. New-onset refractory status epilepticus in an adult with an atypical presentation of cat-scratch disease: successful treatment with high-dose corticosteroids.

    Science.gov (United States)

    Laswell, Emily M; Chambers, Kasandra D; Whitsel, Danielle R; Poudel, Kiran

    2015-06-01

    New-onset refractory status epilepticus (NORSE) is defined as a sudden onset of refractory status epilepticus in patients who do not have a history of epilepsy. It is a neurologic emergency, and determining the underlying etiology is an important factor for effectively managing and predicting the prognosis of NORSE. We describe the case of a 28-year-old woman who was hospitalized with NORSE secondary to an unknown etiology. She did not respond to traditional anticonvulsant therapy, including benzodiazepines, fosphenytoin, propofol, and levetiracetam. The patient was placed on continuous electroencephalography (EEG) monitoring and was treated further with multiple antiepileptics, which were titrated aggressively based on EEG readings and therapeutic drug levels; despite this treatment, EEG monitoring revealed continued seizures. Thus, high-dose corticosteroids were started for seizure control. Her workup included computed tomography and magnetic resonance imaging of the head, a lumbar puncture, toxicology screening, and extensive testing for multiple infectious and inflammatory etiologies. The patient's history revealed recent exposure to a new cat. Serologic results were positive for Bartonella henselae, and she was diagnosed with cat-scratch disease (CSD). She did not have the typical presentation of symptoms of lymphadenopathy, however, which is common in CSD. Doxycycline 100 mg and rifampin 300 mg twice daily were added to the patient's anticonvulsant and corticosteroid therapy. She was hospitalized for a total of 26 days and discharged with only minor neurologic impairment (short-term memory deficits and minor cognitive problems). The patient was discharged receiving antiepileptics, antibiotics, and a corticosteroid taper. To our knowledge, this is the first clinically known case of NORSE secondary to CSD without typical CSD symptoms in the adult population. The patient failed to respond to traditional anticonvulsant therapy alone. With the addition of high

  15. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

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    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

  16. One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death

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    Ling-Lin Chen; Hang-Feng Feng; Xue-Xia Mao; Qing Ye; Ling-Hui Zeng

    2013-01-01

    Determining the minimal duration of status epilepticus (SE) that leads to the development of subsequent spontaneous seizures (i.e.,epilepsy) is important,because it provides a critical time-window for seizure intervention and epilepsy prevention.In the present study,male ICR (Imprinting Control Region) mice were injected with pilocarpine to induce acute seizures.SE was terminated by diazepam at 10 min,30 min,1 h,2 h and 4 h after seizure onset.Spontaneous seizures occurred in the 1,2 and 4 h SE groups,and the seizure frequency increased with the prolongation of SE.Similarly,the Morris water maze revealed that the escape latency was significantly increased and the number of target quadrant crossings was markedly decreased in the 1,2 and 4 h SE groups.Robust mossy fiber sprouting was observed in these groups,but not in the 10 or 30 min group.In contrast,Fluoro-Jade B staining revealed significant cell death only in the 4 h SE group.The incidence and frequency of spontaneous seizures were correlated with Timm score (P =0.004) and escape latency (P =0.004).These data suggest that SE longer than one hour results in spontaneous motor seizures and memory deficits,and spontaneous seizures are likely associated with robust mossy fiber sprouting but not neuronal death.

  17. The Effects of Quinacrine, Proglumide, and Pentoxifylline on Seizure Activity, Cognitive Deficit, and Oxidative Stress in Rat Lithium-Pilocarpine Model of Status Epilepticus

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    Mohammad Ahmad

    2014-01-01

    Full Text Available The present data indicate that status epilepticus (SE induced in adult rats is associated with cognitive dysfunctions and cerebral oxidative stress (OS. This has been demonstrated using lithium-pilocarpine (Li-Pc model of SE. OS occurring in hippocampus and striatum of mature brain following SE is apparently due to both the increased free radicals production and the limited antioxidant defense. Pronounced alterations were noticed in the enzymatic, glutathione-S transferase (GST, catalase (CAT, and superoxide dismutase (SOD, as well as in the nonenzymatic; thiobarbituric acid (TBARS and reduced glutathione (GST, indices of OS in the hippocampus and striatum of SE induced animals. Quinacrine (Qcn, proglumide (Pgm, and pentoxifylline (Ptx administered to animals before inducing SE, were significantly effective in ameliorating the seizure activities, cognitive dysfunctions, and cerebral OS. The findings suggest that all the drugs were effective in the order of Ptx < Pgm < Qcn indicating that these drugs are potentially antiepileptic as well as antioxidant; however, further studies are needed to establish this fact. It can be assumed that these antiepileptic substances with antioxidant properties combined with conventional therapies might provide a beneficial effect in treatment of epilepsy through ameliorating the cerebral OS.

  18. [A case of rhabdomyolysis after status epilepticus without stroke-like episodes in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes].

    Science.gov (United States)

    Yokoyama, Jun; Yamaguchi, Hiroo; Shigeto, Hiroshi; Uchiumi, Takeshi; Murai, Hiroyuki; Kira, Jun-ichi

    2016-01-01

    A 24-year-old man was referred to our hospital emergency department due to a sudden onset of convulsions after drinking. On arrival he presented status epilepticus and was managed by artificial ventilation. He had no brainstem signs or meningeal irritation. Head MRI showed an old infarction-like lesion in the left occipital lobe, but no abnormal signals on diffusion-weighted images. The patient showed acute rhabdomyolysis (CK 18,000 IU/l) and renal failure, and hemodialysis was started. On 18 day after admission, he was transferred to our department with mild proximal limb muscle weakness and bilateral sensorineural hearing impairment. Electroencephalography demonstrated diffuse intermittent slow wave activities. We suspected a mitochondrial disease because of a significant increase in the lactate/pyruvate ratio (24.1) in the spinal fluid, and identified A3243G mutations in mitochondrial DNA (heteroplasmy 20%) in peripheral white blood cells. We diagnosed his illness as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This is a rare case presenting an acute onset of rhabdomyolysis following alcohol intake related to A3243G mitochondrial mutation without preceding stroke-like episodes. PMID:26960270

  19. Expressions of tumor necrosis factor alpha and microRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy.

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    Ashhab, Muhammad Usman; Omran, Ahmed; Kong, Huimin; Gan, Na; He, Fang; Peng, Jing; Yin, Fei

    2013-11-01

    Recently, the role of inflammation has attracted great attention in the pathogenesis of mesial temporal lobe epilepsy (MTLE), and microRNAs start to emerge as promising new players in MTLE pathogenesis. In this study, we investigated the dynamic expression patterns of tumor necrosis factor alpha (TNF-α) and microRNA-155 (miR-155) in the hippocampi of an immature rat model of status epilepticus (SE) and children with MTLE. The expressions of TNF-α and miR-155 were significantly upregulated in the seizure-related acute and chronic stages of MTLE in the immature rat model and also in children with MTLE. Modulation of TNF-α expression, either by stimulation using myeloid-related protein (MRP8) or lipopolysaccharide or inhibition using lenalidomide on astrocytes, leads to similar dynamic changes in miR-155 expression. Our study is the first to focus on the dynamic expression pattern of miR-155 in the immature rat of SE lithium-pilocarpine model and children with MTLE and to detect their relationship at the astrocyte level. TNF-α and miR-155, having similar expression patterns in the three stages of MTLE development, and their relationship at the astrocyte level may suggest a direct interactive relationship during MTLE development. Therefore, modulation of the TNF-α/miR-155 axis may be a novel therapeutic target for the treatment of MTLE. PMID:23636891

  20. [Abnormal cerebral blood flow distributions during the post-ictal phase of febrile status epilepticus in three pediatric patients measured by arterial spin labeling perfusion MRI].

    Science.gov (United States)

    Hirano, Keiko; Fukuda, Tokiko

    2016-05-01

    The ability to visualize brain perfusion is important for identifying epileptic foci. We present three pediatric cases showing asymmetrical cerebral blood flow (CBF) distributions during the post-ictal phase of febrile status epilepticus measured by arterial spin labeling (ASL) perfusion MRI. During the acute phase, regional CBF measurements in the areas considered including epileptic foci were higher than in the corresponding area of the contralateral hemisphere, though the exact quantitative value varied between cases. We could not identify the correct epileptogenic foci, because those ASL images were taken after the prolonged and extraordinary activation of neurons in the affected area. During the recovery phase, the differences reduced and the average regional CBF measurement was 54.6 ± 6.1 ml/100 g per minute, which was a little less than the number of previous ASL studies. ASL perfusion MRI imaging provides a method for evaluating regional CBF by using magnetically labeled arterial blood water as an endogenous tracer. With this technique, we can repeatedly evaluate both the brain structure and the level of perfusion at the same time. ASL is noninvasive and easily accessible, and therefore it could become a routine tool for assessment of perfusion in daily practice of pediatric neurology.

  1. Monitoring of one case with viral encephalitis status complicated with status epilepticus cholestatic jaundice%1例病毒性脑炎癫痫持续状态并发淤积性黄疸病人的监护

    Institute of Scientific and Technical Information of China (English)

    张鑫; 刘芳

    2009-01-01

    @@ 病毒性脑炎伴癫痫持续状态已是脑实质损伤的严重临床表现[1].癫痫持续状态(status epilepticus,SE)是指癫痫发作超过30 min或2次以上连续发作,发作间期意识不恢复[2],是神经科常见急症之一,目前国际资料表明病死率达5%~15%,致残率39%~59%,后遗症状以不同程度的智力障碍最明显,持续时间越长,其致残率及病死率亦越高.

  2. Cognitive Function and Influencing Factors in Patients with Status Epilepticus%癫痫持续状态后患者的认知功能及其影响因素

    Institute of Scientific and Technical Information of China (English)

    王丹; 黄芩; 王文敏

    2011-01-01

    Objective To investigate the cognitive function and influencing factors in patients with status epilepticus. Methods We collected 20 cases of patients with status epilepticus, and compared them with the control group. We asscessed the cognitive function of them and analyzed the related influencing factors of cognitive function. Mini-mental state (MMSE) , Digital span test (DST) , Digital symbol test (DST) , Trail making test (TMT) , Verbal fluency test ( VFT) were applied to evaluate the cognitive function of patients with status epilepticus. Results (1) Cognitive features: Neuropsychologic test scores of patients with status epilepticus were lower than normal control group by applying with MMSE, DST of WAIS-R, DST, TMT and VFT, and the differences were statistically significant (P<0.0l). (2) Influencing factors of congnitive function: Level of education, age and the number of medication were, the main factors affecting cognitive function of patients with status epilepticus by multivariate stepwise regression analysis, particular level of education was the most evident. Conclusions Patients with status epilepticus have cognitive impairment. Level of education, age and the number of drugs have an impact on cognitive function, and education level is the major influencing factor of cognitive function.%目的 探讨癫痫持续状态后患者的认知功能及其影响因素.方法 收集20例癫痫持续状态后患者作认知功能评估,并与正常对照组对照,分析影响认知功能的相关因素.认知功能评估采用简明精神状态量表,韦氏成人智力量表(WAIS-R)中的数字广度,数字符号转换测验,连线测验,言语流畅性测验.结果 (1)认知功能特点:癫痫持续状态后患者的简明精神状态量表,WAIS-R中的数字广度测验,WAIS-中的数字符号转换测验,连线测验,言语流畅性测验得分均低于正常对照组,差异有统计学意义(P<0.05);(2)认知功能的影响因素:进行多重线性回归分

  3. Neuroprotective effect of therapeutic hypothermia versus standard care alone after convulsive status epilepticus: protocol of the multicentre randomised controlled trial HYBERNATUS.

    Science.gov (United States)

    Legriel, Stephane; Pico, Fernando; Tran-Dinh, Yves-Roger; Lemiale, Virginie; Bedos, Jean-Pierre; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-01

    Convulsive status epilepticus (CSE) is a major medical emergency associated with a 50 % morbidity rate. CSE guidelines have recommended prompt management for many years, but there is no evidence to date that they have significantly improved practices or outcomes. Developing neuroprotective strategies for use after CSE holds promise for diminishing morbidity and mortality rates. Hypothermia has been shown to afford neuroprotection in various health conditions. We therefore designed a trial to determine whether 90-day outcomes in mechanically ventilated patients with CSE requiring management in the intensive care unit (ICU) are improved by early therapeutic hypothermia (32-34 °C) for 24 h with propofol sedation. We are conducting a multicentre, open-label, parallel-group, randomised, controlled trial (HYBERNATUS) of potential neuroprotective effects of therapeutic hypothermia and routine propofol sedation started within 8 h after CSE onset in ICU patients requiring mechanical ventilation. Included patients are allocated to receive therapeutic hypothermia (32-34 °C) plus standard care or standard care alone. We plan to enrol 270 patients in 11 ICUs. An interim analysis is scheduled after the inclusion of 135 patients. The main study objective is to evaluate the effectiveness of therapeutic hypothermia (32-34 °C) for 24 h in diminishing 90-day morbidity and mortality (defined as a Glasgow Outcome Scale score <5). The HYBERNATUS trial is expected to a decreased proportion of patients with a Glasgow Outcome Scale score lower than 5 after CSE requiring ICU admission and mechanical ventilation. Trial registration Clinicaltrials.gov identifier NCT01359332 (registered on 23 May 2011). PMID:27325409

  4. Immediate Epileptogenesis after Kainate-Induced Status Epilepticus in C57BL/6J Mice: Evidence from Long Term Continuous Video-EEG Telemetry.

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    Sreekanth Puttachary

    Full Text Available The C57BL/6J mouse as a model of seizure/epilepsy is challenging due to high mortality and huge variability in response to kainate. We have recently demonstrated that repeated administration of a low dose of kainate by intraperitoneal route can induce severe status epilepticus (SE with 94% survival rate. In the present study, based on continuous video-EEG recording for 4-18 weeks from epidurally implanted electrodes on the cortex, we demonstrate that this method also induces immediate epileptogenesis (<1-5 days post-SE. This finding was based on identification of two types of spontaneous recurrent seizures; behavioral convulsive seizures (CS and electrographic nonconvulsive seizures (NCS. The identification of the spontaneous CS, stage 3-5 types, was based on the behaviors (video that were associated with the EEG characteristics (stage 3-5 epileptiform spikes, the power spectrum, and the activity counts. The electrographic NCS identification was based on the stage 1-2 epileptiform spike clusters on the EEG and their associated power spectrum. Severe SE induced immediate epileptogenesis in all the mice. The maximum numbers of spontaneous CS were observed during the first 4-6 weeks of the SE and they decreased thereafter. Mild SE also induced immediate epileptogenesis in some mice but the CS were less frequent. In both the severe and the mild SE groups, the spontaneous electrographic NCS persisted throughout the 18 weeks observation period, and therefore this could serve as a chronic model for complex seizures. However, unlike rat kainate models, the C57BL/6J mouse kainate model is a unique regressive CS model of epilepsy. Further studies are required to understand the mechanism of recovery from spontaneous CS in this model, which could reveal novel therapeutic targets for epilepsy.

  5. 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

    2016-11-01

    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.

  6. [Complex partial status epilepticus with recurrent episodes of complex visual hallucinations: study by using 123I-IMP-SPECT, brain MRI and EEG].

    Science.gov (United States)

    Sakai, Toshiyuki; Kondo, Masahide; Tomimoto, Hidekazu

    2015-01-01

    We report a 72-year-old woman with complex partial status epilepticus who showed recurrent episodes of complex visual hallucinations (CVH). Brain diffusion-weighted magnetic resonance images revealed gyriform cortical hyperintensity in the right parietal, occipital and temporal lobes, and brain magnetic resonance angiograhy revealed a hyperintensity in the right dilated middle cerebral artery during ictal period. Ictal N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography (123I-IMP-SPECT) with three-dimensional stereotactic surface projection (3D-SSP) 14 days after the onset of the first CVH revealed hyperperfusion in the right latero-inferior occipito-temporal region with relation to motion. CVH spontaneously subsided 17 days after the onset of the first CVH. CVH recurred one year after the first CVH. Ictal 123I-IMP-SPECT with 3D-SSP revealed marked hyperperfusion in the right lateral parietal region probably with relation to face and figure hallucinations. Ictal scalp EEGs revealed rhythmic polyspikes at 12 Hz with high amplitude (100-200 μV) in bilateral posterior occipital and temporal region with the right side dominance for 20 seconds and more in several occasions. Interictal 123I-IMP-SPECT with 3D-SSP 28 days after recurrence of CVH revealed marked hypoperfusion in the right lateral parietal region, and recovery of hypoperfusion in the right latero-inferior occipito-temporal region. These findings suggest that ictal CVH might be induced by the spread of epileptic discharges from the right parieto-occipito-temporal region with the old brain contusion (epileptogenic region) to the right latero-inferior occipito-temporal region and the right lateral parietal region (symptomatogenic regions).

  7. Benign childhood epilepsy with Centro-Temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline--how aggressive should we be?

    Science.gov (United States)

    Uliel-Sibony, Shimrit; Kramer, Uri

    2015-03-01

    Since many of the children with BCECTSs display electrical status epilepticus during sleep and many present with different comorbidities, mainly ADHD and behavioral disturbances, clinicians are often confronted with the dilemma of how aggressive they should be with their efforts of normalizing the EEG. We conducted a retrospective study by screening medical records of all consecutive patients with BCECTSs, spike-wave index (SWI) >30%, and ADHD/ADD that were evaluated in our pediatric epilepsy service and were followed up for at least two years. Patients with neurocognitive deterioration detected by formal testing were excluded. A total of 17 patients with mean age of 6.9years at BCECTS diagnosis were identified. The patients' mean SWI was 60% and that dense electrical activity lasted 1.5years on average (range: 1-4.5years). Six children were formally diagnosed with learning disabilities in addition to ADD/ADHD. All of them were treated with an average of three antiepileptic medications, mainly for the purpose of normalizing the EEG, but none of them was treated with steroids or high-dose diazepam. The mean duration of follow-up was 5.5years. A cognitive or behavioral deterioration was not detected in any of them. Our data suggest that when treating a child with BCECTSs, high SWI, and school difficulties, the most critical parameter that determines the necessity of using second-line antiepileptic agents such as steroids or high-dose diazepam is a formal psychological evaluation that proves cognitive (I.Q.) decline. Otherwise, these agents may be avoided. PMID:25678032

  8. 成人非惊厥性癫(癎)持续状态的临床及脑电图特点%Clinical and electroencephalogram features of nonconvulsive status epilepticus in adults

    Institute of Scientific and Technical Information of China (English)

    余璐; 郑金瓯; 梁志坚; 黄东红

    2011-01-01

    Objective To explore the clinical and electroencephalogram features of nonconvulsive status epilepticus (NCSE) in adults. Methods The clinical data of 7 NCSE patients were retrospective analyzed. Results Complex partial status epilepticus (CPSE) was identified in 6 patients and generalized nonconvulsive status epilepticus was seen in 1 case. The significant clinical presentations were disturbance of consciousness at different levels accompanied with or without clumsy, disorientation, automatism, mental and behavior disorder. Epileptic discharges were seen on electroencephalogram examinations in all patients, and the waveform of epileptic waves had relationship with clinical manifestation. Fine prognosis was induced after treatment according to therapeutic principle of status epilepticus. Conclusions The clinical manifestations are complex in NCSE patients. The electroencephalogram changes are significant, and it probably has some relativity with clinical symptoms and is helpful for diagnosis. Treatment in time will induce fine prognosis.%目的:探讨成人非惊厥性癫癎持续状态(NCSE)的临床及脑电图特点.方法:对7例NCSE患者的临床资料进行回顾性分析.结果:本组7例NCSE患者中,复杂部分性NCSE6例,全面性NCSE1例.临床表现以不同程度意识障碍为主,伴反应迟钝、定向力障碍、自动症、精神行为异常等.脑电图检查均可见癎性发放,且癫癎波形态与临床表现有关.按癫癎持续状态治疗原则治疗后均明显好转.结论:NCSE患者临床表现复杂多样;脑电图改变明显且与临床症状可能有某些相关性,有助于诊断;及时治疗预后良好.

  9. Continuous intravenous infusion of midazolam for treatment of status epilepticus in children%持续静脉滴注咪达唑仑治疗儿童癫癇持续状态

    Institute of Scientific and Technical Information of China (English)

    钟建民; 李建华; 陈勇

    2004-01-01

    @@ 近年来发现咪达唑仑具有抗惊厥作用.2002年7月~2003年3月,我们总结分析了持续静脉滴注咪达唑仑(midazolam)治疗儿童癫癇持续状态(status epilepticus,SE)55例,以探讨其临床应用的有效性和安全性,现报道如下.

  10. 非抽搐性癫痫持续状态五例及文献复习%Non-convulsive status epilepticus: 5 cases report and literature review

    Institute of Scientific and Technical Information of China (English)

    吴春波; 刘晓原; 裴立英; 席晓芳; 杨靓; 刘献增; 朱继红

    2010-01-01

    目的 探讨非抽搐性癫痫持续状态(NCSE)患者的临床表现及持续脑电监测的脑电图(EEG)特征.方法 对自2008年11月至2009年12月北京大学人民医院急诊科收治的5例NCSE患者行持续EEG监测检查,观察其EEG特征及临床表现.结果 5例均出现发作性意识障碍,其中4例出现烦躁、易怒或躁狂,3例表现出精神运动迟滞和遗忘,2例出现言语自动症和失认,1例出现定向障碍.所有患者的EEG均出现广泛性但一侧明显的异常放电.静脉注射地两泮后,3例患者临床症状迅速改善.结论 NCSE并非罕见,持续EEG监测能查出本病,早期诊断,及时治疗可改善患者预后,临床应注意与其他引起意识紊乱的疾病相鉴别.%Objective To describe the clinical and electroencephalographic features as well as the possible etiology and treatment of patients with non-convulsive status epilepticus (NCSE). Methods We identified 5 adult patients with NCSE from the epilepsy database of the comprehensive epilepsy. Continuous electroencephalographic (EEG) monitoring was analyzed and chart review was performed to analyze their clinical and electroencephalographic features. Results The patients ranged from 19 to 66 years old. All of the 5 patients showed impaired consciousness: 4 demonstrated agitation and paranoia; 3 had both psychomotor retardation and amnesia; 2 developed verbal automatisms and agnosia; and 1 had disorientation. All the patients had associated generalized discharges but lateralized dominant. Three patients showed clinical improvement following administration of benzodiazepines. Conclusion The NCSE is not a rare case and continuous EEG monitoring can help the diagnosis. Prompt recognition and treatment may be necessary in improving the neurological outcome, and attention should be paid to the identification with other diseases that cause impairment of conscience.

  11. P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus

    Directory of Open Access Journals (Sweden)

    Ryu Hea Jin

    2011-06-01

    Full Text Available Abstract Background The release of tumor necrosis factor-α (TNF-α appears depend on the P2X7 receptor, a purinergic receptor. In the present study, we addressed the question of whether P2X7 receptor-mediated TNF-α regulation is involved in pathogenesis and outcome of status epilepticus (SE. Methods SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, 2',3'-O-(4-benzoylbenzoyl-adenosine 5'-triphosphate (BzATP, adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP, A-438079, or A-740003 prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunit phosphorylations. Results Following SE, P2X7 receptor agonist (BzATP infusion increased TNF-α immunoreactivity in dentate granule cells as compared with that in saline-infused animals. In addition, TNF-α immunoreactivity was readily apparent in the mossy fibers, while TNF-α immunoreactivity in CA1-3 pyramidal cells was unaltered. However, P2X7 receptor antagonist (OxATP-, A-438079, and A-740003 infusion reduced SE-induced TNF-α expression in dentate granule cells. In the CA3 region, BzATP infusion attenuated SE-induced neuronal damage, accompanied by enhancement of p65-Ser276 and p65-Ser311 NF-κB subunit phosphorylations. In contrast, OxATP-, A-438079, and A-740003 infusions increased SE-induced neuronal death. Soluble TNF p55 receptor (sTNFp55R, and cotreatment with BzATP and sTNFp55R infusion also increased SE-induced neuronal damage in CA3 region. However, OxATP-, sTNFp55R or BzATP+sTNFp55R infusions could not exacerbate SE-induced neuronal damages in the dentate gyrus and the CA1 region, as compared to BzATP infusion. Conclusions These findings suggest that TNF-α induction by P2X7 receptor activation may ameliorate SE-induced CA3 neuronal damage via enhancing NF-κB p65-Ser276 and p65-Ser311 phosphorylations.

  12. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

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    Ruohonen Saku

    2011-04-01

    Full Text Available Abstract Background Status epilepticus (SE is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. Methods SE was induced by an intraperitoneal (i.p. injection of kainic acid (KA in 9- and 21-day-old (P9 and P21 rats. The mRNA expression of interleukin-1 beta (IL-1β, tumor necrosis factor-alpha (TNF-α, interleukin-10 (IL-10, matrix metalloproteinase-9 (MMP-9, glial-derived neurotrophic factor (GDNF, interferon gamma (IFN-γ, and transforming growth factor-beta 1 (TGF-β1 were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR. IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. Results SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Conclusion Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the

  13. Effect of penequinine hydrochloride on the expression of RAGE in rat hippocampal neurons after status epilepticus%盐酸戊乙奎醚对癫疒间持续状态大鼠海马神经元RAGE表达的影响

    Institute of Scientific and Technical Information of China (English)

    程伟; 朱建南; 孙秀媛; 齐敦益; 戴体俊; 刘功俭

    2012-01-01

    Objective To investigate the effect of penequinine hydrochloride on the expression of RAGE and NF -κB in rat hippocampal neurons after status epilepticus . Methods Male SD rats were randomly divided into three groups , ie. A control group, a status epilepticus group and a penequinine hydrochloride group (re = 8 each). The rats abdominal cavity of status epilepticus group were injected lithium - pilecarpine to establish status epilepticus model. The expression of RAGE and nuclear factor kappa B ( NF - κB) p65 in hippocampal was measured by Western blot. TUNEL assay was used merely to identify apoptotic cells. Results Compared with the control group , the expression of RAGE and NF - κB p65 was significantly higher in status epilepticus group and apoptotic cells were significant increased (P <0.01). Compared with the status epilepticus group , the expression of RAGE and NF - κB p65 was significantly lower and apoptotic cells were decreased in penequinine hydrochloride group ( P < 0. 01). Conclusion Penequinine hydrochloride shows a protective effects on rat hippocampal neurons after status epilepticus through inhibiting the expression of RAGE and NF -κB.%目的 探讨盐酸戊乙奎醚(长托宁)对癫(癎)持续状态(SE)后大鼠海马晚期糖基化终末产物受体(RAGE)和核因子κB(NF-κB)的影响.方法 SD大鼠随机分为A组(对照组)、B组(模型组)和C组(盐酸戊乙奎醚组),每组8只.应用氯化锂-匹罗卡品制备SE模型.TUNEL法检测大鼠海马细胞凋亡,Western blot法检测大鼠海马RAGE及NF-κB p65的表达改变情况.结果 与A组比较,B组大鼠海马RAGE、NF-κB p65水平明显增高,神经元凋亡增加(P<0.01);与B组比较,C组大鼠海马RAGE、NF-κB p65水平降低,神经元凋亡减少(P<0.01).结论 盐酸戊乙奎醚可抑制RAGE-NF-κB通路和减少神经元凋亡,对SE后大鼠海马神经元发挥保护作用.

  14. 癫(痫)持续状态模型中海马神经元损伤及其可能机制%Hippocampal neuronal damage and its possible mechanism in status epilepticus

    Institute of Scientific and Technical Information of China (English)

    丁秀芳; 王纪文; 姚国; 代方方; 张冰

    2015-01-01

    目的探讨癫(痫)持续状态(SE)大鼠模型中海马神经元损伤、谷氨酸α-氨基-3-羟基-5-甲基异(噁)唑-4-丙酸(AMPA)受体第二亚单位GluR2的表达变化以及是否存在GluR2与甘油醛-3-磷酸脱氢酶(GAPDH)蛋白复合物的耦合变化.方法 应用氯化锂-毛果芸香碱建立SE大鼠模型(62只),同时设立正常对照组(20只),按照随机数字表法将建SE大鼠分为SE后1h组(6只)、6h组(12只)、24h组(12只)、72 h组(12只)及7d组(20只).按照随机数字表法选择正常对照及SE后6h、24 h、72 h、7d(各6只)作Nissl染色、原位末端标记(TUNEL)分别观察大鼠海马形态学变化、凋亡发生;再选择对照组及SE后1h、6h、24 h、72 h及7d组大鼠(各6只)用Western blot检测GluR2蛋白的表达变化,用免疫共沉淀及Western blot技术研究GluR2与GAPDH蛋白复合物的耦合变化情况.结果 SE后各时间点海马CA1、CA3区神经细胞数量显著减少,与正常对照组比较差异有统计学意义(F=30.866、24.043,P均<0.05);SE后24h、72 h、7d海马CA1、CA3区凋亡细胞数量增加,与正常对照组比较差异有统计学意义(F=84.762、52.574,P均<0.01);与正常对照组比较,SE后1h、6h海马GluR2蛋白相对表达量减少,但差异无统计学意义(P>0.05),SE后24 h、72 h、7 d GluR2相对表达量减少,差异有统计学意义(F=76.506,P<0.01);SE后72 h与正常对照组比较,GluR2与GAPDH形成的蛋白复合物耦合增加,差异有统计学意义(t=7.029,P<0.05).结论 SE可导致海马区神经元损伤,GluR2表达降低及GluR2/GAPDH蛋白复合物耦合增加可能是其机制之一.%Objective To investigate hippocampal neuronal damage and dynamic change of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR2 in status epilepticus, to find out whether GluR2/glyceral dehyde-3-phosphate dehydrogenase (GAPDH) interaction has any change.Methods Male Wistar rats (62 cases) were induced to status epilepticus

  15. Lovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results Lovastatina reduz a lesão celular na região CA1 do hipocampo após o status epilepticus induzido pela pilocarpina: resultados preliminares

    Directory of Open Access Journals (Sweden)

    Pauline Rangel

    2005-12-01

    Full Text Available OBJECTIVE: To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE METHOD: Adult male Wistar rats were divided into four groups: (A control rats, received neither pilocarpine nor lovastatin (n=5; (B control rats, received just lovastatin (n=5; (C rats that received just pilocarpine (n=5; (D rats that received pilocarpine and lovastatin (n=5. After pilocarpine injection (350mg/kg, i.p., only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p. after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method. RESULTS: The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1= 26.8 ± 13.67; CA3= 38.1 ± 7.2; hilus= 43.8 ± 3.95 when compared with control group animals (Group A: CA1= 53.2 ± 9.63; CA3= 63.5 ± 13.35; hilus= 59.08 ± 10.24; Group B: CA1= 74.3 ± 8.16; CA3= 70.1 ± 3.83; hilus= 70.6 ± 5.10. The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 ± 17.88 was statically significant increased when compared with animals that just presented SE. CONCLUSION: Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.OBJETIVO: Capacidade da lovastatina em prevenir a perda de neurônios hipocampais após o status epilepticus (SE induzido pela pilocarpina. MÉTODO: Ratos adultos Wistar foram divididos em 4 grupos: (A ratos controles que não receberam pilocarpina nem lovastatina (n=5; (B ratos

  16. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    Science.gov (United States)

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    Summary Purpose sec-Butyl-propylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a CNS-active amide derivative of valproic acid (VPA) currently in phase II clinical trials. The current study evaluated the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy models and assessed its efficacy in rat and guinea pig models of status epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of excitotoxic cell death. Methods SPD’s anticonvulsant activity was evaluated in several rodent seizure and epilepsy models including: maximal electroshock (MES), 6Hz psychomotor, subcutaneous (s.c.) metrazol-, s.c., picrotoxin, s.c. bicuculline, audiogenic and corneal and hippocampal kindled seizures following intraperitoneal administration. Results obtained with SPD are discussed in relationship to those obtained with VPA and VCD. SPD was also evaluated for its ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and soman (rats and guinea pigs) following intraperitoneal administration. SPD was tested for its ability to block excitotoxic cell death induced by the glutamate agonists N-methyl-D-Aspartate (NMDA) and kainic acid (KA) using organotypic hippocampal slices and SE-induced hippocampal cell death using FluoroJade B staining. The cognitive function of SPD-treated rats that were protected against pilocarpine-induced convulsive SE was examined 10-14 days post SE using the Morris water maze (MWM). The relationship between the pharmacokinetic profile of SPD and its efficacy against soman-induced SE was evaluated in two parallel studies following SPD (60 mg/kg, i.p.) administration in the soman SE rat model. Key Findings SPD was highly effective and displayed a wide protective index (PI=TD50/ED50) in the standardized seizure and epilepsy models employed. SPD’s wide PI values demonstrate that it is effective at doses well below those that produce behavioral impairment. Unlike VCD, SPD also

  17. 地西泮与丙戊酸钠治疗癫痫持续状态的疗效比较%Comparison of effects of diazepam and sodium valproate on status epilepticus

    Institute of Scientific and Technical Information of China (English)

    孙洲; 王磊; 龚瑜; 孙圣刚; 苏颖; 梁直厚

    2011-01-01

    Objective:To explore the effects of diazepam and sodium valproate injection in treating status epilepticus (SE). Method:Thirty five adult patients with status epilepticus were observed. In diazepam group (sixteen patients), diazepam was given by intravenous injection at 10 mg with 2 mg·min-1, then diazepam 50 mg plus 0.90% sodium chloride injection 500 ml was given continuously by intravenous drip, and the total quantity is no more than 120 mg in 24 h. In sodium valproate group (nineteen patients), sodium valproate injection 400 mg was administered by intravenous, then sodium valproate 400 mg injection plus 0.9 % sodium chloride injection 50 ml was pumped by intravenous, and the total quantity was no more than 20~30 mg·kg-1 in 24 h. Result:There was no significant difference between diazepam group and sodium valproate group in treating status epilepticus on effective rate, control time and 48 h recurrence rate. Conclusion:The difference of effect between diazepam and sodium valproate in treating status epilepticus was no significant.%目的:回顾性比较丙戊酸钠注射液与地西泮治疗癫痫持续状态的疗效.方法:选择我院神经内科近两年来收治的成人癫痫持续状态患者35例.地西泮组16例入院后立即予地西泮10 mg以2 mg·min-1静脉缓慢注射,注射完毕后给予地西泮50 mg加0.9%氯化钠注射液500 ml静脉缓慢滴注维持,24 h总量不超过120 mg;丙戊酸钠组19例入院后立即予丙戊酸钠注射液400 mg静脉注射,注射完毕后给予丙戊酸钠400 mg加0.9%氯化钠注射液50 ml静脉微泵缓慢注射维持,24 h总量不超过20~30 mg·kg-1.结果:两组抽搐控制率、抽搐控制时间、48 h内复发率比较均差异无统计学意义.结论:丙戊酸钠注射液与地西泮在治疗癫痫持续状态疗效方面无明显差别.

  18. 重症脑疾病患者非惊厥性癫痫持续状态研究进展%Research progress of nonconvulsive status epilepticus in severe brain diseases

    Institute of Scientific and Technical Information of China (English)

    汪叶松; 邓艳春

    2010-01-01

    @@ 非惊厥性癫痫持续状态(nonconvulsive status epilepticus,NCSE)是癫痫传统分类中的一大类,虽然在新的癫痫国际分类中较少提及,但在临床上,特别是在重症患者中的应用却较广泛,其诊治是现代神经病学中一个极大的挑战[1~3].癫痫发作及其持续状态在重症疾病的患者中很常见,尤其是重症脑疾病和有严重的神经系统并发症患者.Z

  19. 老年期全面惊厥性癫持续状态预后不良的影响因素%To Explore the Influence Factors of senile Comprehensive Convulsive status Epilepticus of poor Prognosis

    Institute of Scientific and Technical Information of China (English)

    单玉民

    2015-01-01

    目的:探讨老年期全面惊厥性癫持续状态预后不良的影响因素。方法对2013年6月至2014年6月我院收治的60例全面惊厥性癫患者资料进行回顾性分析。结果60例患者中病死7例,占11.7%,均死于多器官功能障碍综合征(MODS);53例生存患者中,32例出现不同程度的复发,21例得到完全控制,复发率为53.3%,治愈率为35.0%。结论老年期全面惊厥性癫持续状态预后不良的影响因素有MODS、原发病未根除以及机体的自身因素等。%Objective To explore the influence factors of senile comprehensive convulsive status epilepticus of poor prognosis.Methods In 2013 June to 2014 June in our hospital 60 cases of epilepsy patients comprehensive retrospective analysis..Results 7 patients died,60 death patients accounted for 11.7%,al died of multiple organ failure comprehensive disorder syndrome multiple organ(MODS);53 cases of survivors,32 cases occurred different degrees of recurrence,21 cases got complete control,the cure rate was 35.0%,the recurrence rate was 53.3%. Conclusion The influence factors of senile comprehensive convulsive status epilepticus of poor prognosis of MODS,the primary disease was not eradicated and the body's own factors etc.

  20. (R-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Lammertsma Adriaan A

    2011-01-01

    Full Text Available Abstract Background Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp expression and functionality at an early stage after induction of status epilepticus by kainate. Methods (R-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles as well as by population mixed effects modelling (NONMEM. Results All data analysis approaches indicated only modest differences in brain distribution of (R-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. Conclusions P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

  1. Neuropsychological indication and treatment for electrical status epilepticus during sleep in children%儿童睡眠中癫癎性电持续状态的神经心理指征及治疗

    Institute of Scientific and Technical Information of China (English)

    张双

    2004-01-01

    @@ 1971年,Patry和Tassinari首先报道了睡眠中癫(疒间)性电持续状态(electrical status epilepticus during sleep,ESES)并提出了诊断标准,即非快动眼(NREM)睡眠期持续广泛的棘慢波发放占整个NREM期的85%以上.指出ESES作为一种特殊的脑电图现象与认知和语言障碍、癫(疒间)发作相关.随后研究发现ESES虽然仅占癫(疒间)患儿的0.5%,但神经心理学方面的损伤非常突出,越来越引起大家的重视.近年来对易于发生ESES的癫(疒间)综合征,ESES神经心理损伤的特点,以及治疗反应均进行了相当多的研究,现就研究进展作以下总结.

  2. Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Akifumi [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)], E-mail: yamaaki@sahs.med.osaka-u.ac.jp; Momosaki, Sotaro; Hosoi, Rie [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Abe, Kohji [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan); Developmental Research Laboratories, Shionogi and Co., Ltd., Toyonaka, Osaka, 561-0825 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Johnan, Fukuoka 814-0180 (Japan); Inoue, Osamu [Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871 (Japan)

    2009-11-15

    Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [{sup 14}C]2-deoxyglucose ([{sup 14}C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [{sup 14}C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [{sup 14}C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [{sup 14}C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.

  3. Clinical analysis of 4 cases of childhood Rolandic epilepsy with electrical status epilepticus during sleep%儿童Rolandic癫癎伴睡眠期癫癎性电持续状态4例临床分析

    Institute of Scientific and Technical Information of China (English)

    束晓梅; 张贵萍; 杨冰竹; 李磊

    2011-01-01

    @@ 儿童Rolandic癫癎又称儿童良性癫癎伴中央颞区棘波(benign childhood epilepsy with centrotemporal spikes, BECT),是一种特发性局灶性年龄依赖性癫癎,为儿童期最常见的癫癎综合征之一,不伴有认知障碍,预后良好.近年来,研究显示不少的BECT为非典型表现,类型较多,包括睡眠期癫癎性电持续状态(electrical status epilepticus during sleep,ESES)、Landau-Kleffner综合征及伴有不典型失神、失张力或肌阵挛等发作形式的BECT.本研究将病程中伴有ESES的4例不典型BECT患儿进行随访研究,分析其临床特点、脑电图特点及疗效.

  4. Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy.

    Science.gov (United States)

    Löscher, Wolfgang

    2002-06-01

    Control of epilepsy has primarily focused on suppressing seizure activity by antiepileptic drugs (AEDs) after epilepsy has developed. AEDs have greatly improved the lives of people with epilepsy. However, the belief that AEDs, in addition to suppressing seizures, alter the underlying epileptogenic process and, in doing so, the course of the disease and its prognosis, is not supported by the current clinical and experimental data. An intriguing possibility is to control acquired epilepsy by preventing epileptogenesis, the process by which the brain becomes epileptic. A number of AEDs have been evaluated in clinical trials to test whether they prevent epileptogenesis in humans, but to date no drug has been shown to be effective in such trials. Thus, there is a pressing need for drugs that are truly antiepileptogenic to either prevent epilepsy or alter its natural course. For this purpose, animal models of epilepsy are an important prerequisite. There are various animal models with chronic brain dysfunctions thought to reflect the processes underlying human epilepsy. Such chronic models of epilepsy include the kindling model of temporal lobe epilepsy (TLE), post-status models of TLE in which epilepsy develops after a sustained status epilepticus, and genetic models of different types of epilepsy. Currently, the kindling model and post-status models, such as the pilocarpine or kainate models, are the most widely used models for studies on epileptogenic processes and on drug targets by which epilepsy can be prevented or modified. Furthermore, the seizures in these models can be used for testing of antiepileptic drug effects. A comparison of the pharmacology of chronic models with models of acute (reactive or provoked) seizures in previously healthy (non-epileptic) animals, such as the maximal electroshock seizure test, demonstrates that drug testing in chronic models of epilepsy yields data which are more predictive of clinical efficacy and adverse effects, so that

  5. EEG Diagnosis and Clinical Treatment of Electrical Status Epilepticus during Sleep%睡眠中癫痫性电持续状态的脑电诊断及临床治疗

    Institute of Scientific and Technical Information of China (English)

    曹晓春; 刘希娟; 丁勇民; 宋小华; 刘燕玲; 叶春风; 李国林; 刘洋; 龚丹

    2015-01-01

    目的:探讨睡眠中癫痫性电持续状态(electrical status epilepticus during sleep,ESES)的脑电诊断及临床治疗。方法脑电图棘慢波指数(SWI)≥50%并完成治疗的癫痫患儿30例(A 组16例:50%≤SWI<85%;B 组14例:SWI≥85%),按就诊顺序随机分为 C、D 2组,每组15例,行不同疗程(C 组6个月,D 组12个月)激素治疗,治疗前后均进行神经心理损伤评估,并随访治疗后的疗效及不良反应。结果A、B 2组治疗前均有程度不一的神经心理损伤,言语智商(VIQ)、操作智商(PIQ)及总智商(FIQ)均较正常值低,以 VIQ 下降最显著,B 组 VIQ 和 FIQ较 A 组低,差异有统计学意义(P <0.05);C、D 组 VIQ、FIQ 较激素治疗前均有增高(P <0.05),其中 ESES 消失者VIQ、FIQ 明显高于治疗前(P <0.05),但 C、D 2组间神经心理损伤改善程度及总有效率比较差异无统计学意义(P >0.05);D 组不良反应大于 C 组(P <0.05)。结论SWI≥50%定为 ESES 的脑电诊断标准有助于 ESES 的合理诊断,早期干预;激素治疗 ESES 安全有效,疗程6个月更合理。%ABSTRACT:Objective To investigate the EEG diagnosis and clinical treatment of electrical sta-tus epilepticus during sleep(ESES).Methods According to the spike-wave index(SWI),30 chil-dren with epilepsy were divided into group A(50% ≤ SWI0.05).Conclusion The criterion of SWI≥50%contributes to the reasonable diagnosis and early intervention of ESES.Hormone treatment for 6 months is effective and reasonable for ESES.

  6. Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus

    Directory of Open Access Journals (Sweden)

    Kim Ji-Eun

    2012-01-01

    Full Text Available Abstract Background Status epilepticus (SE induces severe vasogenic edema in the piriform cortex (PC accompanied by neuronal and astroglial damages. To elucidate the mechanism of SE-induced vasogenic edema, we investigated the roles of tumor necrosis factor (TNF-α in blood-brain barrier (BBB disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced SE. Methods SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, and soluble TNF p55 receptor (sTNFp55R prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunits. Results Following SE, most activated microglia showed strong TNF-α immunoreactivity. In addition, TNF p75 receptor expression was detected in endothelial cells as well as astrocytes. In addition, only p65-Thr435 phosphorylation was increased in endothelial cells accompanied by SMI-71 expression (an endothelial barrier antigen. Neutralization of TNF-α by soluble TNF p55 receptor (sTNFp55R infusion attenuated SE-induced vasogenic edema and neuronal damages via inhibition of p65-Thr435 phosphorylation in endothelial cells. Furthermore, sTNFp55R infusion reduced SE-induced neutrophil infiltration in the PC. Conclusion These findings suggest that impairments of endothelial cell functions via TNF-α-mediated p65-Thr 485 NF-κB phosphorylation may be involved in SE-induced vasogenic edema. Subsequently, vasogenic edema results in extensive neutrophil infiltration and neuronal-astroglial loss.

  7. Epileptic nystagmus as a prominent symptom in status epilepticus: a report of 3 cases%以癫痫性眼震为主的癫痫持续状态三例报道

    Institute of Scientific and Technical Information of China (English)

    王丽英; 王政伟; 岳云龙; 刘文宏

    2014-01-01

    Objective To analyze the typical clinical and imaging characteristics of epileptic nystagmus (EN) to provide a reference for better diagnosis and treatment of EN.Methods Three patients with EN,admitted to our hospital from 2008 to 2010,were chosen; the clinical presentations and ictal epileptiform discharges by magnetic resonance imaging (MRI) or transcranial cerebral Doppler (TCD) were studied retrospectively.Results All patients showed a binocular syntropy horizontal nystagmus and conjugate eye deviation on onset.Among all the three,two had head deviation,one visual hallucination and one vertigo; during onset,altered mental state and/or impaired consciousness were noted.The ictal EEG revealed that the 11-14 Hz spike waves mainly originated from the temporal-parietal-occipital border area was opposed to the direction of the nystagrnus (one left and two right).Diffusion-weighted imaging (DWI) abnormal high signal and high signal of fluid-attenuated inversion recovery sequences were located at left parietal-occipital region (n=1),right temporal-parietal-occipital region (n=1) and right occipital-temporal region (n=1) in the 1.5 T MRI.TCD indicated an elevated flow velocity in the ipsilateral middle/posterior cerebral artery during status epilepticus.Conclusions The epileptic nystagrnus as a prominent symptom in status epilepticus is a rare type of status epilepticus.Video-EEG is the key method in the diagnosis of the disease.The direction of the nystagrnus usually is contralateral to the brain lesion and/or the ictal discharges.The frequent seizures induce DWI abnormality.Epileptogenic zone is localized to the temporal-parietal-occipital region.%目的 归纳总结癫痫性眼震的临床表现及影像学特点,为临床工作者更好地识别本病提供参考. 方法 回顾性分析北京世纪坛医院功能神经外科自2008年至2010年收治的3例以癫痫性眼震为主要症状的癫痫持续状态患者的临床资料,结合文

  8. Absence status seen in an adult patient

    Directory of Open Access Journals (Sweden)

    Hasan H Ozdemir

    2013-01-01

    Full Text Available Absence status epilepticus (ASE is a type of nonconvulsive status epilepticus in which continuous or recurrent generalized epileptiform discharges are associated with a varying grade of consciousness impairment. Absence status epilepticus may be obtained during progress of many epileptic syndromes, in several metabolic disturbances and related to use of several drugs. Absence status epilepticus is generally seen in childhood; rarely it can be seen in adulthood. In this paper, the case which has never diagnosed until now in spite of many absence seizures for years, applied for absence seizures to our clinic and diagnosed for juvenile absence epilepsy, has been discussed.

  9. Pilocarpine诱导小鼠癫痫持续状态发作后海马神经元的兴奋激活、损伤和死亡%Neuron activation, degeneration and death in the hippocampus of mice after pilocarpine induced status epilepticus

    Institute of Scientific and Technical Information of China (English)

    刘建新; 唐锋儒; 刘勇

    2011-01-01

    目的:研究癫痫持续状态发作后海马神经元兴奋激活、细胞损伤和细胞死亡的发生和相互关系.方法:采用pilocarpine诱导Swiss小鼠癫痫持续状态(status epilepticus,SE)模型,分别以c-Fos,Fluoro Jade B和CFV染色分析SE后不同时间点齿状回和CA1区锥体细胞的兴奋激活、损伤和细胞存活状况.结果:在齿状回颗粒细胞层,c-Fos阳性细胞在SE后1,2和24 h增多(P<0.01或0.05),但各组齿状回颗粒细胞层均无明显Fluoro Jade B阳性细胞,CFV染色标记的阳性细胞数量在对照组和各实验组之间差异无统计学意义(P>0.05);门区神经元在SE后没有明显的c-Fos诱导表达,但SE后2和24 h,门区Fluoro Jade B阳性细胞数量较对照组增多(P<0.01),CFV染色显示SE后1d门区残存的神经元数量较对照组减少(P<0.01);CA1区锥体细胞层c-Fos阳性细胞数量在SE后30 min,1,2和24 h后增多(P<0.01或0.05),Fluoro Jade B 阳性细胞数量在SE后2和24 h也较对照组增多(P<0.01),但CFV染色CA1区锥体细胞数量在各组间差异无统计学意义(P>0.05).结论:齿状回颗粒细胞、门区中间神经元以及CA1区锥体细胞在SE后的兴奋激活、颗粒细胞的损伤和死亡之间无直接的必然关系.%Objective To examine the occurrence of neuron activation,neurodegeneraion and cell death,and the correlation among them in the hippocampus after status epilepticus.Methods CFV,Fluoro Jade B and c-Fos staining were done at multiple time points after pilocarpine induced status epilepticus.Results In the stratum granulosum of dentate gyrus,c-Fos positive neurons increased significantly at 1 h,2 h and 1 d after status epilepticus (P <0.01 or 0.05).However,almost no Fluoro Jade B staining cell was found in the stratum granulosum in the experiment and control groups,and no obvious difference was shown on the numbers of CFV staining cells in this area among all groups.In the hilus of dentate gyrus of different groups

  10. 中老年复杂部分性发作癫痫持续状态的临床特征及误诊分析%Complex partial status epilepticus in the elderly: clinical features and causes of misdiagnosis

    Institute of Scientific and Technical Information of China (English)

    刘晓蓉; 宋兴旺; 常好会; 王玉良; 邹欣

    2009-01-01

    Objective To investigate the clinical features and causes of misdiagnosis of complex partial status epilepticus (CPSE) in the elderly. Methods The clinical data of elderly patients with CPSE admitted in our department between January and December, 2008 with previous misdiagnosis were reviewed. The diagnosis of CPSE was established according to the diagnostic criteria of the International League Against Epilepsy (ILAE). All the patients underwent video-EEG examination, head magnetic resonance imaging (MRI), and routine biochemical examination, and were followed up for at least 3 months. Results Seven female CPSE patients were involved in this analysis including 2 with frontal lobe epilepsy and 5 with temporal lobe epilepsy. The conditions were misdiagnosed as a variety of diseases including Alzheimer's disease, cerebral infarction, coronary heart disease, encephalitis, hysterism, and schizophrenia, and the duration of the misdiagnoses ranged from 2 days to 40 years. Video-EEG showed slow background, continuous interictal discharges or high-voltage slow waves in the temporal or frontal lobe, or ictal discharges of complex partial seizures. After treatment with antiepileptic medications, 3 patients were free of epileptic episodes within 3 months, 3 still remained in complex partial status, and 1 had repeated CPSE. Conclusions Complex symptoms, atypical EEG, co-morbidity and social factors all contribute to misdiagnosis of CPSE in the elderly. Suspected patients should undergo video-EEG examination for a definite diagnosis as early as possible.%目的 分析中老年复杂部分性发作癫痫持续状态(CPSE)的临床特点及误诊原因.方法 收集广州医学院第二附属医院神经内科自2008年1月至12月收治、曾被外院误诊的中老年CPSE患者的临床资料,进行视频脑电图(EEG)、头颅MR、生化检查,根据国际抗癫痫联盟的CPSE诊断标准进行诊断,并随访3个月以上. 结果 本组患者7例,均

  11. Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Rivelilson Mendes de Freitas

    2003-06-01

    Full Text Available Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.. Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.. Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and

  12. Behandlingsrefraktaert status epilepticus med letal rabdomyolyse

    DEFF Research Database (Denmark)

    Kreft, Andreas; Rasmussen, Niels; Hansen, Lars Kjaersgård

    2008-01-01

    We are reporting two cases of SE with lethal rhabdomyolysis. Both were treated according to the guidelines on antiepileptic drug management by the Danish Paediatric Society, with one and two hours' delay, respectively. Intubation and midazolam infusion were needed to control seizures. After appro...

  13. 左乙拉西坦对儿童睡眠中癫癎性电持续状态的影响%Therapeutic effects of levetiracetam on electrical status epilepticus during sleep in children

    Institute of Scientific and Technical Information of China (English)

    张玮娜; 邹丽萍; 鞠俊; 李晓燕

    2012-01-01

    Objective To study the efficacy of levetiracetatn (LEV) in the treatment of electrical status epilepticus during sleep ( ESES) in children. Methods The clinical data of 27 children who were newly diagnosed with ESES and treated with LEV between August 2009 and March 2011 and who were followed up for at least 6 months were retrospectively studied. Results The onset age of the 27 children ranged from 9 months to 9 years and 7 months. Partial motion seizures were found in 81% of the children in the early stage. Twenty-three children received LEV treatment after ESES was definitely diagnosed. Of the 23 children, 19 were diagnosed as epilepsy syndrome of benign childhood epilepsy with centrotemporal spikes ( BECT). The age of the patients at the beginning of LEV treatment ranged from 1 year and 8 months to 11 years and 9 months. The follow- up duration was 7 to 19 months. The effective rate of LEV for seizure control was 82% and for EEG recovery it was 78% (P < 0.05). The other 4 children received LEV treatment before the occurrence of ESES. Seizure control and EEG recovery were noted in two of the 4 children. Conclusions LEV treatment is efficacious, to some extent, for both seizure control and EEG recovery in children with ESES.%目的 探讨左乙拉西坦(levetiracetam,LEV)治疗儿童睡眠中癫癎性电持续状态(ESES)的疗效.方法 对2009年8月至2011年3月首诊的27例ESES患儿使用LEV状况进行分析,并最少随访6个月.结果 27例ESES患儿起病年龄为9个月至9岁7个月,起病早期81%的患儿为局限性运动发作.23例为ESES确诊后加用LEV治疗,其中19例为良性癫癎伴中央颞区棘波(BECT)患儿,4例为非BECT的ESES患儿.LEV开始治疗年龄为l岁8个月至11岁9个月,随访时间为7~19个月.LEV控制发作有效率为82%,改善脑电图(EEG)情况有效率为78%.LEV控制临床发作效果优于改善EEG效果(P<0.05).另4例患儿于ESES前已加用LEV治疗,其中2例临床发作得到控

  14. The clinical features and prognosis of nonconvulsive status epilepticus in children: analysis of 12 cases%儿童非惊厥性癫痫持续状态12例临床特征与预后分析

    Institute of Scientific and Technical Information of China (English)

    朱丽萍; 席加水; 王学禹; 聂翠丽

    2012-01-01

    Objective To study the clinical and EEC features. therapeutic response and prognosis of nonconvulsive status epilepticus (NCSE)in children.Methods The clinical and EEG data of 12 children with NCSE were analyzed and therapeutic response and prognosis were followed up. Results The median onset age of symptoms was(6.22.72)yeais. The median duration of seizures was 35h. There were 3 children with absence status epilepsy (ASE)and 9 with psychomo-tor status epilepsy (PSE). The clinical presentations of NCSE included impairment of consciousness(n=12) .speech deterioration (n=9), behavior change (n=8), subtle motor findings such as eyelid twitching(n=5), illusion(n=2) , eating more food than ever or thirsty(n=2), and vegetative manifestation(n=l). The ictal EEG of NCSE showed slow activity with generalized spike-and-slow wave discharges and slow waves(n=3), and continuous or periodic focal discharges(n= 9), which was predominant with 9 or 5 activity(n=5), spike-and-slow wave discharges (n=4) .discharges in temporal region (n=3), out of temporal region (n=2) and temporal with other regions (n=4) .The control ratio of intravenous diazepam between ASE and PSE had no statistically significant difference(P > 0.05).Six children had cognitive impairment.Conclusion The main manifestations of NCSE are consciousness, speech deterioration and behavior change.The diagnosis can be made by ictal EEG.The prompt and effective manipulation of NCSE may reduce cognitive impairment.%目的 探讨儿童非惊厥性癫痫持续状态(NCSE)的临床表现、脑电图(EEG)特征、治疗及预后,提高诊疗水平.方法 对2005年1月至2011年4月山东大学附属省立医院小儿神经科病房收治的12例NCSE患儿临床及EEG资料进行分析,并随访治疗疗效及预后.结果 12例中男8例、女4例,平均起病年龄(6.22±3.72)岁,发作持续时间平均为35h,失神癫痫持续状态(ASE)3例,精神运动性癫痫持续状态(PSE)9例.其中意识障碍12

  15. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus)

    OpenAIRE

    Buckmaster, Paul S.; Wen, Xiling; TOYODA, Izumi; Gulland, Frances M. D.; Van Bonn, William

    2014-01-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Ni...

  16. Hippocampal neurogenesis in developing rats induced by status epilepticus%癫痫持续状态诱导发育幼鼠海马神经的发生

    Institute of Scientific and Technical Information of China (English)

    袁宝强; 袁婷婷; 周保健; 张冬丽; 崔湘君; 李凡; 樊秋萍

    2012-01-01

    Objective To observe neural stem cells proliferation,migration and differentiation in hippocampus in developing rats with status epileptictus.Methods 320 healthy SD rats at age 7,14,21,28 d (P7,P14,P21,P28) were randomly divided into status epilepticus (SE) and normal control group.In each group those rats at the same age were further randomly divided into 1,7,14,21,28 d five time points after PTZ-induced SE (n =8).New cell proliferation and migration were observed by immunohistochemistry studies in the dentate gyms.Double labeling with Brdu/NeuN and Brdu/GFAP was performed in the P14 rats.Results Nestin positive cells appeared in the dentate gyms on 1 d after SE in P7,P14,P21,P28 rats.The number of nestin positive cells gradually increased on 7 d and reached a peak on 14 d,then gradually reduced on 21 d,finally fell to a minimum on 28 d after SE.The numbers of nestin positive cells on 7 d(177.00 ± 3.22,t =16.033) and 14 d (195.00 ± 3.41,t =28.840) were significantly higher in the SE group than the NS group (147.50 ± 2.08,136.50 ± 2.65,both P < 0.05).The smaller age of rats with SE onset,the greater the nestin intensity.But the number of nestin positive cells in the dentate gyrus of normal rats were gradually decreased with increasing age.Nestin positive cells were distributed in subgranular zone of dentate gyrus on 1 d and 7 d after SE,then gradually migrated to the granule cell layer on 14 d with morphological changes.Small part of nestin positive cells were ectopically migrated to the hilus of dentate gyrus in P14,P21,P28 age rats,and were also seen in the CA1,CA3 of hippocampus and cortex with various cell morphology.For differentiation of newly generated cells,most of Brdu positive cells coexpressed NeuN and about 4%-5% cells co-expressed GFAP.Conclusions SE could induce neurogenesis in the hippocampal dentate gyrus area in developing rats which has age-related characteristics.Most new cells migrate from the subgranular zone to the granule cell layer

  17. Establishment of post-status epilepticus model of temporal lobe epilepsy induced by electrical stimulation of the amygdala in rats and spontaneous recurrent seizures%大鼠杏仁核电刺激癫痫持续状态模型的建立及其自发性反复癫痫发作的研究

    Institute of Scientific and Technical Information of China (English)

    齐兆鹏; 金澎; 刘占涛; 孙鹏; 苏明明

    2011-01-01

    Objective To establish a reliable post-status epilepticus model of temporal lobe epilepsy in rats that mimics human temporal lobe epilepsy, and observe the occurrence of spontaneous recurrent seizures (SRS). Methods Status epilepticus which was monitored for 3 h was induced by a 20-min stimulation of the amygdala ( 100 ms train of 1 ms, 60 Hz bipolar pulses, 400 μA, every 0. 5 s). Stimulated rats ( n =21 ) were monitored with a video recording system for the 3-months follow-up period to record the appearance of SRS. Results SRS (total number 181 ) were detected in 14 of the 21 animals (67%) after a latency period of 8 to 73 days (mean 43 days), including 10 times of stage 3 seizure (5.53%), 77 times of stage 4 seizure (42. 54% ), and 94 times of stage 5 seizure (51.93%). Of all the 14 rats, the seizure number beyond 30 was observed in 3 animals, from 20 to 30 in one animal, from 10 to 20 in 2 animals, between 5 and 10 in 2 animals, and less than 5 in 6 animals. Seventy-three percent of SRS appeared during daytime (07: 00-19: 00) and 74 percent of secondarily generalized seizures occurred during daytime. Conclusion This study has been successfully designed to develop a post-status epilepticus animal model induced by electrical stimulation of the amygdale.%目的 建立癫痫持续状态后颞叶癫痫模型,观察大鼠自发性反复发作(SRS)。方法 持续电刺激大鼠杏仁核20 min(单相方波,强度400μA,波宽1 ms,串长100 ms,串隔0.5s,频率60Hz)引发癫痫持续状态(SE),随后进行3h的SE观察,包括大鼠行为表现和脑电变化。SE状态引出后,进行3个月的视频监测,观察大鼠自发性发作的发作情况并进行分组。结果 经过为期3个月的视频观察,出现SRS14只(67%);未出现者7只(33%)。共记录到3~5级发作181次。其中3级发作10次(5.53%),4级发作77次(42.54%),5级发作94次(51.93%)。发作在30次以上者3只;20 ~ 30次者1只;10 ~20次者2只,5~10次者2只;5

  18. Methylprednisolone pulse therapy of Lennox- Gastaut syndrome with electrical status epilepticus during sleep%甲基泼尼松龙冲击治疗Lennox-Gastaut综合征合并睡眠期癫癎性脑电持续状态

    Institute of Scientific and Technical Information of China (English)

    黄铁栓; 朱金兰; 胡雁; 李冰; 廖建湘

    2005-01-01

    目的 Lennox- Gastaut综合征(LGS)为一种难治性的儿童癫癎综合征,部分患儿合并睡眠期癫癎性电持续状态(electrical status epilepticus during sleep ,ESES)增加了治疗的难度.该文观察了大剂量甲基泼尼松龙冲击治疗LGS合并ESES的近期疗效.方法 22例经视频脑电图或动态脑电图证实合并ESES的LGS患儿,给予甲基泼尼松龙冲击治疗以及口服泼尼松维持治疗.冲击治疗后两周评价临床发作并复查脑电图.结果 22例患者中,15例临床发作减少,16例癫癎样放电减少,未见严重不良反应.结论甲基泼尼松龙冲击治疗可减少LGS患儿发作及脑电图放电,在抗癫癎药物治疗无效时可考虑使用.

  19. Evaluation of treatment effect of sodium valproate for convulsive status epilepticus of cerebral arterial thrombosis%丙戊酸钠对于缺血性脑卒中惊厥性癫痫持续状态的治疗效果评价

    Institute of Scientific and Technical Information of China (English)

    赵勇刚

    2015-01-01

    目的:探讨丙戊酸钠(SV)治疗缺血性脑卒中惊厥性癫痫持续状态(CSE)的效果。方法:收治CSE患者38例,采用 SV 治疗,观察治疗效果。结果:治疗成功24例(63.15%),4例患者发生不良反应。10例(29.4%)难治性 CSE 的mRS>3;实验室检查无明显恶化。结论:SV治疗缺血性脑卒中后CSE安全有效,特别是mRS低分值患者。%Objective:To explore the treatment effect of sodium valproate(SV) for convulsive status epilepticus(CSE) of cerebral arterial thrombosis.Methods:38 patients with CSE were selected.They were treated with SV.We observed the effect of treatment. Results:24 cases(63.15% ) were treated successfully,and 4 cases had adverse reactions.The mRS was greater than 3 of 10 patients(29.4% ) with intractable CSE,and laboratory tests showed no deterioration.Conclusion:SV was safe and effective for treating CSE after cerebral arterial thrombosis,especially for patients with low mRS scores.

  20. Hepatic encephalopathy with status epileptics: A case report

    Institute of Scientific and Technical Information of China (English)

    Hiroto Tanaka; Hiroki Ueda; Yohei Kida; Hiroko Hamagami; Tomikimi Tsuji; Masakazu Ichinose

    2006-01-01

    A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epileptic us. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy (phenytoin sodium) and treatment for hepatic encephalopathy (Branched chain amino acids). The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

  1. FREQUENCY, ETIOLOGY AND IMMEDIATE OUTCOME OF CHILDREN ADMITTED TO PEDIATRIC INTENSIVE CARE UNIT (PICU) WITH CONVULSIVE STATUS EPI LEPTICUS IN KASHMIR NORTH INDIA

    OpenAIRE

    Muzafar; Suhail; Sartaj; Waseem; Aliya; Mudasir

    2015-01-01

    BACKGROUND: Convulsive status epilepticus (CSE) is one of the common causes of childhood hospitalization to PICU with significant morbidity and mortality. Objective of current study was to know the Frequency, etiology and immediate outcome of children admitted to Pediatric Intensive Care Unit (PICU) with convulsive Status Epilepticus in Kashmir Nor...

  2. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  3. Effects of cyclooxygenase-2 selective inhibitor Celecoxib on the expression of P-glycoprotein in rat with status epilepticus%环氧化酶-2选择性抑制剂塞来考昔对癫(癎)持续状态大鼠脑组织P-糖蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    王雪莹; 黄绍平; 宋婷婷; 李丹; 杨琳

    2015-01-01

    目的 研究环氧化酶-2(COX-2)选择性抑制剂塞来考昔对癫(癎)持续状态大鼠脑组织中P-糖蛋白(P-gp)表达的影响,为寻找治疗难治性癫(癎)的新药物提供理论依据.方法 健康成年雄性SD大鼠60只按随机数字表法随机分为空白对照组、癫(癎)模型组和塞来考昔干预组.氯化锂-毛果芸香碱诱发SD大鼠癫(癎)持续状态,48只纳入实验,每组16只.各实验组均采用免疫组织化学法和Western blot法检测鼠额叶皮质区及海马区P-gp的表达情况.结果 免疫组织化学结果显示:与空白对照组比较,癫(癎)模型组中P-gp的表达显著增高,差异有统计学意义(P<0.01);塞来考昔干预后的大鼠脑组织P-gp较癫(癎)模型组显著下降,差异有统计学意义(P<0.01).Western blot法检测结果提示:各组额叶皮层和海马中均有P-gp的表达.与空白对照组比较,癫(癎)模型组中P-gp的表达量显著增高,差异有统计学意义(P<0.01);塞来考昔干预组大鼠脑组织P-gp的表达量较癫(癎)模型组显著下降,差异有统计学意义(P<0.05).结论 COX-2抑制剂塞来考昔可降低P-gp在癫(癎)持续状态大鼠脑组织中的表达,有望成为治疗难治性癫(癎)的新方法.%Objective To study the effect of cyclooxygenase-2 (COX-2)selective inhibitor Celecoxib on the expression of P-glycoprotein(P-gp)in the brain of rats with status epilepficus,in order to assess the therapeutic value of intractable epilepsy.Methods Sixty adult male SD rats were randomly divided into blank control group,the epilepsy model group and Celecoxib intervention group.The status epilepticus was induced in rats by injecting Lithium pilocarpine.Forty-eight rats were included in the experiment.There were 16 rats in each of the blank control group,epilepsy model group and Celecoxib intervention group,respectively.Immunohistochemical method and Western blot method were used to detect the expression of P-gp in experimental group in the

  4. Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures.

    Science.gov (United States)

    Lintunen, Minnamaija; Sallmen, Tina; Karlstedt, Kaj; Panula, Pertti

    2005-10-01

    Increased brain histamine is reported to protect against convulsions. We used systemic kainic acid (KA) administration to study possible changes of the histaminergic system in rat brain in status epilepticus (SE). Robust increases in brain histamine concentrations and numbers of histamine-immunoreactive nerve fibers were detected in the piriform cortex (Pir) and amygdala after KA injection, suggesting a reactive increase, which is opposite to other published aminergic transmitter responses. These changes, lasting several weeks, might be coupled to a mechanism unrelated to the anticonvulsive function of histamine. Transient increases in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop, coupled to mitogen-activated protein kinase pathway, were detected first in the hippocampal CA3c area, followed by the Pir and amygdala and then the hippocampal CA1 area. These results suggest that histamine and H3 receptors, which also control the release of GABA and glutamate, might be involved in convulsive SE.

  5. [Refractory status epilepticus presenting as shaken baby syndrome].

    Science.gov (United States)

    Fernandez-Menendez, Andrea; Buenache-Espartosa, Raquel; Coca-Perez, Ana; Morillo-Carnero, Pablo; Martinez-San Millan, Juan; Lorenzo-Sanz, Gustavo

    2014-06-16

    Introduccion. El estado convulsivo en el lactante suele ser desencadenado por un sindrome febril secundario a una infeccion intercurrente o una infeccion del sistema nervioso central. El sindrome del bebe zarandeado se caracteriza por la asociacion de hemorragia subdural bilateral o multifocal, hemorragia retiniana y encefalopatia. Los niños menores de 1 año constituyen el grupo de mayor riesgo, con un pico de incidencia maxima entre las 10 y 16 semanas de vida. Los procesos intercurrentes, como los colicos del lactante o los sindromes febriles que favorecen el llanto, suelen ser factores precipitantes del zarandeo. Casos clinicos. Presentamos los casos de dos lactantes que en el contexto de un sindrome febril comenzaron con un estado epileptico. En las pruebas de imagen se evidenciaron hematomas subdurales bilaterales en diferente estadio evolutivo y en el fondo de ojo se observaron hemorragias retinianas bilaterales en ambos niños. Conclusiones. En un niño con un proceso febril inespecifico que desarrolla un estado convulsivo se debe pensar, ademas de en los problemas mas habituales, en el sindrome del bebe zarandeado como posible causa etiologica, sobre todo si es menor de 6 meses.

  6. Protective effect and mechanism of rHuEPO against status epilepticus-induced neuron apoptosis in rats%重组人红细胞生成素对大鼠癫痫持续状态诱导的神经元凋亡的保护机制

    Institute of Scientific and Technical Information of China (English)

    潘振华; 徐院花; 田田

    2015-01-01

    目的:探讨重组人红细胞生成素(rHuEPO)对大鼠癫痫持续状态(SE)诱导的神经元凋亡的保护机制。方法 SD大鼠60只随机均分为五组:A组为空白对照;其余四组采用海人酸(KA)点燃大鼠SE模型后,B组作为模型对照,C组用rHuEPO处理,D组用rHuEPO和LY294002处理,E组用二甲基亚砜(LY294002的溶剂)处理。Western blot法检测Akt、p‐Akt、Bcl‐2和Bax蛋白表达;定量RT‐PCR检测Bcl‐2和Bax mRNA表达。结果 C组Bcl‐2 mRNA表达量高于B组(P<0.05),D组p‐Akt蛋白表达低于C组(P<0.05)。结论 rHuEPO对SD大鼠SE诱导的海马神经元具有保护作用;其机制可能是通过PI3K/Akt途径对线粒体凋亡途径相关调控因子Bcl‐2和Bax进行调控,进而介导线粒体凋亡途径,抑制细胞凋亡。%Objective To explore the protective effect and underlying mechanism of recombinant human erythropoietin(rHuEPO) against status epilepticus(SE)‐induced neuron apoptosis in rats .Methods Sixty SD rats were equally divided into 5 groups .Group A was taken as blank control .SE models were established by kainic acid(KA) in the other 4 groups .Group B was taken as model control .Group C was treated with rHuEPO ,group D was treated with rHuEPO and LY294002 , and group E was treated with DMSO(a solvent of LY294002) .The protein expressions of Akt ,p‐Akt , Bcl‐2 and Bax were detected by Western blot .The mRNA expressions of Bcl‐2 and Bax were detected by qRT‐PCR .Results Bcl‐2 mRNA expression was higher in group C than that in group B (P<0 .05) .The expression of p‐Akt protein was less in group D than that in group C (P<0 .05) . Conclusion The rHuEPO has a neuroprotective effect on SE‐induced neuron apoptosis in rats .The mechanism for that may be through PI3K/AKT pathway to regulate the expressions of Bcl‐2 and Bax , which mediates mitochondrial apoptotic pathways and inhibits cell apoptosis .

  7. Status of memory loss.

    LENUS (Irish Health Repository)

    Iyer, Parameswaran Mahadeva

    2012-01-01

    A 72-year-old woman presented with first onset of seizure with no prior history of cognitive dysfunction. EEG revealed focal non-convulsive status epilepticus. MRI brain showed a left temporal non-enhancing lesion. Temporal pole biopsy showed acute neuronal necrosis and astrocyte hyperplasia together with extensive amyloid plaques and neurofibrillary tangles. Perivascular oligodendroglial hyperplasia was present. Postmortem examination revealed extensive plaque and tangle disease. Perivascular oligodendroglial hyperplasia was limited to the left temporal area. The presence of focal perivascular oligodendroglial hyperplasia in the left temporal cortex, combined with extensive plaque and tangle disease may have contributed to the focal status epilepticus in this patient. Although the presence of focal perivascular oligodendroglial hyperplasia has been reported in cases of temporal lobe epilepsy, it has not been reported as a cause of seizure in patients with Alzheimer\\'s disease previously. Further studies for clinical-pathologic correlation would be required to confirm this hypothesis.

  8. GluN2A 抑制剂对癫痫持续状态大鼠脑内P-糖蛋白表达的影响%Effect of GluN2A Inhibitor on Expression of P-glycoprotein in Rats with Status Epilepticus

    Institute of Scientific and Technical Information of China (English)

    邓镇; 罗淼珊; 赵元淑; 余涵; 谢柳; 陈丽; 朱晓琴; 胡景鑫; 雷水生

    2014-01-01

    rats were first intracerebroventricularly injected with saline and then intraperitoneally injected with pentylenetetrazole ;inhibitor interven-tion group ,in which the rats were intracerebroventricularly administrated with PEAQX ,and then intraperitoneally with pentyle-netetrazole.The behavior manifestations of rats were observed ,and the electroencephalogram (EEG) changes of rats were recor-ded with BL-420E biological and functional experimental system.The expression changes of P-gp in the hippocampus in each group were examined by real-time quantitative PCR (RT-qPCR) and Western blot.Results Behavioral observation showed that rats in the control group had no obvious epileptic seizures ,and those in epileptic group presented with significant and fast sei-zures ,which suggested that status epilepticus models were successfully established.In the inhibitor intervention group ,a long incubation period of seizures was found and the seizures were less obvious.EEG showed no significant epileptiform waves in the control group but vertex sharp transient wave ,sharp wave and composite wave and so on in the epileptic group.In the inhibitor intervention group ,the waves diminished or disappeared.The results of RT-qPCR showed that the expression of P-gp mRNA in the hippocampus of epileptic group was increased obviously ,while it was significantly reduced in the inhibitor intervention group.The results of Western blot were consistent with those of RT-qPCR.Conclusion The GluN2A inhibitor PEAQX could reduce the epileptic seizures and the expression of P-gp by inhibiting the activity of GluN2A.The findings suggested that the se-lective inhibitors of GluN2A might attenuate the drug resistance in epilepsy.

  9. Clinical Characteristics and Prognosis of Idiopathic Occipital Epilepsy and Electrical Status Epilepticus in Sleeping Children%特发性儿童枕叶癫(癎)伴睡眠期癫(癎)性电持续状态的临床特征及预后

    Institute of Scientific and Technical Information of China (English)

    张胜; 罗序峰; 付四毛; 朱建平; 吴涛

    2012-01-01

    Objective To investigate the clinical manifestations, electroencephalogram(EEG) characteristics, treatment response and prognosis of children with idiopathic occipital epilepsy and electrical status epilepticus in sleep (ESES) . Methods Clinical and EEG data of 8 cases with idiopathic occipital epilepsy and ESES were analyzed together with follow - up for treatment and prognosis. Results The onset age varied from 5 years and 8 months to 8 years and 4 months in the 8 cases. All the 8 cases had neuropsychological injury and motor regression, but had no history of family epilepsy and clear abnormalities by brain imaging examination. Seven patients had seizures, performing exercise - induced limited seizures after waking up; seizures could also attack during awaking period ,including exercise - induced limited seizures (5/7 cases) and overall tonic -clonic seizures (2/7 cases). Antiepileptic drugs (AEDs) reduced attacks in 4 cases,but did not improve the psychological damage to nerve and motor rcgression obviously. Mild improvement in neuropsychological injury and EEG were observed in 3 cases treated with single drug Oxcarbazepine ( OXC). Six cases, who were treated with intravenous methylprednisolone shock therapy, had ideal control, and 1 case had marked improvement of nerve injury and psychological setback in movement. Eight patients were followed up by EEG for 0. 5 -2. 0 years,and 2 cases improved in ESES phenomenon. Up to follow - up,the 8 cases of patients still had mental retardation compared with healthy children in the same age. Conclusions Idiopathic occipital epilepsy is an age - dependent benign epilepsy in children; AEDs are often ineffective when the EEG showes ESES of the patients; hormones can reduce the clinical attack, but can not improve the psychological nerve damage and phenomenon of EEG ESES. Children with poor response to corticosteroids can be treated with OXC monothe-rapy or combined therapy.%目的 探讨特发性枕叶癫(癎)伴睡眠期

  10. Absence status associated with focal activity and polydipsia-induced hyponatremia

    OpenAIRE

    Azuma, Hideki

    2008-01-01

    Hideki Azuma, Tatsuo Akechi, Toshi A FurukawaDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanAbstract: We report a case of de novo absence status associated with focal discharge and polydipsia-induced hyponatremia. Nonconvulsive status epilepticus (NCSE) is classified as absence status or complex partial status. Absence status is characterized by bilateral synchronized spike and wave complex bursts and a vari...

  11. Amoxicillin/clavulanic acid-induced pemphigus vulgaris: case report.

    Science.gov (United States)

    Baroni, Adone; Russo, Teresa; Faccenda, Franco; Piccolo, Vincenzo

    2012-01-01

    Drug-induced pemphigus is a well-established variety of pemphigus, presenting with clinical and histopathologic features identical to idiopathic form. Medical history plays a fundamental role in the diagnosis of drug-induced pemphigus. A large variety of drugs have been implicated in its pathogenesis and they may induce acantholysis via biochemical and/or immune mechanism. We present a case of a 69-year-old woman affected by amoxicillin/clavulanic acid-induced pemphigus and discuss its pathogenetic mechanism.

  12. 重组人红细胞生成素对癫痫持续状态大鼠海马线粒体凋亡途径相关调控因子的影响及作用机制%Effects of rHuEPO on the Regulatory Factors Related With the Apoptosis Pathway of Hippocampal Mitochondria in Rats With Status Epilepticus and the Possible Mechanism

    Institute of Scientific and Technical Information of China (English)

    史志勤; 卞红磊; 魏艳静; 尹晓琳; 张荣; 梁文杰; 刘瑞春; 王维平; 于江华

    2015-01-01

    制可能是rHuEPO活化PI3K/Akt后,提高p-Akt蛋白及线粒体凋亡途径相关调控因子XIAP的表达,下调了Bax的表达,从而介导线粒体凋亡途经,发挥抗凋亡、促存活的神经保护作用。%Objective To observe the effect of recombinant human erythropoietin( rHuEPO)on the expression levels of p-PKB/p-Akt,Bax and XIAP in hippocampal neurons of male mature SD rats with pentylenetetrazol( PTZ)induced status epilepticus( SE),and to further investigate the possible mechanism. Methods The included male mature rats of clean grade were provided by Laboratory Animal Center of Hebei Province in March 2010. By using the PTZ kindling epileptic rat SE model, the SD rats were divided into four groups:group B( PTZ+0. 9% sodium chloride solution),group C( PTZ+rHuEPO),group D(PTZ+LY294002+rHuEPO)and group E(PTZ+dimethyl sulfoxide+rHuEPO). Meanwhile,we assigned SD rats without SE model building into group A(0. 9% sodium chloride solution). The behavioral and EEG changes were detected;TUNEL was used to check the apoptosis status of hippocampal neurons;immunohistochemistry was used to observe the number of cells with positive p-Akt, Bax and XIAP;the RT - PCR method was used to detect the expression level of BaxmRNA in hippocampus;Western blot method was employed to detect the protein expression levels of Akt,p-Akt and XIAP. Results Compared with group B,group C was higher(P<0. 05)in the number of cells with positive p-Akt and XIAP,the protein expression levels of p-Akt and XIAP and was lower in the number of cells with positive Bax and the protein expression level of BaxmRNA. Compared with group C,group D was lower in the number of cells with positive p-Akt and XIAP and the protein expression levels of p-Akta and XIAP and was higher(P <0. 05)in the number of positive cells with positive Bax and the expression level of BaxmRNA. Conclusion rHuEPO can increase the number of cells with positive p-Akt and XIAP and the protein expression of p-Akt and XIAP. It can also decrease the

  13. Adult status epilepticus emergency care of adult status epilepticus%成人癫痫持续状态的急救护理

    Institute of Scientific and Technical Information of China (English)

    梁燕冰; 关常青; 梁庆元

    2010-01-01

    目的:探讨成人癫痫持续状态的急救护理.方法:对28例癫痫持续状态的急救与护理资料进行回顾性分析.结果:治愈27例(96.43%),死亡1例(3.57%).结论:癫痫发作时正确的急救护理可改善患者预后.

  14. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  15. Nerve cell apoptosis channel after statural epilepticus%癫痫持续状态后神经细胞凋亡途径

    Institute of Scientific and Technical Information of China (English)

    喻良; 梁益; 孙红斌

    2008-01-01

    凋亡是癫痫持续状态(status epilepticus,SE)后神经元损伤的重要形式.SE后的神经细胞凋亡主要通过内源性和外源性两条凋亡途径,最终通过easpase-3的激活导致核内染色体DNA的阶段性降解.此外还有不依赖于caspase的凋亡途径.本文对SE后神经细胞凋亡的不同途径进行综述,以了解SE后神经细胞凋亡的机制.

  16. Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-03-01

    The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities.

  17. 癫(痫)持续状态的治疗进展%Advances in treatment of status epilepticas

    Institute of Scientific and Technical Information of China (English)

    高旭光

    2009-01-01

    @@ 1概述 癫(痫)持续状态(status epilepticus,SE)又称癫(痫)状态,即癫(痫)发作频繁出现,以至于患者在一次发作后意识尚不能完全恢复的情况下,又进入了下一次发作.

  18. [Electrical status epilepticus during sleep: a retrospective multi-centre study of 29 cases].

    Science.gov (United States)

    Lorenzo-Ruiz, María; Miguel-Martin, Beatriz; García-Pérez, Asunción; Martínez-Granero, Miguel A; Aguilera-Albesa, Sergio; Yoldi-Petri, M Eugenia; Sánchez-Ruiz de Gordoa, Javier; Castro-De Castro, Pedro; Sánchez-Carpintero, Rocío

    2015-02-01

    Introduccion. El estado epileptico electrico durante el sueño (ESES) es un sindrome epileptico caracterizado por la presencia de descargas epilepticas tipo punta-onda lenta de manera muy persistente durante el sueño no REM. En la actualidad, el manejo de esta patologia es heterogeneo y no hay estudios controlados con los tratamientos utilizados, ni se ha comprobado si estos mejoran la evolucion cognitiva de los pacientes. Pacientes y metodos. Se revisan los pacientes diagnosticados de ESES durante 15 años en cuatro centros hospitalarios, se recoge la presentacion clinica, el manejo terapeutico y la evolucion clinica, y se compara con la bibliografia. Resultados. Se seleccionaron 29 pacientes con ESES, 20 de ellos idiopatico y 26 de ellos generalizado. Los farmacos con los que se consiguio mayor control de la actividad electrica fueron los corticoides/hormona adrenocorticotropa (ACTH), el clobazam y el levetiracetam. La mediana de duracion del ESES en los casos primarios fue de seis meses, y en los secundarios, el doble. El 45% de los pacientes mantuvo un cociente intelectual normal y un 40% presento en la evolucion discapacidad cognitiva de diferente grado. Conclusiones. El pronostico neuropsicologico evolutivo suele ser desfavorable y la evolucion cognitiva parece estar en relacion con la duracion del ESES y el area donde este concentrada la actividad epileptica, lo que sugiere que el mal pronostico, si se trata precozmente, se puede evitar. Los antiepilepticos mas frecuentemente utilizados son el acido valproico, la etosuximida y el levetiracetam, y en nuestra muestra tambien se utilizaron con frecuencia el clobazam y la lamotrigina. Los farmacos mas eficaces para el control del ESES fueron los corticoides/ACTH, el clobazam y el levetiracetam.

  19. Which insights have we gained from the kindling and post-status epilepticus models?

    NARCIS (Netherlands)

    J.A. Gorter; E.A. van Vliet; F.H. Lopes da Silva

    2015-01-01

    Experimental animal epilepsy research got a big boost since the discovery that daily mild and short (seconds) tetanic stimulations in selected brain regions led to seizures with increasing duration and severity. This model that was developed by Goddard (1967) became known as the kindling model for e

  20. Magnesium treatment for patients with refractory status epilepticus due to POLG1-mutations

    NARCIS (Netherlands)

    Visser, Nora A; Braun, Kees P J; Leijten, Frans S S; van Nieuwenhuizen, Onno; Wokke, John H J; van den Bergh, Walter M

    2011-01-01

    Mutations in the gene encoding of the catalytic subunit of mtDNA polymerase gamma (POLG1) can cause typical Alpers' syndrome. Recently, a new POLG1 mutation phenotype was described, the so-called juvenile-onset Alpers' syndrome. This POLG1 mutation phenotype is characterized by refractory epilepsy w

  1. Transient MRI abnormalities associated with partial status epilepticus: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Amato, Carmelo E-mail: c6amato@hotmail.com; Elia, Maurizio; Musumeci, Sebastiano A.; Bisceglie, Pierluigi; Moschini, Massimo

    2001-04-01

    We report the case of an 18-year-old woman who presented a long-lasting cluster of partial seizures, and MRI cortical abnormalities localized in the left parietal lobe. The MRI changes correlated with the site of the epileptogenic focus, and disappeared within 2 weeks. The recognition of these reversible MRI abnormalities, which are presumably due to a temporary alteration of blood-brain barrier in the epileptogenic zone with subsequent edema, and are not associated with any underlying organic conditions, is extremely useful in the medical management of the patient and allows to avoid other invasive diagnostic procedures.

  2. [Descriptive statistical analysis of the treatment of status epilepticus in a referral hospital].

    Science.gov (United States)

    Hortigüela-Saeta, M Montesclaros; Conejo-Moreno, David; Gutiérrez-Moreno, Miriam; Gómez-Saiz, Luna

    2015-05-16

    Introduccion. Los estados epilepticos se definen como crisis recurrentes sin recuperacion de la conciencia entre ellas o una sola crisis de mas de 30 minutos. Objetivos. Realizar un analisis descriptivo de los datos mas relevantes de pacientes con estados epilepticos ingresados en la unidad de cuidados intensivos pediatricos (UCIP) y revisar los factores de riesgo asociados a estado epileptico de mal pronostico. Pacientes y metodos. Se estudiaron las variables principales de los pacientes ingresados en la UCIP con estado epileptico de un hospital terciario en un periodo de seis años. Resultados. Se recogieron 68 pacientes (el 55,9%, varones) con una edad media de 3,7 años. La semiologia mas frecuente fue en forma de crisis tonicoclonicas generalizadas (50%). La duracion media de los estados epilepticos fue de 51,44 minutos. Se utilizaron 3,21 farmacos antiepilepticos de media para yugular las crisis, y la media de farmacos utilizados previamente al ingreso en la UCIP fue de 2,37. El farmaco de primera linea mas utilizado fue el diacepam (83,8%) rectal (75%), seguido del diacepam (52,9%) por via intravenosa en segundo lugar, y la fenitoina fue el farmaco mas utilizado como tercera linea. La causa mas frecuente de estado epileptico fue padecer epilepsia previa (33,9%), y el sindrome de Dravet fue la etiologia epileptica mas frecuente. Conclusiones. El tratamiento de los estados epilepticos es complejo y exige un manejo multidisciplinar e individualizado. Es necesaria la elaboracion y revision de protocolos y guias clinicas para un adecuado manejo de estos pacientes.

  3. [Status epilepticus in paediatrics: a retrospective study and review of the literature].

    Science.gov (United States)

    Moreno-Medinilla, Esther E; Negrillo-Ruano, Rocío; Calvo-Medina, Rocío; Mora-Ramírez, M Dolores; Martínez-Antón, Jacinto L

    2015-05-01

    Introduccion. El estado epileptico (EE) es la emergencia neurologica mas frecuente en pediatria. Dada la posibilidad de secuelas neurologicas y mortalidad asociadas, requiere un tratamiento agresivo precoz. Pacientes y metodos. Estudio descriptivo retrospectivo a traves de la revision de historias clinicas de pacientes ingresados en nuestro hospital entre 2010-2013 con diagnostico de EE. El objetivo fue describir las caracteristicas epidemiologicas y el manejo de estos pacientes, asi como revisar la bibliografia disponible sobre este tema. Resultados. Hemos recogido 39 pacientes (25 varones) y 51 episodios de EE. Edad media: 4,8 años. Tenian enfermedad de base 22 pacientes. Dieciocho eran epilepticos conocidos y cinco tuvieron un EE previo. De los 51 episodios de EE, 33 fueron sintomaticos, 15 febriles y tres criptogenicos. Los tipos de EE fueron: 25 parciales (de ellos, 16 complejos) y 26 generalizados. El tratamiento de primera eleccion fue benzodiacepinas en 47 pacientes (40, diacepam), fenitoina en tres y acido valproico en uno. Veintisiete pacientes precisaron farmacos de segunda linea: 16, acido valproico; ocho, fenitoina; dos, fenobarbital; y uno, levetiracetam. Diez pacientes precisaron farmacos de tercera linea para la induccion del coma: el midazolam fue el mas utilizado en nuestro centro, seguido del tiopental y el propofol. Dos EE superrefractarios requirieron inmunoglobulinas y corticoides sistemicos por presentarse en el curso de encefalitis autoinmunes. Conclusiones. Debe plantearse el esquema terapeutico del EE desde el inicio de cualquier crisis convulsiva. El tratamiento es escalonado, con benzodiacepinas en la primera etapa, antiepilepticos de amplio espectro y disponibilidad intravenosa en la segunda (acido valproico, levetiracetam en el EE generalizado y fenitoina en el EE focal), mientras que el tercer nivel varia en funcion de la experiencia de cada equipo.

  4. Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus.

    Science.gov (United States)

    Kämppi, Leena; Ritvanen, Jaakko; Mustonen, Harri; Soinila, Seppo

    2015-01-01

    Introduction. This study was designed to identify the delays and factors related to and predicting the cessation of generalized convulsive SE (GCSE). Methods. This retrospective study includes 70 consecutive patients (>16 years) diagnosed with GCSE and treated in the emergency department of a tertiary hospital over 2 years. We defined cessation of SE stepwise using clinical seizure freedom, achievement of burst-suppression, and return of consciousness as endpoints and calculated delays for these cessation markers. In addition 10 treatment delay parameters and 7 prognostic and GCSE episode related factors were defined. Multiple statistical analyses were performed on their relation to cessation markers. Results. Onset-to-second-stage-medication (p = 0.027), onset-to-burst-suppression (p = 0.005), and onset-to-clinical-seizure-freedom (p = 0.035) delays correlated with the onset-to-consciousness delay. We detected no correlation between age, epilepsy, STESS, prestatus period, type of SE onset, effect of the first medication, and cessation of SE. Conclusion. Our study demonstrates that rapid administration of second-stage medication and early obtainment of clinical seizure freedom and burst-suppression predict early return of consciousness, an unambiguous marker for the end of SE. We propose that delays in treatment chain may be more significant determinants of SE cessation than the previously established outcome predictors. Thus, streamlining the treatment chain is advocated. PMID:26347816

  5. Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Leena Kämppi

    2015-01-01

    Full Text Available Introduction. This study was designed to identify the delays and factors related to and predicting the cessation of generalized convulsive SE (GCSE. Methods. This retrospective study includes 70 consecutive patients (>16 years diagnosed with GCSE and treated in the emergency department of a tertiary hospital over 2 years. We defined cessation of SE stepwise using clinical seizure freedom, achievement of burst-suppression, and return of consciousness as endpoints and calculated delays for these cessation markers. In addition 10 treatment delay parameters and 7 prognostic and GCSE episode related factors were defined. Multiple statistical analyses were performed on their relation to cessation markers. Results. Onset-to-second-stage-medication (p=0.027, onset-to-burst-suppression (p=0.005, and onset-to-clinical-seizure-freedom (p=0.035 delays correlated with the onset-to-consciousness delay. We detected no correlation between age, epilepsy, STESS, prestatus period, type of SE onset, effect of the first medication, and cessation of SE. Conclusion. Our study demonstrates that rapid administration of second-stage medication and early obtainment of clinical seizure freedom and burst-suppression predict early return of consciousness, an unambiguous marker for the end of SE. We propose that delays in treatment chain may be more significant determinants of SE cessation than the previously established outcome predictors. Thus, streamlining the treatment chain is advocated.

  6. Rare presentation of a common disease: Idiopathic hypoparathyroidism presenting with extrapyramidal symptoms and status epilepticus

    Directory of Open Access Journals (Sweden)

    Kaushik Ghosh

    2012-01-01

    Full Text Available We report of an 18-year-old male who presented with an epileptiform disorder, features of hypocalcemia, and an extrapyramidal symptom in the form of choreoathetosis. On evaluation he had idiopathic hypoparathyroidism with extensive calcifications in the extrapyramidal system of the brain; basal ganglion, as well as in the cerebral cortex and cerebellum, which is a rare entity. We report the rare presentation of a common disorder, which requires to be considered in evaluating hypoparathyroidism.

  7. The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats

    NARCIS (Netherlands)

    Suleymanova, E.M.; Shangaraeva, V.A.; Rijn, C.M. van; Vinogradova, L.V.

    2016-01-01

    An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acu

  8. Adrenal failure followed by status epilepticus and hemolytic anemia in primary antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Bures Vladimir

    2005-04-01

    Full Text Available Abstract We report on a 14 year old boy who presented with the symptoms abdominal pain, fever and proteinuria. A hematoma in the region of the right pararenal space was diagnosed. Prothrombin time and activated partial thromboplastin time were prolonged, lupus anticoagulant and anticardiolipin antibodies were positive and serum cortisol was normal. Ten days after admission the boy suddenly suffered generalized seizures due to low serum sodium. As well, the patient developed hemolytic anemia, acute elevated liver enzymes, hematuria and increased proteinuria. At this time a second hemorrhage of the left adrenal gland was documented. Adrenal function tests revealed adrenal insufficiency. We suspected microthromboses in the adrenals and secondary bleeding and treated the boy with hydrocortisone, fludrocortisone and phenprocoumon. Conclusion Adrenal failure is a rare complication of APS in children with only five cases reported to date. As shown in our patient, this syndrome can manifest in a diverse set of simultaneously occurring symptoms.

  9. Nonconvulsive status epilepticus and Creutzfeldt–Jakob-like EEG changes in a case of lithium toxicity

    Directory of Open Access Journals (Sweden)

    B.K. Madhusudhan

    2014-01-01

    This case highlights the importance of therapeutic drug-level monitoring of lithium, especially where toxicity is suspected, and the important role electroencephalography plays in diagnosing NCSE and its management.

  10. Salivary a-amylase protects enamel surface against acid induced softening

    DEFF Research Database (Denmark)

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend;

    -TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had...... an explanatory power of 39% in the analysis with high concentrations being most protective (pamylase on protective effect to 65...

  11. Volatile anesthetic for the control of posthypoxic refractory myoclonic status

    Directory of Open Access Journals (Sweden)

    Vivek Rayadurg

    2016-01-01

    Full Text Available Posthypoxic myoclonus (Lance-Adams syndrome is characterized by myoclonus involving multiple muscle groups which is resistant to most conventional antiepileptic drugs. We present a case of hypoxic brain injury-induced myoclonic status epilepticus successfully controlled with isoflurane. The antimyoclonic effects of isoflurane are likely due to potentiation of inhibitory postsynaptic GABA A receptor-mediated currents and its effects on thalamocortical pathways. It is effective even when intravenous agents fail to control myoclonus. It may be a useful alternative to intravenous anesthetics as a third tier therapy in patients with refractory status myoclonus.

  12. The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells.

    Science.gov (United States)

    Cho, Hye In; Kim, Min Seong; Jang, Yeun Kyu

    2016-08-01

    The scaffold protein BRPF2 (also called BRD1), a key component of histone acetyltransferase complexes, plays an important role in embryonic development, but its function in the differentiation of embryonic stem cells (ESCs) remains unknown. In the present study, we investigated whether BRPF2 is involved in mouse ESC differentiation. BRPF2 depletion resulted in abnormal formation of embryoid bodies, downregulation of differentiation-associated genes, and persistent maintenance of alkaline phosphatase activity even after retinoic acid-induced differentiation, indicating impaired differentiation of BRPF2-depleted ESCs. We also found reduced global acetylation of histone H3 lysine 14 (H3K14) in BRPF2-depleted ESCs, irrespective of differentiation status. Further, co-immunoprecipitation analysis revealed a physical association between BRPF2 and the histone acetyltransferase MOZ in differentiated ESCs, suggesting the role of BRPF2-MOZ complexes in ESC differentiation. Together, these results suggest that BRPF2-MOZ complexes play an important role in the differentiation of ESCs via H3K14 acetylation. PMID:27256846

  13. The role of MAPK signalling pathways in acetic acid-induced cell death of Saccharomyces cerevisiae

    OpenAIRE

    Azevedo, Flávio Humberto Torres Dias Feio de

    2011-01-01

    Dissertação de mestrado em Genética Molecular Mitogenic Activated Protein Kinase (MAPK) cascades are important signalling pathways that allow yeast cells to swiftly adapt to changing environmental conditions. Previous studies suggested that the High Osmolarity Glycerol (HOG) MAPK pathway and ceramide production are involved in acetic-acid induced apoptosis in yeast. Evidence that changes in the levels of endogenous ceramides can affect yeast cell fate has also been put forth...

  14. Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.

    OpenAIRE

    Handa, S I; FREESTONE, S.

    1990-01-01

    We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

  15. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Science.gov (United States)

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.

  16. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Science.gov (United States)

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

  17. 戊四氮诱导发育鼠癫痫持续状态后海马区HIF-1α的表达及其与神经干细胞增殖的关系%Expression of hypoxia-inducible factor-1 alpha and correlation between HIF-1α level and proliferation of neural stem cells in the hippocampus of developing rats after pentylenetetrazolinduced status epilepticus

    Institute of Scientific and Technical Information of China (English)

    周保健; 袁宝强

    2012-01-01

    Objective To explore the expressions of hypoxia-inducible factor-1 alpha (HIF- lα)and nestin in the hippocampus of developing rats after pentylenetetrazol (PTZ)-induced starus epilepticus (SE),and the correlation between HIF-1α level and proliferation of neural stem cells (NSCs). Methods A total of 768 SD rats,including rats of postnatal 7 days (P7,n-192),rats of postnatal 14 days (P14,n=192),rats of postnatal 21 days (P21,n=192) and rats of postnatal 28 days (P28,n=192),were equally randomized into vehicle group (n=96) and control group (n-96),respectively; SE rat models of the vehicle group were induced by intraperitoneal injection of 1% PTZ (80 mg/kg); and rats of the control group were received injection of normal saline (NS); 6 and 12 h,and 1,2,3 and 7 d after the inducement,the mRNA and protein expressions of HIF-1α in the hippocampus of rats in these 8 groups were examined by RT-PCR and immunohistochemistry, respectively. Another 48 21-d- old SD rats were equally randomized into vehicle I group (n=24) and intervention group (n=24); and rats in the intervention group received injection of HIF-lα antisense oligodeoxynucleotides (ASODN) into the right hippocampus and NS into the left hippocampus; 6 h after the injection,these 48 rats were induced into SE models by intraperitoneal injection of 1% PTZ (80 mg/kg); 2 d after the inducement, the mRNA expression of HIF-1α in the hippocampus was examined by RT-PCR; and 7 and 14 d after theinducement, the protein expressions of HIF-1α and nestin in the hippocampus were examined by immunohistochemistry. Results The mRNA expression of HIF-1 α in the hippocampus of all the rats in the vehicle group after SE increased significantly with similar trend.Six h after SE,the HIF-1α mRNA expression significantly decreased with time prolongation (P<0.05). Major HIF-1α positive cells were located in different areas at different time after SE. In intervention experiment, the HIF-1α mRNA expression 2 d after SE and

  18. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  19. Clavulanic acid induces penile erection and yawning in male rats: comparison with apomorphine.

    Science.gov (United States)

    Sanna, Fabrizio; Melis, Maria Rosaria; Angioni, Laura; Argiolas, Antonio

    2013-02-01

    The beta-lactamase inhibitor clavulanic acid induced penile erection and yawning in a dose dependent manner when given intraperitoneally (IP, 0.05-5mg/kg), perorally (OS, 0.1-5mg/kg) and intracereboventricularly (ICV, 0.01-5 μg/rat) to male rats. The effect resembles that of the dopamine receptor agonist apomorphine given subcutaneously (SC) (0.02-0.25mg/kg), although the responses of the latter followed a U inverted dose-response curve, disappearing at doses higher than 0.1mg/kg. Clavulanic acid responses were reduced by about 55% by haloperidol, a dopamine D2 receptor antagonist (0.1mg/kg IP), and by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist (2 μg/rat ICV), both given 15 min before clavulanic acid. A higher reduction of clavulanic acid responses (more than 80%) was also found with morphine, an opioid receptor agonist (5mg/kg IP), and with mianserin, a serotonin 5HT(2c) receptor antagonist (0.2mg/kg SC). In contrast, no reduction was found with naloxone, an opioid receptor antagonist (1mg/kg IP). The ability of haloperidol, d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin and morphine to reduce clavulanic acid induced penile erection and yawning suggests that clavulanic acid induces these responses, at least in part, by increasing central dopaminergic neurotransmission. Dopamine in turn activates oxytocinergic neurotransmission and centrally released oxytocin induces penile erection and yawning. However, since both penile erection and yawning episodes were reduced not only by the blockade of central dopamine and oxytocin receptors and by the stimulation of opioid receptors, which inhibits oxytocinergic neurotransmission, but also by mianserin, an increase of central serotonin neurotransmission is also likely to participate in these clavulanic acid responses.

  20. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    OpenAIRE

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to a...

  1. Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

    OpenAIRE

    Hayashi, Izumi; Majima, Masataka

    1999-01-01

    Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment...

  2. STRUCTURAL REMODELING OF PROTEOGLYCANS UPON RETINOIC ACID-INDUCED DIFFERENTIATION OF NCCIT CELLS*

    Science.gov (United States)

    Gasimli, Leyla; Stansfield, Hope E.; Nairn, Alison V.; Liu, Haiying; Paluh, Janet L.; Yang, Bo; Dordick, Jonathan S.; Moremen, Kelley W.; Linhardt, Robert J.

    2012-01-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1500-fold and 2800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  3. Structural remodeling of proteoglycans upon retinoic acid-induced differentiation of NCCIT cells.

    Science.gov (United States)

    Gasimli, Leyla; Stansfield, Hope E; Nairn, Alison V; Liu, Haiying; Paluh, Janet L; Yang, Bo; Dordick, Jonathan S; Moremen, Kelley W; Linhardt, Robert J

    2013-07-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1,500-fold and 2,800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  4. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  5. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    Science.gov (United States)

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID:27368415

  6. Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2

    Institute of Scientific and Technical Information of China (English)

    Hua Jiang; Chang-Sheng Deng; Ming Zhang; Jian Xia

    2006-01-01

    AIM: To explore the possible mechanisms of curcumin in rat colitis induced by trinitrobenzene sulfonic (TNBS) acid. METHODS: Rats with TNBS acid-induced colitis were treated with curcumin (30 mg/kg or 60 mg/kg per day ip). Changes of body weight and histological scores as well as survival rate were evaluated. Leukocyte infiltration was detected by myeloperoxidase (MPO)activity assay. The expression of cyclooxygenase-2(COX-2) was detected by RT-PCR and Western blot.Inflammation cytokines were determined by RT-PCR.Local concentration of prostaglandin E2 (PGE2) in colon mucosa was determined by ELISA.RESULTS: Curcumin improved survival rate and histological image, decreased the macroscopic scores and MPO activity. Also curcumin reduced the expression of COX-2 and inflammation cytokines. In addition,treatment with curcumin increased the PGE2 level.CONCLUSION: Curcumin has therapeutic effects on TNBS acid-induced colitis, the mechanisms seem to be related to COX-2 inhibition and PGE2 improvement.

  7. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  8. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Directory of Open Access Journals (Sweden)

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  9. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  10. Acid-induced hyperalgesia and anxio-depressive comorbidity in rats.

    Science.gov (United States)

    Liu, Yu-Ting; Shao, Yen-Wen; Yen, Chen-Tung; Shaw, Fu-Zen

    2014-05-28

    Fibromyalgia is a prevalent disorder characterized by chronic widespread pain (CWP) and complex comorbid symptoms. A CWP model is developed through repeated unilateral intramuscular injections of acid saline resulting in bilateral mechanical hyperalgesia in rats. The present study aims to evaluate whether both anxious and depressive comorbidities exist in this acid-induced pain model, similarly to patients with CWP syndromes. The anxiety-like behaviors were evaluated using the open field and elevated plus maze tests, and depression-like behaviors were measured by the forced swimming, sucrose consumption, and sucrose preference tests. The pain group receiving acidic saline displayed significantly lower paw withdrawal thresholds for 4weeks than animals in the vehicle group after repetitive intramuscular injections. The pain group showed a significantly shorter duration of exploring the central zone of the open field and the open arms of the elevated plus maze compared to the vehicle group. The pain group had a significantly lower preference for and consumption of the hedonic sucrose. Moreover, rats with chronic pain showed significantly longer immobility than the vehicle group in the forced swimming test. The results indicate that psychiatric behaviors are exacerbated in the CWP model. This study provides evidence for the validity of the acid-induced pain model analogous to patients with CWP syndromes. PMID:24726391

  11. Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme biosynthesis activity.

    Science.gov (United States)

    Gupta, Vipul; Liu, Shujie; Ando, Hideki; Ishii, Ryohei; Tateno, Shumpei; Kaneko, Yuki; Yugami, Masato; Sakamoto, Satoshi; Yamaguchi, Yuki; Nureki, Osamu; Handa, Hiroshi

    2013-12-01

    Salicylic acid is a classic nonsteroidal anti-inflammatory drug. Although salicylic acid also induces mitochondrial injury, the mechanism of its antimitochondrial activity is not well understood. In this study, by using a one-step affinity purification scheme with salicylic acid-immobilized beads, ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in mitochondria, was identified as a new molecular target of salicylic acid. Moreover, the cocrystal structure of the FECH-salicylic acid complex was determined. Structural and biochemical studies showed that salicylic acid binds to the dimer interface of FECH in two possible orientations and inhibits its enzymatic activity. Mutational analysis confirmed that Trp301 and Leu311, hydrophobic amino acid residues located at the dimer interface, are directly involved in salicylic acid binding. On a gel filtration column, salicylic acid caused a shift in the elution profile of FECH, indicating that its conformational change is induced by salicylic acid binding. In cultured human cells, salicylic acid treatment or FECH knockdown inhibited heme synthesis, whereas salicylic acid did not exert its inhibitory effect in FECH knockdown cells. Concordantly, salicylic acid treatment or FECH knockdown inhibited heme synthesis in zebrafish embryos. Strikingly, the salicylic acid-induced effect in zebrafish was partially rescued by FECH overexpression. Taken together, these findings illustrate that FECH is responsible for salicylic acid-induced inhibition of heme synthesis, which may contribute to its antimitochondrial and anti-inflammatory function. This study establishes a novel aspect of the complex pharmacological effects of salicylic acid.

  12. Tiagabine: efficacy and safety in partial seizures – current status

    Directory of Open Access Journals (Sweden)

    Jürgen Bauer

    2008-09-01

    Full Text Available Jürgen Bauer, Déirdre Cooper-MahkornDepartment of Epileptology, Bonn University Hospital, GermanyAbstract: Tiagabine hydrochloride (TGB is a selective gamma-aminobutyric acid (GABA reuptake inhibitor. TGB is effective as an add-on medication in adults and children 12 years and older in the treatment of partial seizures. Results of nonrandomized add-on trials with TGB show treatment success with seizure reduction of at least 50% in 33% to 46% of patients. In newly diagnosed patients with partial epilepsy, TGB monotherapy was as effective as carbamazepine. Comedication with TGB elevates the risk of nonconvulsive status (7.8% vs 2.7% without TGB. The most common side effects include dizziness/lightheadedness, asthenia/lack of energy and somnolence. TGB has no negative effects on cognition; it does not increase the risk of fractures or rash. TGB may interfere with color perception. TGB presents an intermediate risk for depression in patients with epilepsy (approximately 4%. Regarding the risk of overdose, 96–680 mg TGB (mean 224 mg caused seizures or coma. TGB is an antiepileptic drug exhibiting a specific anticonvulsive mechanism of action, the efficacy of which is relatively low when used in comedication. Critical side effects, such as the induction of nonconvulsive status epilepticus, further limit its use.Keywords: epilepsy, tiagabine, antiepileptic drugs, status epilepticus, pharmacotherapy

  13. Effect of Tanshitone on prevention and treatment of retinoic acid-induced osteoporosis in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yan-meng; LIU Yu-bo; GAO Yun-sheng

    2008-01-01

    Objective To observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice. Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after mice were given TAN at the dose of 40, 80, 160 mg·kg-1 respectively. Results Tanshitone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group. Conclusions Tanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

  14. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  15. Changes of GABA A Receptor α1 Subunit mRNA and [3H] Flunirazepam Binding in Animal Model of Status Epileptic Rats

    Institute of Scientific and Technical Information of China (English)

    Qinchi Lu

    2000-01-01

    OBJECTIVE: In the present study, we determinded whether status epilepticus or prolonged limbic seizures ( induced by pilocarpine) altered GABA A receptor αl subunit gene expression m the hippocanpus. BACKGROUND: A decrease in GABAergic inhibition during epileptogenesis plays an imprortant role in the development of persistent hyperexcitability observed during chronic epilepsy. METHODS: Stares epilepticus was reduced in male adult rats by a single i.p. injection ofpilocarpine (320-340 mg/kg). Rats that survived status epilepticus ( definded as continous seizure activity in the EcoG for at least 40 min) for 1 h and 2 h were sacrificed for GABA A receptor gene expression and binding assay. In situ hybridization was used to measure regional mRNA levels, and [3H] flunirazepam used to label the benzodiazepine binding sites. RESULTS: We found that 2h after the onset of seizure, GABA A receptor α1 m RNA decresed significarntly in the CA1 and CA3 fields of hippocampus. No significant change in ctl mRNA was observed in the dentate gyrus. However, [3H] flunirazepam binding decreased uniformly in CA l, CA3 and dentate gyrus 2h after status epfileptius. 1 h ofcontinuous seizures did not produce any significant change in either αl mRNA or [3H] flunirazepam birding in any of the hippocampal regions studied. Cresyl violet staining of the brain hippocampus areas lh or 2h after the seizure-onset. DISCUSSION: The above changes make the brain more susceptible for the development of chronic epilepsy. CONCLUSION: These results suggest that status epilepticus-induced decreased in GABA A recepor αl gene expression and [3H] flunirazepam binding in the hippocampus.

  16. Practice parameters in management of status epileptics

    Directory of Open Access Journals (Sweden)

    Usha Kant Misra

    2014-01-01

    Full Text Available Status epilepticus (SE is an emergency neurological problem, more common in the developing countries due to high incidence of infection, stroke and head injury. The protocol for management of SE is intravenous benzodiazepine, followed by phenytoin, valproate (VPA and phenobarbitone and if uncontrolled general anesthesia (GA. World Federation of Neurology recommends special guidelines for resource poor countries. Use of GA results in hypotension and respiratory depression needing intensive care management. There is a paucity of intensive care facilities hence the recommended antiepileptic drugs (AEDs which have inherent toxicity of hypotension and respiratory failure cannot be given safely. Under these situations AEDs such as VPA, levetiracetam and lacosamide may be evaluated in SE because of cardiovascular and respiratory safety profile. In this review, the limitations of existing guidelines in the developing countries have been discussed and a way forward has been suggested.

  17. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    Science.gov (United States)

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema.

  18. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    Science.gov (United States)

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema. PMID:7480214

  19. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J;

    2001-01-01

    The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mi...

  20. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    Directory of Open Access Journals (Sweden)

    Go Taniguchi

    2015-01-01

    All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each, impaired consciousness appeared. Electroencephalography (EEG showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

  1. Transgenic overexpression of 14-3-3 zeta protects hippocampus against endoplasmic reticulum stress and status epilepticus in vivo.

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    Gary P Brennan

    Full Text Available 14-3-3 proteins are ubiquitous molecular chaperones that are abundantly expressed in the brain where they regulate cell functions including metabolism, the cell cycle and apoptosis. Brain levels of several 14-3-3 isoforms are altered in diseases of the nervous system, including epilepsy. The 14-3-3 zeta (ζ isoform has been linked to endoplasmic reticulum (ER function in neurons, with reduced levels provoking ER stress and increasing vulnerability to excitotoxic injury. Here we report that transgenic overexpression of 14-3-3ζ in mice results in selective changes to the unfolded protein response pathway in the hippocampus, including down-regulation of glucose-regulated proteins 78 and 94, activating transcription factors 4 and 6, and Xbp1 splicing. No differences were found between wild-type mice and transgenic mice for levels of other 14-3-3 isoforms or various other 14-3-3 binding proteins. 14-3-3ζ overexpressing mice were potently protected against cell death caused by intracerebroventricular injection of the ER stressor tunicamycin. 14-3-3ζ overexpressing mice were also potently protected against neuronal death caused by prolonged seizures. These studies demonstrate that increased 14-3-3ζ levels protect against ER stress and seizure-damage despite down-regulation of the unfolded protein response. Delivery of 14-3-3ζ may protect against pathologic changes resulting from prolonged or repeated seizures or where injuries provoke ER stress.

  2. Genetic Deletion of the Neuronal Glutamate Transporter, EAAC1, Results in Decreased Neuronal Death after Pilocarpine-Induced Status Epilepticus

    OpenAIRE

    Lane, Meredith C.; Jackson, Joshua G.; Krizman, Elizabeth N.; Rothstein, Jeffery D.; Porter, Brenda E.; Robinson, Michael B.

    2013-01-01

    Excitatory amino acid carrier 1 (EAAC1, also called EAAT3) is a Na+-dependent glutamate transporter expressed by both glutamatergic and GABAergic neurons. It provides precursors for the syntheses of glutathione and GABA and contributes to the clearance of synaptically released glutamate. Mice deleted of EAAC1 are more susceptible to neurodegeneration in models of ischemia, Parkinson’s disease, and aging. Antisense knock-down of EAAC1 causes an absence seizure-like phenotype. Additionally, EAA...

  3. Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.

    Science.gov (United States)

    Choi, Yun-Sik; Lee, Boyoung; Hansen, Katelin F; Aten, Sydney; Horning, Paul; Wheaton, Kelin L; Impey, Soren; Hoyt, Kari R; Obrietan, Karl

    2016-09-01

    Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian homolog of the Aspergillus nidulans nuclear distribution molecule NudE. NDEL1 plays a critical role in neuronal migration, neurite outgrowth and neuronal positioning during brain development; however within the adult central nervous system, limited information is available regarding NDEL1 expression and functions. Here, the goal was to examine inducible NDEL1 expression in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain, including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression was principally localized to perikarya. Using a combination of immunolabeling and RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm. Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding protein (CREB) binding site within the CpG island proximal to the NDEL1 gene, and in vivo transgenic repression of CREB led to a marked downregulation of seizure-evoked NDEL1 expression. Together these data indicate that NDEL1 is inducibly expressed in the adult nervous system, and that signaling via the CREB/CRE transcriptional pathway is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth during development raises the interesting prospect that inducible NDEL1 in the mature nervous system could contribute to the well-characterized structural and functional plasticity resulting from repetitive seizure activity. PMID:27298008

  4. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells

    Science.gov (United States)

    Cao, Weibiao

    2016-01-01

    Mechanisms of the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA. PMID:26901778

  5. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  6. Effect of partial liquid ventilation on oleic acid-induced inflammatory responses in piglets

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; WANG Qiang; LIU Ying-long; LI Xiao-feng; LI Jian-an; L(U) Xiao-dong; LING Feng; LIU Ai-jun; FAN Xiang-ming

    2010-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury (ALI) in children often results in a high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced to develop ALI by oleic acid.The animals were randomly assigned to two groups (n=6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group.Results Compared with MV group, PLV group got better cardiopulmonary variables (P <0.05).These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2).Partial liquid ventilation reduced IL-1β, IL-6, IL-10 and TN F-α both in plasma and tissue concentrations compared with MV group (P <0.05).Conclusions Partial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.

  7. Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse.

    Science.gov (United States)

    Calvet, J P; Chadwick, L J

    1994-12-01

    Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.

  8. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

    Directory of Open Access Journals (Sweden)

    Qin Lan

    2011-12-01

    Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

  9. Neuroprotective effects of MK-801 on L-2-chloropropionic acid-induced neurotoxicity.

    Science.gov (United States)

    Williams, R E; Lock, E A; Bachelard, H S

    2001-02-01

    L-2-Chloropropionic acid is selectively toxic to the cerebellum in rats; the granule cell necrosis observed within 48 h can be prevented by prior administration of MK-801. Short-term treatment (2 h) with L-2-chloropropionic acid has also been shown to activate the mitochondrial pyruvate dehydrogenase complex in fasted adult rats. This study aimed to investigate the effect of prior exposure to MK-801 on the biochemical and neurotoxicological effects of L-2-chloropropionic acid. Extracts were prepared from the forebrain and cerebellum of animals that had been treated with L-2-chloropropionic acid, with and without prior treatment with MK-801, and were analysed using magnetic resonance spectroscopy and amino acid analysis. Glucose metabolism was studied by monitoring the metabolism of [1-(13)C]-glucose using GC/MS. L-2-Chloropropionic acid caused increased glucose metabolism in both brain regions 6 h after administration, confirming activation of the pyruvate dehydrogenase complex, which was not prevented by MK-801. After 48 h an increase in lactate and a decrease in N-acetylaspartate was observed only in the cerebellum, whereas phosphocreatine and ATP decreased in both tissues. MK-801 prevented the changes in lactate and N:-acetylaspartate, but not those on the energy state. These studies suggest that L-2-chloropropionic acid-induced neurotoxicity is only partly mediated by the NMDA subtype of glutamate receptor.

  10. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    Science.gov (United States)

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola.

  11. Synergistic action of famotidine and chlorpheniramine on acetic acid-induced chronic gastric ulcer in rats

    Institute of Scientific and Technical Information of China (English)

    Zhen Qin; Chao Chen

    2005-01-01

    AIM: To assess the synergistic action of famotidine (FMD)and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.METHODS: Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n= 8), CPA group (n = 8), and FMD+CPA group (n = 8).Each group was given intraperitoneally (i.p.) 0.5 mL/100g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively,daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenation was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF1a)and IL-8 were determined by radioimmunoassay.RESULTS: The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF1a and MPO were confirmed.The effect of FMlD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm2) was reduced from 40.18±2.6 in control group to 6.83±2.97 in PMD+CPA group, P<0.01, and from 32.9±3.27 in FMD group to 6.83±2.97 in pMlD+CPA group,P<0.01. The plasma levels of IL-8 decreased from 0.69±0.11 ng/L in control group to 0.4±0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51±0.08 ng/L in FMD group to 0.4±0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF1a increased from 7.55±1.65 ng/L in control group to 16.62±0.97 ng/L in PMD+CPA group, P<0.01,and from 13.15±1.48 ng/L in FMD group to 16.62±0.97ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12±2.05 u/Lin control group to 4.33±0.95 u/L in PMD+CPA group,P<0.01, and from 8.3±1.29 u/L in FMD group to 4.33±0.95 u/L, P<0.01.CONCLUSION: The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the

  12. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  13. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  14. Mechanism of Ascorbic Acid-induced Reversion Against Malignant Phenotype in Human Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    YA-XUAN SUN; QIU-SHENG ZHENG; GANG LI; DE-AN GUO; ZI-REN WANG

    2006-01-01

    Objective To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid. Methods Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid(TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H2O2 were evaluated by spectrophotography. Results Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 μm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 μm·s-1·V-1·cm-1. The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H2O2) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H2O2 group. Conclusions Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

  15. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    International Nuclear Information System (INIS)

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  16. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    OpenAIRE

    Mohsen Minaiyan; Gholamreza Asghari; Diana Taheri; Mozhgan Saeidi; Salar Nasr-Esfahani

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups...

  17. Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism

    OpenAIRE

    Ji-Woon Kim; Hana Seung; Kyung Ja Kwon; Mee Jung Ko; Eun Joo Lee; Hyun Ah Oh; Chang Soon Choi; Ki Chan Kim; Edson Luck Gonzales; Jueng Soo You; Dong-Hee Choi; Jongmin Lee; Seol-Heui Han; Sung Min Yang; Jae Hoon Cheong

    2014-01-01

    Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). W...

  18. Comparative Study of Berberis vulgaris Fruit Extract and Berberine Chloride Effects on Acetic Acid-Induced Colitis in Rats

    OpenAIRE

    Minaiyan, Mohsen; Ghannadi, Alireza; Mahzouni, Parvin; Jaffari-Shirazi, Elham

    2011-01-01

    Antioxidant and immunomodulatory effects of anthocyanins are abundant in berberry fruits suggesting that they may have beneficial effects on inflammatory bowel diseases (IBD). The present study was carried out to investigate the anti-colitic effect of Berberis vulgaris fruit extract (BFE) compared to berberine chloride (BEC) and corticosteroids using an animal model of acetic acid induced experimental colitis. BFE with three different doses (375, 750, and 1500 mg/Kg) was administered orally o...

  19. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells

    OpenAIRE

    Qin, Ying; NAITO, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko

    2011-01-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intest...

  20. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  1. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    Science.gov (United States)

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects.

  2. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    the cranium and abnormal changes of the metencephalon and face.cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of NekT, Igfbp5, Zw10,Csf3r, Psmc6 and Rbl, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting.CONCLUSION: Cdk5, NekT, Igfbp5, ZwlO, Csf3r, Psmc6, Rb 1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.

  3. Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets

    Institute of Scientific and Technical Information of China (English)

    LING Feng; LIU Ying-long; LIU Ai-jun; WANG Dong; WANG Qiang

    2011-01-01

    Background Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.Methods Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n=5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.Results Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio,partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P<0.05or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P<0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P<0.05).Conclusions Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

  4. Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.

    Science.gov (United States)

    Gustavsson, F; Glantz, M; Poulsen, N A; Wadsö, L; Stålhammar, H; Andrén, A; Lindmark Månsson, H; Larsen, L B; Paulsson, M; Fikse, W F

    2014-01-01

    Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and

  5. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    Science.gov (United States)

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

  6. Modulation of the retinoic acid-induced cell apoptosis and differentiation by the human TR4 orphan nuclear receptor

    International Nuclear Information System (INIS)

    In our previous studies, the TR4 orphan nuclear receptor (TR4) has been demonstrated to suppress retinoic acid (RA)-induced transactivation via a negative feedback control mechanism and in situ analysis showed that TR4 is extensively expressed in mouse brain, especially in regions where the cells are proliferating. To further study the potential roles of TR4 during cell differentiation, a tetracycline-inducible system with anti-sense TR4 in teratocarcinoma P19 cell lines was generated to analyze the retinoic acid-induced differentiation of these cells. The results indicated that the expression of TR4 reduced by doxycycline anti-sense TR4 would alter the retinoic acid-induced differentiation pathway that results in the changes of cell morphology and cell cycle profile. Unexpectedly, our data further indicated that the RA-induced apoptosis, judging by DNA fragmentation, could also be altered by the induction of anti-sense TR4. Together, these findings provide the first in vivo evidence that an orphan nuclear receptor, such as TR4, may play major roles in the RA-mediated apoptosis or differentiation in P19 cells

  7. Saturated Fatty Acid Induces Insulin Resistance Partially Through Nucleotide-binding Oligomerization Domain 1 Signaling Pathway in Adipocytes

    Institute of Scientific and Technical Information of China (English)

    Yi-jun Zhou; Yin-si Tang; Yu-ling Song; Ai Li; Hui Zhou; Yan Li

    2013-01-01

    Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.

  8. Olodaterol attenuates citric acid-induced cough in naïve and ovalbumin-sensitized and challenged guinea pigs.

    Science.gov (United States)

    Wex, Eva; Bouyssou, Thierry

    2015-01-01

    Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known.

  9. Combinatorial localized dissolution analysis: Application to acid-induced dissolution of dental enamel and the effect of surface treatments.

    Science.gov (United States)

    Parker, Alexander S; Al Botros, Rehab; Kinnear, Sophie L; Snowden, Michael E; McKelvey, Kim; Ashcroft, Alexander T; Carvell, Mel; Joiner, Andrew; Peruffo, Massimo; Philpotts, Carol; Unwin, Patrick R

    2016-08-15

    A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca(2+) flux ( [Formula: see text] ), is first order with respect to the interfacial proton concentration and given by the following rate law: [Formula: see text] , with k0=0.099±0.008cms(-1). Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10-20nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient. PMID:27209395

  10. Combinatorial localized dissolution analysis: Application to acid-induced dissolution of dental enamel and the effect of surface treatments.

    Science.gov (United States)

    Parker, Alexander S; Al Botros, Rehab; Kinnear, Sophie L; Snowden, Michael E; McKelvey, Kim; Ashcroft, Alexander T; Carvell, Mel; Joiner, Andrew; Peruffo, Massimo; Philpotts, Carol; Unwin, Patrick R

    2016-08-15

    A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca(2+) flux ( [Formula: see text] ), is first order with respect to the interfacial proton concentration and given by the following rate law: [Formula: see text] , with k0=0.099±0.008cms(-1). Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10-20nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient.

  11. Antiperoxidative and antiinflammatory effect of Sida cordifolia Linn. on quinolinic acid induced neurotoxicity.

    Science.gov (United States)

    Swathy, S S; Panicker, Seema; Nithya, R S; Anuja, M M; Rejitha, S; Indira, M

    2010-09-01

    Sida cordifolia is a plant belonging to the Malvaceae family used in many ayurvedic preparations. This study aimed at assessing the effects of ethanolic extract of Sida cordifolia root on quinolinic acid (QUIN) induced neurotoxicity and to compare its effect with the standard drug deprenyl in rat brain. Rats were divided into six groups: (1) control group (2) QUIN (55 microg/100 g bwt/day) (3) 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (4) Deprenyl (100 microg/100 g bwt/day) (5) QUIN (55 microg/100 g bwt/day) + 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (6) QUIN (55 microg/100 g bwt/day) + Deprenyl (100 microg/100 g bwt/day). At the end of the experimental period a status of lipid peroxidation products, protein peroxidation product, activities of the scavenging enzymes and the activities of the inflammatory markers were analyzed. Results revealed that the lipid peroxidation products decreased and the activities of the scavenging enzymes increased significantly in the brain of the plant extract treated group, deprenyl treated group and also in the coadminstered groups. The activities of markers of inflammatory responses such as cyclooxygenase and lipoxygenase were found to be significantly increased in the QUIN treated rats and this was decreased upon the administration of plant extract and deprenyl. In short, the study revealed that 50% ethanolic extract of Sida cordifolia has got potent antioxidant and antiinflammatory activity and the activity is comparable with the standard drug deprenyl.

  12. 76 FR 34968 - Notice of Availability for Exclusive, Non-Exclusive, or Partially-Exclusive Licensing of an...

    Science.gov (United States)

    2011-06-15

    ... of an Invention Concerning the Methods and Compositions for Treating Status Epilepticus and Seizures Causing Status Epilepticus AGENCY: Department of the Army, DoD. ACTION: Notice. SUMMARY: Announcement is... ``Methods and Compositions for Treating Status Epilepticus and Seizures Causing Status Epilepticus''...

  13. Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Sergey V Popov; Pavel A Markov; Ida R Nikitina; Sergey Petrishev; Vasily Smirnov; Yury S Ovodov

    2006-01-01

    AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis.METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4%Evans blue passage after i.p. injection of 0.05 mol/L acetic acid.RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P < 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P < 0.01)were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P < 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P < 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P < 0.01).OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P < 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50vs 235 ± 37, P < 0.05).CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP,on acetic acid-induced colitis in mice was detected.A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.

  14. Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic acid-inducible gene- like receptors, which synergize to induce type I interferon production

    DEFF Research Database (Denmark)

    Rasmussen, Simon Brandtoft; Jensen, Søren B; Nielsen, C;

    2009-01-01

    The innate antiviral response is initiated by pattern recognition receptors, which recognize viral pathogen-associated molecular patterns. Here we show that retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) in cooperation with Toll-like receptor (TLR) 9 is required for expression of type...

  15. Chromosomal localization of a novel retinoic acid induced gene RA28 and the protein distribution of its encoded protein

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Gene RA28 is a retinoic acid induced novel gene isolated in our laboratory previously. All-trans retinoic acid (ATRA) was used to induce lung adenocarcinoma cell line GLC-82, and RA28 was obtained by subtractive hybridization. Green fluorescent protein (GFP) has emerged as a unique tool for examining introcellular phenomena in living cells. GFP possesses an intrinsic fluorescence at 488 nm that does not require other co-factors. In this report, an eukaryotic expression plasmid pEGFP-C1-RA28 was constructed and transfected with parental cell line GLC-82 to analyze protein expression and its distribution in living cells. Moreover, radiation hybrid (RH) technique was used to localize RA28 to the chromosome. The results show that gene RA28 is mapped to the chromosome 19q13.1 region, its encoded protein is distributed on cell membrane. All the results further demonstrate that GFP and RH techniques are accurate, fast, repetitive, and will be powerful methods for investigating the gene and protein localization.

  16. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Science.gov (United States)

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity.

  17. Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia chebula on Citric Acid-Induced Cough

    Science.gov (United States)

    Chatterjee, Udipta Ranjan; Majee, Sujay Kumar; Ray, Bimalendu

    2013-01-01

    Terminalia chebula, a medicinal plant, is widely used in the management of various diseases. As the water extract of its dried ripe fruit is a frequently used preparation, we decided to look for bioactive polysaccharide in this extract. We demonstrate that the obtained polysaccharide fraction, CP, contained a highly branched arabinogalactan protein having a (1 → 3)-, (1 → 6)- and (1 → 3, 6)-linked β-D-Galp together with (1 → 5)- and (1 → 3)-linked α-L-Araf and nonreducing end units of α-L-Araf. This polymer possesses strong antitussive property. Our results showed that the number of citric acid-induced cough efforts decreased significantly after the oral application of polysaccharide fraction in a dose of 50 mg kg−1 body weight. Its antitussive efficacy was higher than cough suppressive effect of standard drug codeine. Therefore, traditional aqueous extraction method provides a major polysaccharide, which induces a pharmacological effect: this could represent an attractive approach in phytotherapeutic managements. PMID:23878602

  18. Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia chebula on Citric Acid-Induced Cough

    Directory of Open Access Journals (Sweden)

    Gabriela Nosalova

    2013-01-01

    Full Text Available Terminalia chebula, a medicinal plant, is widely used in the management of various diseases. As the water extract of its dried ripe fruit is a frequently used preparation, we decided to look for bioactive polysaccharide in this extract. We demonstrate that the obtained polysaccharide fraction, CP, contained a highly branched arabinogalactan protein having a 1→3-, 1→6- and 1→3,6-linked β-D-Galp together with 1→5- and 1→3-linked α-L-Araf and nonreducing end units of α-L-Araf. This polymer possesses strong antitussive property. Our results showed that the number of citric acid-induced cough efforts decreased significantly after the oral application of polysaccharide fraction in a dose of 50 mg kg−1 body weight. Its antitussive efficacy was higher than cough suppressive effect of standard drug codeine. Therefore, traditional aqueous extraction method provides a major polysaccharide, which induces a pharmacological effect: this could represent an attractive approach in phytotherapeutic managements.

  19. Protective Effect of Cod (Gadus macrocephalus) Skin Collagen Peptides on Acetic Acid-Induced Gastric Ulcer in Rats.

    Science.gov (United States)

    Niu, Huina; Wang, Zhicong; Hou, Hu; Zhang, Zhaohui; Li, Bafang

    2016-07-01

    This research was performed to explore the protective effect of cod skin collagen peptides (CCP) on gastric ulcer induced by acetic acid. The CCP were fractionated into low molecular CCP (LMCCP, Mw 3 kDa). In HMCCP and LMCCP, glycine of accounted for about one-third of the total amino acids without cysteine and tryptophan, and hydrophobic amino acids accounted for about 50%. After 21 d CCP treatment (60 or 300 mg/kg, p.o./daily), the healing effects on acetic acid-induced gastric ulcers were evaluated by macroscopic measure, microscopic measure, and immune histochemistry. Moreover, the expression levels of the growth factors, such as vascular endothelial growth factor, epidermal growth factor, transforming growth factor β1 (TGFβ1), and the heat shock protein 70 (HSP70) was detected. The results showed that both LMCCP and HMCCP could significantly decrease the ulcer areas and promote the healing of the lesions. They also could improve the levels of hexosamine, glutathione, superoxide dismutase, and glutathione peroxidase, and reduce the content of malondialdehyde and inducible nitric oxide synthase. In addition, the expression level of TGFβ1 gene and HSP70 mRNA was significantly improved by the treatment. It suggested that CCP could be able to improve symptoms of gastric ulcer and probably be used in the treatment of gastric ulcer. PMID:27219644

  20. Biocontrol agents-mediated suppression of oxalic acid induced cell death during Sclerotinia sclerotiorum-pea interaction.

    Science.gov (United States)

    Jain, Akansha; Singh, Akanksha; Singh, Surendra; Sarma, Birinchi Kumar; Singh, Harikesh Bahadur

    2015-05-01

    Oxalic acid (OA) is an important pathogenic factor during early Sclerotinia sclerotiorum-host interaction and might work by reducing hydrogen peroxide production (H2 O2 ). In the present investigation, oxalic acid-induced cell death in pea was studied. Pea plants treated with biocontrol agents (BCAs) viz., Pseudomonas aeruginosa PJHU15, Bacillus subtilis BHHU100, and Trichoderma harzianum TNHU27 either singly and/or in consortium acted on S. sclerotiorum indirectly by enabling plants to inhibit the OA-mediated suppression of oxidative burst via induction of H2 O2 . Our results showed that BCA treated plants upon treatment with culture filtrate of the pathogen, conferred the resistance via. significantly decreasing relative cell death of pea against S. sclerotiorum compared to control plants without BCA treatment but treated with the culture filtrate of the pathogen. The results obtained from the present study indicate that the microbes especially in consortia play significant role in protection against S. sclerotiorum by modulating oxidative burst and partially enhancing tolerance by increasing the H2 O2 generation, which is otherwise suppressed by OA produced by the pathogen.

  1. Phenylbutyric acid induces the cellular senescence through an Akt/p21{sup WAF1} signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hag Dong [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of); Jang, Chang-Young [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Choe, Jeong Min [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of); Department of Biochemistry, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705 (Korea, Republic of); Sohn, Jeongwon, E-mail: biojs@korea.ac.kr [Department of Biochemistry, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705 (Korea, Republic of); Kim, Joon, E-mail: joonkim@korea.ac.kr [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer Phenylbutyric acid induces cellular senescence. Black-Right-Pointing-Pointer Phenylbutyric acid activates Akt kinase. Black-Right-Pointing-Pointer The knockdown of PERK also can induce cellular senescence. Black-Right-Pointing-Pointer Akt/p21{sup WAF1} pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21{sup WAF1} induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21{sup WAF1} pathway by PERK inhibition.

  2. Standardized Extract of Bacopa monniera Attenuates Okadaic Acid Induced Memory Dysfunction in Rats: Effect on Nrf2 Pathway

    Directory of Open Access Journals (Sweden)

    Subhash Dwivedi

    2013-01-01

    Full Text Available The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer and Melatonin (an antioxidant on nuclear factor erythroid 2 related factor 2 (Nrf2 pathway in Okadaic acid induced memory impaired rats. OKA (200 ng was administered intracerebroventricularly (ICV to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg and Melatonin (20 mg/kg were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats.

  3. Inhibition of acid-induced apoptosis by targeting ASIC1a mRNA with short hairpin RNA

    Institute of Scientific and Technical Information of China (English)

    Xie-chuan WENG; Jian-quan ZHENG; Qing-e JIN; Xiao-yun MA

    2007-01-01

    Aim: To study the role of acid-sensing ion channel (ASIC) la in the cell death and apoptosis induced by extracellular acid in C6 glioma cells. Methods: The stable ASICla-silenced C6 cell line, built with RNA interference technology, were con-firmed by RT-PCR and Western blot analysis. The cell viability following acid exposure was analyzed with lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The apoptotic cells dyed with Annexin-V and propidium iodide were measured with a flow cytometer, while the changes of cell cycle were also assayed. Results: The downregulation of ASIC 1 a proteins by stable transfection of short hairpin RNA decreased the cell death percentage and increased cell viability following acid exposure with LDH and the MTT assay. The rate of apoptosis was lower in the ASIC la-silenced cell line than that in the wild-type C6 cell line. The percentage of sub-G0 cells was lower in the ASICla-silenced C6 cells than that in the wild-type cells. Conclusion: Extracellular acid induced cell death and apoptosis viaASICla mechanisms in the C6 glioma cells.

  4. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2014-02-01

    Full Text Available Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE and its chloroform fraction (MCF on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4% and continued for 5 days. Prednisolone (4 mg/kg and normal saline (1 ml/kg were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6 and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive.

  5. Priming by Hexanoic acid induce activation of mevalonic and linolenic pathways and promotes the emission of plant volatiles.

    Directory of Open Access Journals (Sweden)

    Eugenio eLlorens

    2016-04-01

    Full Text Available Hexanoic acid is a short natural monocarboxylic acid present in some fruits and plants. Previous studies reported that soil drench application of this acid induces effective resistance in tomato plants against Botrytis cinerea and Pseudomonas syringae and in citrus against Alternaria alternata and Xanthomonas citri. In this work, we performed an in deep study of the metabolic changes produced in citrus by the application of hexanoic acid in response to the challenge pathogen Alternaria alternata, focusing on the response of the plant. Moreover, we used 13C labeled hexanoic to analyze its behavior inside the plants. Finally, we studied the volatile emission of the treated plants after the challenge inoculation. Drench application of 13C labeled hexanoic demonstrated that this molecule stays in the roots and is not mobilized to the leaves, suggesting long distance induction of resistance. Moreover, the study of the metabolic profile showed an alteration of more than two hundred molecules differentially induced by the application of the compound and the inoculation with the fungus. Bioinformatics analysis of data showed that most of these altered molecules could be related with the mevalonic and linolenic pathways suggesting the implication of these pathways in the induced resistance mediated by hexanoic acid. Finally, the application of this compound showed an enhancement of the emission of 17 volatile metabolites. Taken together, this study indicates that after the application of hexanoic acid this compound remains in the roots, provoking molecular changes that may trigger the defensive response in the rest of the plant mediated by changes in the mevalonic and linolenic pathways and enhancing the emission of volatile compounds, suggesting for the first time the implication of mevalonic pathway in response to hexanoic application.

  6. Protective effect of the methanolic extract of malva parviflora l. leaves on acetic acid-induced ulcerative colitis in rats

    Directory of Open Access Journals (Sweden)

    Aisha Dugani

    2016-01-01

    Full Text Available Background/Aims: Inflammatory bowel disease (IBD is a general term describing chronic, idiopathic relapsing, inflammatory conditions of the gastrointestinal tract of unknown etiology. Previous studies have indicated that Malva parviflora leaf extract possesses anti-inflammatory, antioxidant, and antiulcerogenic activity. activity. This work aimed to investigatee the anti-inflammatory effect of the methanolic (MEMP and aqueous (AEMP extracts of M. parviflora leaves on acetic acid-induced colitis in rats. Materials and Methods: 42 male Wistar albino rats were divided into seven groups (n = 6. Group I: Normal saline control group with no colitis; Group II: Acetic acid colitis group; Group III: 100 mg/kg/5 d MEMP; Group IV: 200 mg/kg/5 d.MEMP; Group V: 100 mg/kg/5 d AEMP; Group VI: 200 mg/kg/5 d AEMP; Group VII: Prednisolone group (2 mg/kg/5 d. Treatments were followed by induction of colitis using intrarectal instillation of 2 mL of 4% acetic acid. Colon damage was evaluated macroscopically (spleen weight/body weight, colon weight/length ratio and the histological changes were also recorded. Results: The results of this study showed that acetic acid caused severe inflammation of the colon and a significant increase in spleen weight/body weight, and an increase in colon weight/length ratio compared with normal control group. Pretreatment with MEMP and AEMP for 5 days followed by induction of colitis resulted in a significant attenuation of spleen weight and colon weight/length ratio compared with acetic acid control group. Methanolic extract provided better anticolitic effect than aqueous extract; the effect was prominent at the dose of 200 mg/kg. Histopathological findings confirmed the protective effect of the MEMP. Conclusion: In conclusion, MEMP could ameliorate mucosal damage in experimentally induced colitis when given orally.

  7. Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.

    Directory of Open Access Journals (Sweden)

    Ji-Woon Kim

    Full Text Available Autism spectrum disorder (ASD is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model. We found that prenatal exposure of valproic acid (VPA induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.

  8. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    Directory of Open Access Journals (Sweden)

    F Aura Kullmann

    Full Text Available Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5% to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion was precisely repeated every 30 minutes. Administration of vehicle (saline i.v. occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v. after the 8(th. Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function.

  9. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    Science.gov (United States)

    Kullmann, F Aura; Wells, Grace I; Langdale, Christopher L; Zheng, Jihong; Thor, Karl B

    2013-01-01

    Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion) was precisely repeated every 30 minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after the 8(th). Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function. PMID:24040064

  10. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-LI adipocytes.METHODS:The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium.Berberine treatment was performed at the same time.Glucose uptake rate was determined by the 2-deoxy-[3H]-Dglucose method.The levels of IkB kinase beta (IKKβ)Ser181 phosphorylation,insulin receptor substrate1(IRS-1) Ser307 phosphorylation,expression of IKKβ,IRS-1,nuclear transcription factor kappaB p65 (NF-κB p65),phosphatidylinositol-3-kinase p85(PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting.The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy(CLSM).RESULTS:After the intervention of palmic acid for 24 h,the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%.Meanwhile,the expression of IRS-1 and PI-3K p85 protein was reduced,while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation,and nuclear translocation of NF-κB p65 protein were increased.However,the above indexes,which indicated the existence of insulin resistance,were reversed by berberine although the expression of GLUT4,IKKβ and total NF-κB p65 protein were not changed during this study.CONCLUSION:Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine.Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.

  11. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation.

    Science.gov (United States)

    Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Koike, Marcia Kiyomi; Cintra, Dennys Esper; Ferreira, Fabiana Dias; Nunes, Valeria Sutti; Castilho, Gabriela; Gioielli, Luiz Antonio; Paula Bombo, Renata; Catanozi, Sergio; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Passarelli, Marisa; Nakandakare, Edna Regina; Lottenberg, Ana Maria

    2016-06-01

    Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.

  12. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    OpenAIRE

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat p...

  13. Palmitic acid induces interleukin-1β secretion via NLRP3 inflammasomes and inflammatory responses through ROS production in human placental cells.

    Science.gov (United States)

    Shirasuna, Koumei; Takano, Hiroki; Seno, Kotomi; Ohtsu, Ayaka; Karasawa, Tadayoshi; Takahashi, Masafumi; Ohkuchi, Akihide; Suzuki, Hirotada; Matsubara, Shigeki; Iwata, Hisataka; Kuwayama, Takehito

    2016-08-01

    Maternal obesity, a major risk factor for adverse pregnancy complications, results in inflammatory cytokine release in the placenta. Levels of free fatty acids are elevated in the plasma of obese human. These fatty acids include obesity-related palmitic acids, which is a major saturated fatty acid, that promotes inflammatory responses. Increasing evidence indicates that nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasomes mediate inflammatory responses induced by endogenous danger signals. We hypothesized that inflammatory responses associated with gestational obesity cause inflammation. To test this hypothesis, we investigated the effect of palmitic acid on the activation of NLRP3 inflammasomes and inflammatory responses in a human Sw.71 trophoblast cell line. Palmitic acid stimulated caspase-1 activation and markedly increased interleukin (IL)-1β secretion in Sw.71 cells. Treatment with a caspase-1 inhibitor diminished palmitic acid-induced IL-1β release. In addition, NLRP3 and caspase-1 genome editing using a CRISPR/Cas9 system in Sw.71 cells suppressed IL-1β secretion, which was stimulated by palmitic acid. Moreover, palmitic acid stimulated caspase-3 activation and inflammatory cytokine secretion (e.g., IL-6 and IL-8). Palmitic acid-induced cytokine secretion were dependent on caspase-3 activation. In addition, palmitic acid-induced IL-1β, IL-6, and IL-8 secretion was depended on reactive oxygen species (ROS) generation. In conclusion, palmitic acid caused activation of NLRP3 inflammasomes and inflammatory responses, inducing IL-1β, IL-6, and IL-8 secretion, which is associated with ROS generation, in human Sw.71 placental cells. We suggest that obesity-related palmitic acid induces placental inflammation, resulting in association with pregnancy complications. PMID:27300134

  14. Stock Status

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These data inform the public of the most recent stock status for all stocks (FSSI and non-FSSI) in the fishery management unit contained in a fishery managment...

  15. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus

    Science.gov (United States)

    Shukitt-Hale, Barbara; Lau, Francis C.; Carey, Amanda N.; Galli, Rachel L.; Spangler, Edward L.; Ingram, Donald K.; Joseph, James A.

    2016-01-01

    Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and increased susceptibility to inflammatory insults. In the current study, we investigated whether polyphenols in blueberries can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed and total RNA from the hippocampus was extracted and used in real-time quantitative RT-PCR (qRT-PCR) to analyze the expression of inflammation-related genes. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1β and TNF-α, the neurotrophic factor IGF-1, and the transcription factor NF-κB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1β, TNF-α, and NF-κB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions

  16. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    Science.gov (United States)

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient acidification in both the experimental conditions, though pHi recovery was faster in 0% Ca2+ medium than that in 100% Ca2+ medium. In the presence of BAPTA, a calcium chelator, a rapid recovery of DHA-induced acidosis was observed. Furthermore, addition of CaCl2 into 0% Ca2+ medium curtailed DHA-evoked rapid pHi recovery. In 0% Ca2+ medium, containing BAPTA, DHA did not evoke increases in [Ca2+]i, though this fatty acid still induced a rapid acidification in these cells. These observations suggest that calcium is implicated in the long-lasting DHA-induced acidosis. DHA-induced rapid acidification may be due to its deprotonation in the plasma membrane (flip-flop model), as suggested by the following observations: (1) DHA with a –COOH group induced intracellular acidification, but this fatty acid with a –COOCH3 group failed to do so, and (2) DHA, but not propionic acid, -induced acidification was completely reversed by addition of fatty acid-free bovine serum albumin in these cells. These results suggest that DHA induces acidosis via deprotonation and Ca2+ mobilization in human T-cells. PMID:14645139

  17. Role of cranial imaging in epileptic status

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Pradeep P.; Kalita, Jayantee [Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014 (India); Misra, Usha K. [Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014 (India)], E-mail: drukmisra@rediffmail.com

    2009-06-15

    Introduction: There is paucity of studies evaluating the role of cranial imaging in the management of status epilepticus (SE); therefore this study evaluates the role of imaging in predicting the outcome of SE. Methods: Consecutive patients with SE were prospectively evaluated. Clinical evaluation, blood counts, serum chemistry and cerebrospinal fluid (CSF) were carried out. Cranial CT scan was performed on a spiral CT and MRI on a 1.5 T scanner. Patients were treated with IV sodium valproate, phenytoin and benzodiazepines as per fixed protocol. Outcome was defined as seizure control at 1 h and mortality. Various clinical and radiological parameters were correlated. Results: There were 99 patients with SE whose mean age was 35 (1-78) years, 40 females and 17 were below 12 years of age. Fifty six patients had central nervous system (CNS) infections, 15 strokes, 13 metabolic encephalopathy, 5 drug default and in the remaining 10 patients various acute symptomatic causes were present. Cranial imaging was abnormal in 59% patients. CT was abnormal in 21 (47.7%) out of 44 patients whereas MRI was abnormal in 26 (63.4%) out of 41 patients. Both MRI and CT were carried out in 14 patients and 12 revealed abnormalities; 2 had abnormality only on MRI. Imaging revealed cortical lesions in 10, subcortical in 19 and both cortical as well as subcortical in 30 patients. One hour seizure control was achieved in 60, seizures recurred within 24 h in 38 and 27 patients died during hospital stay. Seizure type, duration of SE, seizure control at 1 h and mortality did not correlate with radiological abnormalities. Conclusion: Cranial imaging reveals structural abnormality in 59% patients with SE and was not related to SE control and mortality.

  18. Neuronal acid-induced [Zn²⁺]i elevations calibrated using the low-affinity ratiometric probe FuraZin-1.

    Science.gov (United States)

    Kiedrowski, Lech

    2015-11-01

    The experiments were carried out on primary cultures of murine cortical neurons from cryopreserved preparations obtained from embryonic-day-16 fetuses. To calibrate acid-induced intracelluar [Zn(2+) ] ([Zn(2+) ]i ) elevations, a low affinity (Kd = 39 μM at pH 6.1) ratiometric Zn(2+) probe, FuraZin-1, was used. A pHi drop from 7.2 to 6.1 caused [Zn(2+) ]i elevations reaching 2 μM; when the thiol-reactive agent N-ethylmaleimide (NEM) was subsequently applied, [Zn(2+) ]i increased further to 5.6 μM; analogous acid- and NEM-induced [Zn(2+) ]i elevations could also be detected but not calibrated, using the high affinity Zn(2+) probe FluoZin-3. The data indicate that NEM causes Zn(2+) release from ligands that chelate Zn(2+) at pH 6.1. ATP could also chelate Zn(2+) at pH 6.1 because its pKa is about 6.8. Therefore, it was tested whether an ATP depletion affects the acid-induced [Zn(2+) ]i elevations. The ATP depletion was induced by inhibiting mitochondrial and glycolytic ATP production. Interestingly, an almost complete ATP depletion (confirmed using a luciferin/luciferase assay) failed to affect the acid-induced [Zn(2+) ]i increases. These data suggest that the total amount of Zn(2+) accumulated in intracellular ATP-dependent stores (Zn(2+) -ATP complexes and organelles that accumulate Zn(2+) in an ATP-dependent manner) is negligible compared to the amount of Zn(2+) accumulated in the acid-sensitive intracellular ligands. In vitro, upon acidification, Zn(2+) -cysteine complexes release Zn(2+) and ATP chelates the released Zn(2+) . However, in vivo (cultured neurons), an ATP depletion failed to enhance acid-induced [Zn(2+) ]i elevations. These [Zn(2+) ]i elevations were calibrated using a low affinity ratiometric probe FuraZin-1; they reached 2 µM levels and increased to 5 µM when a thiol-reactive agent, N-ethylmaleimide, compromised Zn(2+) binding by cysteines. PMID:26263185

  19. The role of amino acid-induced mammalian target of rapamycin complex 1(mTORC1) signaling in insulin resistance.

    Science.gov (United States)

    Yoon, Mee-Sup; Choi, Cheol Soo

    2016-01-01

    Mammalian target of rapamycin (mTOR) controls cell growth and metabolism in response to nutrients, energy, and growth factors. Recent findings have placed the lysosome at the core of mTOR complex 1 (mTORC1) regulation by amino acids. Two parallel pathways, Rag GTPase-Ragulator and Vps34-phospholipase D1 (PLD1), regulate mTOR activation on the lysosome. This review describes the recent advances in understanding amino acid-induced mTOR signaling with a particular focus on the role of mTOR in insulin resistance. PMID:27534530

  20. Compliance status

    Energy Technology Data Exchange (ETDEWEB)

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the activities conducted to ensure that the Hanford Site is in compliance with federal environmental protection statutes and related Washington State and local environmental protection regulations and the status of Hanford`s compliance with these requirements. Environmental permits required under the environmental protection regulations are discussed under the applicable statute.

  1. Oleanolic acid-induced apoptosis and its relation with intracellular calcium in human lung adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    Asmitanand; Thakur

    2010-01-01

    Objective To investigate the effect of oleanolic acid (OA) on apoptosis,correlation between apoptosis and intracellular calcium,and its mechanism in human lung adenocarcinoma cell line A549. Methods Human lung adenocarcinoma A549 cells were incubated in vitro and assigned with OA concentrations of 0,10,20 and 40μg/mL. The apoptosis status of A549 cell line was detected with Annexin V-FITC/PI by flow cytometry (FCM); fluorescence intensity (FI) of A549 cells was assessed and the level of intracellular calciu...

  2. Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

    Science.gov (United States)

    Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

    2016-07-01

    Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking.

  3. Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

    Science.gov (United States)

    Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

    2016-07-01

    Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. PMID:27262203

  4. Tevatron status

    International Nuclear Information System (INIS)

    The Fermilab Tevatron is both the world's highest energy accelerator system and first large-scale superconducting synchrotron. Since Tevatron commissioning in July 1983, the accelerator has operated in 1984, 1985 and 1987 with extracted beams of 800 GeV for three runs of fixed target physics, and in 1987, and 1988, with proton-antiproton colliding beams at 900 /times/ 900 GeV. This paper will focus on the collider operation of the Tevatron: its present status and the outlook for its longer-term future evolution. 18 refs., 3 figs., 2 tabs

  5. The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors

    Directory of Open Access Journals (Sweden)

    J.F. Cunha

    2001-03-01

    Full Text Available We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC50 values of 18 µM and Emax of 100% (N = 10 or 20 µM and Emax of 92% (N = 10, respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP. The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 ± 7.0, 43 ± 3.9 and 78 ± 5.6% in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively. Tetraethylammonium (100 µM, a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 µM, a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 ± 12%. Glibenclamide (1 or 3 µM, at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K+ channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 µM, a selective blocker of the large-conductance Ca2+-activated K+ channels, caused rightward shifts (6- and 7-fold of the gentisic acid concentration-relaxation curve. L-N G-nitroarginine (100 µM, a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 µM, while methylene blue (10 or 30 µM or ODQ (1 µM, the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-P-Cl-Phe6,Leu17[VIP] (0.1 µM, a VIP receptor antagonist

  6. Genetic variation in toll-like receptors and retinoic acid-inducible gene I and outcome of hepatitis C virus infection

    DEFF Research Database (Denmark)

    Clausen, L N; Ladelund, S; Weis, N;

    2014-01-01

    SNPs in the IkBε, rs2233437 and rs730775. Presence of one or two of the variant allele in rs2233437 had more than twofold higher odds of resolution in adjusted logistic regression (adjusted odds ratio (aOR), 2.6; (95% CI, 1.4, 4.8) P = 0.002). We identified polymorphisms in the IkBε gene associated......We evaluated the effects of genetic variation in toll-like receptors (TLR), retinoic acid-inducible gene I (RIG-I) and their signalling pathways on spontaneous hepatitis C virus (HCV) resolution. We screened 95 single-nucleotide polymorphisms (SNPs) in 22 genes. SNPs significantly associated...... with resolution in the discovery cohort were genotyped in a validation cohort. Multivariate logistic regression adjusted for sex, hepatitis B surface antigen, HIV infection and the interleukin-28B rs12979860 SNP was performed in the combined cohort. Haplotype reconstruction and linkage disequilibrium analysis...

  7. Gibberellic Acid-Induced Aleurone Layers Responding to Heat Shock or Tunicamycin Provide Insight into the N-Glycoproteome, Protein Secretion, and Endoplasmic Reticulum Stress

    DEFF Research Database (Denmark)

    Barba Espin, Gregorio; Dedvisitsakul, Plaipol; Hägglund, Per;

    2014-01-01

    The growing relevance of plants for the production of recombinant proteins makes understanding the secretory machinery, including the identification of glycosylation sites in secreted proteins, an important goal of plant proteomics. Barley (Hordeum vulgare) aleurone layers maintained in vitro...... respond to gibberellic acid by secreting an array of proteins and provide a unique system for the analysis of plant protein secretion. Perturbation of protein secretion in gibberellic acid-induced aleurone layers by two independent mechanisms, heat shock and tunicamycin treatment, demonstrated overlapping...... shock proteins, decreased in heat-shocked aleurone layers. Additionally, glycopeptide enrichment and N-glycosylation analysis identified 73 glycosylation sites in 65 aleurone layer proteins, with 53 of the glycoproteins found in extracellular fractions and 36 found in intracellular fractions...

  8. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice.

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Gupta

    Full Text Available Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse compared with anti-inflammatory drug diclofenac sodium (10 mg/kg] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histopathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model.

  9. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice

    Science.gov (United States)

    Gupta, Ashok Kumar; Parasar, Devraj; Sagar, Amin; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Renu; Ashish; Khatri, Neeraj

    2015-01-01

    Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histo-pathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model. PMID:26426535

  10. Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

    Science.gov (United States)

    Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

    2015-01-01

    Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration. PMID:26234512

  11. Tiagabine

    Science.gov (United States)

    ... a severe rash caused by taking a medication; status epilepticus (seizures following one another without a break); or ... taking tiagabine.you should know that seizures, including status epilepticus, have occurred in people without epilepsy who take ...

  12. Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression

    Directory of Open Access Journals (Sweden)

    Haybaeck J

    2015-02-01

    Full Text Available Johannes Haybaeck,1 Magdalena Postruznik,1 Christine L Miller,2 Jeannette R Dulay,3 Ida C Llenos,3,4 Serge Weis3,4 1Department of Neuropathology, Institute of Pathology, Medical University Graz, Graz, Austria; 2Department of Pediatrics, Johns Hopkins University, Baltimore, 3Laboratory of Brain Research and Neuropathology, Departments of Psychiatry and Pathology, Uniformed Services University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD, USA; 4Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria Background: Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1 is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients. Methods: In the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression. Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex. Results: All four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06 in schizophrenia and bipolar

  13. Prednisolone-appended alpha-cyclodextrin: alleviation of systemic adverse effect of prednisolone after intracolonic administration in 2,4,6-trinitrobenzenesulfonic acid-induced colitis rats.

    Science.gov (United States)

    Yano, H; Hirayama, F; Arima, H; Uekama, K

    2001-12-01

    The titled compound is a cyclodextrin derivative in which prednisolone 21-succinate (PDsuc) is covalently bound to one of the secondary hydroxyl groups of alpha-cyclodextrin (alpha-CyD) via an ester linkage. In this study, the PDsuc-appended alpha-CyD ester conjugate (PDsuc/alpha-CyD conjugate) was intracolonically administered to rats with 2,4,6-trinitrobenzensulfonic acid-induced colitis, and its antiinflammatory and systemic adverse effects were compared with those of prednisolone (PD) alone and the PD/2-hydroxypropyl-beta-CyD complex (PD/HP-beta-CyD complex), which is a noncovalent inclusion complex. Colonic damage score, ratio of distal colon wet weight to body weight, and myeloperoxidase activity were evaluated as measures of the therapeutic effect of PD, whereas the ratio of thymus wet weight to body weight was evaluated as a measure of the side effect of PD. The local antiinflammatory activity increased in the order of PD alone approximately PDsuc/alpha-CyD conjugate keeps the local concentration in the colon at a low but constant level. The results suggest that the PDsuc/alpha-CyD conjugate can alleviate the systemic adverse effect of PD while maintaining the therapeutic activity of PD. This kind of knowledge will be useful in the rational design of steroid prodrugs for the colon-specific drug delivery system. PMID:11745769

  14. Preconcentration and fluorimetric determination of polycyclic aromatic hydrocarbons based on the acid-induced cloud-point extraction with sodium dodecylsulfate

    Energy Technology Data Exchange (ETDEWEB)

    Goryacheva, Irina Yu.; Shtykov, Sergei N.; Loginov, Alexander S.; Panteleeva, Irina V. [Saratov State University, Chemistry Department, Saratov (Russian Federation)

    2005-07-01

    The acid-induced cloud-point extraction (CPE) technique based on sodium dodecylsulfate (SDS) micelles has been used for preconcentration of ten representatives of polycyclic aromatic hydrocarbons (PAHs) for the following fluorescence determination. The effect of the acidity of solution, SDS and electrolyte concentrations, centrifugation time and rate on the two-phase separation process and extraction percentages of PAHs have systematically been examined. Extraction percentages have been obtained for all PAHs after CPE ranged from 67 to 93%. Pyrene was used as a fluorescent probe to monitor the micropolarity of the surfactant-rich phase compared with SDS micelles and this allows one to conclude that water content in micellar phase after CPE is reduced. The spectral, metrological and analytical characteristics of PAH fluorimetric determination after acid-based CPE with sodium dodecylsulfate are presented. Advantages provided by using CPE in combination with fluorimetric determination of PAHs are discussed. The determination of benz[a]pyrene in tap water is presented as an example. (orig.)

  15. Receptor for advanced glycation end products plays a more important role in cellular survival than in neurite outgrowth during retinoic acid-induced differentiation of neuroblastoma cells.

    Science.gov (United States)

    Sajithlal, Gangadharan; Huttunen, Henri; Rauvala, Heikki; Munch, Gerald

    2002-03-01

    The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, is known to interact with amphoterin. This interaction has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, there is as yet no direct evidence of the relevance of this pathway to neurodifferentiation under physiological conditions. In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of RAGE by dominant negative and antisense strategies showed that RAGE is not required for process outgrowth or differentiation, although overexpression of RAGE accelerates the elongation of neuritic processes. Using the antisense strategy, amphoterin was shown to be essential for process outgrowth and differentiation, suggesting that amphoterin may interact with other molecules to exert its effect in this context. Interestingly, the survival of the neuroblastoma cells treated with retinoic acid was partly dependent on the expression of RAGE, and inhibition of RAGE function partially blocked the increase in anti-apoptotic protein Bcl-2 following retinoic acid treatment. Based on these results we propose that a combination therapy using RAGE blockers and retinoic acid may prove as a useful approach for chemotherapy for the treatment of neuroblastoma.

  16. Effect of dietary fibers on cholic acid induced cell proliferation in the colonic epithelium of C57BL/6J mice

    International Nuclear Information System (INIS)

    It has been postulated that high fat diets promote tumorigenesis by increasing the level of secondary bile acids in the colonic lumen. Dietary fibers are thought to be protective perhaps through their interaction with bile acids. In the present study, animals were fed diets containing either 0%, 5%, or 10% cellulose (C), pectin (P), or wheat bran (WB). The diets were formulated to contain either 0% (control) or 0.2% cholic acid (test). After two weeks of dietary treatment the animals were injected with [3H]-thymidine and their colons were processed for autoradiography. The number of labeled cells (LC) in the colonic crypts was determined. Among the control diets, 10%P induced a two-fold increase in the LC. All the test groups had significantly higher LC than in their controls. However, the C group excited a higher LC than the P or WB groups (5.2 +/- 0.8 vs 3.9 +/- 0.8 or 3.9 +/- 0.6). These results were substantiated by metaphase arrest technique. The authors results show that nonfermentable fiber does not alleviate bile acid induced cell proliferative activity in the colon whereas fermentable fibers will counteract the promotional effect of a high fat diet

  17. Alkali- or acid-induced changes in structure, moisture absorption ability and deacetylating reaction of β-chitin extracted from jumbo squid (Dosidicus gigas) pens.

    Science.gov (United States)

    Jung, Jooyeoun; Zhao, Yanyun

    2014-01-01

    Alkali- or acid-induced structural modifications in β-chitin from squid (Dosidicus gigas, d'Orbigny, 1835) pens and their moisture absorption ability (MAA) and deacetylating reaction were investigated and compared with α-chitin from shrimp shells. β-Chitin was converted into the α-form after 3h in 40% NaOH or 1-3 h in 40% HCl solution, and α-chitin obtained from NaOH treatment had higher MAA than had native α-chitin, due to polymorphic destructions. In contrast, induced α-chitin from acid treatment of β-chitin had few polymorphic modifications, showing no significant change (P>0.05) in MAA. β-Chitin was more susceptible to alkali deacetylation than was α-chitin, and required a lower concentration of NaOH and shorter reaction time. These results demonstrate that alkali- or acid-treated β-chitin retained high susceptibility toward solvents, which in turn resulted in good biological activity of β-chitosan for use as a natural antioxidant and antimicrobial substance or application as edible coatings and films for various food applications. PMID:24444948

  18. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    Science.gov (United States)

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways.

    Science.gov (United States)

    Ying, Tsung-Ho; Chen, Chia-Wei; Hsiao, Yu-Ping; Hung, Sung-Jen; Chung, Jing-Gung; Yang, Jen-Hung

    2013-10-01

    Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

  20. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    International Nuclear Information System (INIS)

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca2+ entrance was induced by A23187 in HepG2. Cell death, Ca2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca2+-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  1. Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I.

    Directory of Open Access Journals (Sweden)

    Seung Bum Park

    Full Text Available Hepatitis C virus (HCV actively evades host interferon (IFN responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP and poly(IC. The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity.

  2. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  3. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    Science.gov (United States)

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1295724

  4. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    Science.gov (United States)

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

  5. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    Science.gov (United States)

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2′-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  6. Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I

    Science.gov (United States)

    Park, Seung Bum; Seronello, Scott; Mayer, Wasima; Ojcius, David M.

    2016-01-01

    Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain) were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity. PMID:27404108

  7. Identification of a retinoic acid-inducible gene I from Japanese eel (Anguilla japonica) and expression analysis in vivo and in vitro.

    Science.gov (United States)

    Feng, Jianjun; Guo, Songlin; Lin, Peng; Wang, Yilei; Zhang, Ziping; Zhang, Zaipeng; Yu, Lili

    2016-08-01

    RIG-I (retinoic acid inducible gene-I) is one of the key cytosolic pattern recognition receptors (PRRs) for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). The full-length cDNA sequence of RIG-I (AjRIG-I) in Japanese eel (Anguilla japonica) was identified and characterized in this article. The full-length cDNA of AjRIG-I was 3468 bp, including a 5'-untranslated region (UTR) of 52 bp, a 3'-UTR of 617 bp and an open reading frame (ORF) of 2799 bp encoding a polypeptide of 933 amino acid residues with a calculated molecular mass of 106.2 kDa. NCBI CDD analysis showed that the AjRIG-I protein had the typical conserved domains, including two adjacent caspase activation and recruitment domains (CARDs), a DEXDc domain, a HELICc domain and a C-terminal regulatory domain (RD). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed a broad expression for AjRIG-I in a wide range of tissues, with the predominant expression in liver, followed by the gills, spleen, kidney, intestine, skin, and the very low expression in muscle and heart. The AjRIG-I expressions in liver, spleen and kidney were significantly induced following injection with LPS, the viral mimic poly I:C, and Aeromonas hydrophila infection. In vitro, the AjRIG-I transcripts of Japanese eel liver cells were significantly enhanced by poly I:C and PGN stimulation, down-regulated with CpG-DNA treatment whereas no change of the expression level was found post LPS challenge. These results collectively suggested AjRIG-I transcripts expression possibly play an important role in fish defense against viral and bacterial infection. PMID:27238428

  8. Stearoyl-CoA desaturase-1 (SCD1 augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Hiroki Matsui

    Full Text Available Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1 is a rate-limiting enzyme that converts saturated fatty acids (SFAs to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.

  9. Gibberellic acid-induced aleurone layers responding to heat shock or tunicamycin provide insight into the N-glycoproteome, protein secretion, and endoplasmic reticulum stress.

    Science.gov (United States)

    Barba-Espín, Gregorio; Dedvisitsakul, Plaipol; Hägglund, Per; Svensson, Birte; Finnie, Christine

    2014-02-01

    The growing relevance of plants for the production of recombinant proteins makes understanding the secretory machinery, including the identification of glycosylation sites in secreted proteins, an important goal of plant proteomics. Barley (Hordeum vulgare) aleurone layers maintained in vitro respond to gibberellic acid by secreting an array of proteins and provide a unique system for the analysis of plant protein secretion. Perturbation of protein secretion in gibberellic acid-induced aleurone layers by two independent mechanisms, heat shock and tunicamycin treatment, demonstrated overlapping effects on both the intracellular and secreted proteomes. Proteins in a total of 22 and 178 two-dimensional gel spots changing in intensity in extracellular and intracellular fractions, respectively, were identified by mass spectrometry. Among these are proteins with key roles in protein processing and secretion, such as calreticulin, protein disulfide isomerase, proteasome subunits, and isopentenyl diphosphate isomerase. Sixteen heat shock proteins in 29 spots showed diverse responses to the treatments, with only a minority increasing in response to heat shock. The majority, all of which were small heat shock proteins, decreased in heat-shocked aleurone layers. Additionally, glycopeptide enrichment and N-glycosylation analysis identified 73 glycosylation sites in 65 aleurone layer proteins, with 53 of the glycoproteins found in extracellular fractions and 36 found in intracellular fractions. This represents major progress in characterization of the barley N-glycoproteome, since only four of these sites were previously described. Overall, these findings considerably advance knowledge of the plant protein secretion system in general and emphasize the versatility of the aleurone layer as a model system for studying plant protein secretion.

  10. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    Science.gov (United States)

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  11. USCIS My Case Status

    Data.gov (United States)

    Department of Homeland Security — USCIS provide a way for the public who applied for U.S. citizenship to check the status of their application online. To view the status of a case, the application...

  12. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Directory of Open Access Journals (Sweden)

    Klingelhoeffer Christoph

    2012-05-01

    against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.

  13. The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism

    Directory of Open Access Journals (Sweden)

    Cascante Marta

    2011-04-01

    Full Text Available Abstract Background Maslinic acid, a pentacyclic triterpene found in the protective wax-like coating of the leaves and fruit of Olea europaea L., is a promising agent for the prevention of colon cancer. We have shown elsewhere that maslinic acid inhibits cell proliferation to a significant extent and activates mitochondrial apoptosis in colon cancer cells. In our latest work we have investigated further this compound's apoptotic molecular mechanism. Methods We used HT29 adenocarcinoma cells. Changes genotoxicity were analyzed by single-cell gel electrophoresis (comet assay. The cell cycle was determined by flow cytometry. Finally, changes in protein expression were examined by western blotting. Student's t-test was used for statistical comparison. Results HT29 cells treated with maslinic acid showed significant increases in genotoxicity and cell-cycle arrest during the G0/G1 phase after 72 hours' treatment and an apoptotic sub-G0/G1 peak after 96 hours. Nevertheless, the molecular mechanism for this cytotoxic effect of maslinic acid has never been properly explored. We show here that the anti-tumoral activity of maslinic acid might proceed via p53-mediated apoptosis by acting upon the main signaling components that lead to an increase in p53 activity and the induction of the rest of the factors that participate in the apoptotic pathway. We found that in HT29 cells maslinic acid activated the expression of c-Jun NH2-terminal kinase (JNK, thus inducing p53. Treatment of tumor cells with maslinic acid also resulted in an increase in the expression of Bid and Bax, repression of Bcl-2, release of cytochrome-c and an increase in the expression of caspases -9, -3, and -7. Moreover, maslinic acid produced belated caspase-8 activity, thus amplifying the initial mitochondrial apoptotic signaling. Conclusion All these results suggest that maslinic acid induces apoptosis in human HT29 colon-cancer cells through the JNK-Bid-mediated mitochondrial apoptotic

  14. Heuristic status polling

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Heidelberger, Philip; Kumar, Sameer; Parker, Jeffrey J.; Ratterman, Joseph D.

    2011-06-07

    Methods, compute nodes, and computer program products are provided for heuristic status polling of a component in a computing system. Embodiments include receiving, by a polling module from a requesting application, a status request requesting status of a component; determining, by the polling module, whether an activity history for the component satisfies heuristic polling criteria; polling, by the polling module, the component for status if the activity history for the component satisfies the heuristic polling criteria; and not polling, by the polling module, the component for status if the activity history for the component does not satisfy the heuristic criteria.

  15. Service Level Status

    CERN Multimedia

    Lopienski, S

    2007-01-01

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them.

  16. Status and the brain.

    OpenAIRE

    Utevsky, Amanda V.; Platt, Michael L.

    2014-01-01

    Social hierarchy is a fact of life for many animals. Navigating social hierarchy requires understanding one's own status relative to others and behaving accordingly, while achieving higher status may call upon cunning and strategic thinking. The neural mechanisms mediating social status have become increasingly well understood in invertebrates and model organisms like fish and mice but until recently have remained more opaque in humans and other primates. In a new study in this issue, Noonan ...

  17. SIS - Status Determination

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Status Determination dataset within the Species Information System (SIS) contains information related to overfishing, overfished, and approaching overfished...

  18. Status of APEmille

    CERN Document Server

    Bartoloni, A; Cabibbo, Nicola; Calvayrac, F; Della Morte, M; De Pietri, R; De Riso, P; Carlo, F D; Renzo, F D; Errico, W; Frezzotti, R; Giorgino, T; Heitger, J; Lonardo, A; Loukianov, M; Magazzù, G; Micheli, J; Morénas, V; Paschedag, N; Pène, O; Petronzio, Roberto; Pleiter, D; Rapuano, F; Rolf, J; Rossetti, D; Sartori, L; Simma, H; Schifano, F; Torelli, M; Tripiccione, R; Vicini, P; Wegner, P

    2002-01-01

    This paper presents the status of the APEmille project, which is essentially completed, as far as machine development and construction is concerned. Several large installations of APEmille are in use for physics production runs leading to many new results presented at this conference. This paper briefly summarizes the APEmille architecture, reviews the status of the installations and presents some performance figures for physics codes.

  19. Domain-confined catalytic soot combustion over Co3O4 anchored on a TiO2 nanotube array catalyst prepared by mercaptoacetic acid induced surface-grafting

    Science.gov (United States)

    Ren, Jiale; Yu, Yifu; Dai, Fangfang; Meng, Ming; Zhang, Jing; Zheng, Lirong; Hu, Tiandou

    2013-11-01

    Herein, we introduce a specially designed domain-confined macroporous catalyst, namely, the Co3O4 nanocrystals anchored on a TiO2 nanotube array catalyst, which was synthesized by using the mercaptoacetic acid induced surface-grafting method. This catalyst exhibits much better performance for catalytic soot combustion than the conventional TiO2 powder supported one in gravitational contact mode (GMC).Herein, we introduce a specially designed domain-confined macroporous catalyst, namely, the Co3O4 nanocrystals anchored on a TiO2 nanotube array catalyst, which was synthesized by using the mercaptoacetic acid induced surface-grafting method. This catalyst exhibits much better performance for catalytic soot combustion than the conventional TiO2 powder supported one in gravitational contact mode (GMC). Electronic supplementary information (ESI) available: The images of XRD, UV-vis, EDX and soot-TPR. The table providing information on Co/Ti-NA catalysts. See DOI: 10.1039/c3nr03757f

  20. Neu1 sialidase and matrix metalloproteinase-9 cross-talk regulates nucleic acid-induced endosomal TOLL-like receptor-7 and -9 activation, cellular signaling and pro-inflammatory responses.

    Science.gov (United States)

    Abdulkhalek, Samar; Szewczuk, Myron R

    2013-11-01

    The precise mechanism(s) by which intracellular TOLL-like receptors (TLRs) become activated by their ligands remains unclear. Here, we report a molecular organizational G-protein coupled receptor (GPCR) signaling platform to potentiate a novel mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B GPCR, all of which form a tripartite complex with TLR-7 and -9. siRNA silencing Neu1, MMP-9 and neuromedin-B GPCR in RAW-blue macrophage cells significantly reduced TLR7 imiquimod- and TLR9 ODN1826-induced NF-κB (NF-κB-pSer(536)) activity. Tamiflu, specific MMP-9 inhibitor, neuromedin B receptor specific antagonist BIM23127, and the selective inhibitor of whole heterotrimeric G-protein complex BIM-46174 significantly block nucleic acid-induced TLR-7 and -9 MyD88 recruitment, NF-κB activation and proinflammatory TNFα and MCP-1 cytokine responses. For the first time, Neu1 clearly plays a central role in mediating nucleic acid-induced intracellular TLR activation, and the interactions involving NMBR-MMP9-Neu1 cross-talk constitute a novel intracellular TLR signaling platform that is essential for NF-κB activation and pro-inflammatory responses. PMID:23827939