Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers.

Abstract:

OBJECTIVE:Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease. METHODS:As development of novel radiotracers and on-site setup of existing radiotracers is highly time-consuming and expensive, we used dual-centre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18 F-flumazenil (18 F-FMZ; GABAA receptor), 18 F-FPEB (metabotropic glutamate receptor 5; mGluR5), 18 F-flutriciclamide (translocator protein; TSPO, microglia activation) and 18 F-deprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpine-induced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12-14 weeks after SE) were normalized to a calibration curve, co-registered to an MRI-based 2D region-of-interest atlas, and activity concentration (Bq/mm2 ) was calculated. RESULTS:In epileptogenesis-associated brain regions, 18 F-FMZ and 18 F-FPEB showed an early decrease after SE. 18 F-FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18 F-FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18 F-flutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5-15 days and decreasing during the chronic phase. On the other hand, 18 F-deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase. SIGNIFICANCE:Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter-related targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Bascuñana P,Gendron T,Sander K,Jahreis I,Polyak A,Ross TL,Bankstahl M,Arstad E,Bankstahl JP

doi

10.1111/epi.16353

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

2325-2333

issue

11

eissn

0013-9580

issn

1528-1167

journal_volume

60

pub_type

杂志文章
  • Epilepsy, antiepileptic drugs, and the risk of spontaneous abortion.

    abstract::The possible effect of in utero antiepileptic drug (AED) exposure on the incidence of spontaneous abortion was evaluated among pregnancies of women with epilepsy and the wives of men with epilepsy. The proportion of pregnancy outcomes terminating in spontaneous abortion, the gestational age-specific rates of spontaneo...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1988.tb03745.x

    authors: Annegers JF,Baumgartner KB,Hauser WA,Kurland LT

    更新日期:1988-07-01 00:00:00

  • Complex effects of eslicarbazepine on inhibitory micro networks in chronic experimental epilepsy.

    abstract:OBJECTIVE:Many antiseizure drugs (ASDs) act on voltage-dependent sodium channels, and the molecular basis of these effects is well established. In contrast, how ASDs act on the level of neuronal networks is much less understood. METHODS:In the present study, we determined the effects of eslicarbazepine (S-Lic) on diff...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.16808

    authors: Schmidt S,Pothmann L,Müller-Komorowska D,Opitz T,Soares da Silva P,Beck H

    更新日期:2021-01-16 00:00:00

  • A kindling-like effect induced by repeated exposure to heated water in rats.

    abstract::Hyperthermia was induced in mature rats by immersing them in 20 cm of 45 degrees C water for 4 min. Rats were made hyperthermic once every 4 days for six exposures. A significant number had at least one convulsion by the third exposure. During the seventh exposure, 2 weeks after the sixth exposure, twice as many rats ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1984.tb04192.x

    authors: Klauenberg BJ,Sparber SB

    更新日期:1984-06-01 00:00:00

  • Single and multiple clusters of magnetoencephalographic dipoles in neocortical epilepsy: significance in characterizing the epileptogenic zone.

    abstract:PURPOSE:To characterize the epileptogenic zone in neocortical epilepsy (NE) by using magnetoencephalography (MEG). METHODS:We defined and compared locations of single and multiple clusters of equivalent current dipoles (ECDs) for interictal spikes with MRI findings, ictal-onset zones (IOZs) from subdural electroenceph...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2006.00428.x

    authors: Oishi M,Kameyama S,Masuda H,Tohyama J,Kanazawa O,Sasagawa M,Otsubo H

    更新日期:2006-02-01 00:00:00

  • Surgical treatment of a case of early infantile epileptic encephalopathy with suppression-bursts associated with focal cortical dysplasia.

    abstract::We report a surgically treated case of early infantile epileptic encephalopathy (EIEE) with suppression-bursts associated with focal cortical dysplasia. Tonic-clonic seizures followed by a series of spasms occurred about a hundred times a day at a few days of age. Interictal electroencephalogram (EEG) revealed a suppr...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1999.tb00719.x

    authors: Komaki H,Sugai K,Sasaki M,Hashimoto T,Arai N,Takada E,Maehara T,Shimizu H

    更新日期:1999-03-01 00:00:00

  • Effects of monotherapy and polytherapy on the blink reflex in epileptic patients.

    abstract::We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant dif...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1993.tb02137.x

    authors: Lancman ME,Cristiano E,Golimstok A,Granillo RJ

    更新日期:1993-11-01 00:00:00

  • Prognosis of epilepsy in newly referred patients: a multicenter prospective study. Collaborative Group for the Study of Epilepsy.

    abstract::A multicenter prospective study was initiated at the time of first antiepileptic treatment for afebrile seizures with 283 unselected patients in Italy. Each patient started with monotherapy at standard daily doses. Data were collected at admission, at scheduled 6-month exams, and at unscheduled exams and included age,...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1988.tb03712.x

    authors: Beghi E,Tognoni G

    更新日期:1988-05-01 00:00:00

  • Seizures induce obstructive apnea in DBA/2J audiogenic seizure-prone mice: Lifesaving impact of tracheal implants.

    abstract::The mechanism(s) for sudden death in epilepsy (SUDEP) remain(s) unknown, but seizure spread to brainstem areas serving autonomic and respiratory function is critical. In a rat model, we established a mechanism for SUDEP that involves seizure-induced laryngospasm and obstructive apnea lasting until respiratory arrest. ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.16431

    authors: Irizarry R,Sukato D,Kollmar R,Schild S,Silverman J,Sundaram K,Stephenson S,Stewart M

    更新日期:2020-02-01 00:00:00

  • Antiepileptic drug mechanisms of action.

    abstract::Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium channels, gamma-aminobutyric acid type A (GABAA) receptors, or calcium channels. Benzodiazepines and barbiturates enhance GABAA recept...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1157.1995.tb05996.x

    authors: Macdonald RL,Kelly KM

    更新日期:1995-01-01 00:00:00

  • Clinically unsuspected cerebral infarction revealed by computed tomography scanning in late onset epilepsy.

    abstract::The computed tomography (CT) scans of 132 patients with late onset epilepsy were compared with the CT scans of an age- and sex-matched control group. Patients with neurologic symptoms in addition to epilepsy, patients with a definite antecedent cause for epilepsy, and patients with tumours on CT scanning were excluded...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1988.tb04418.x

    authors: Roberts RC,Shorvon SD,Cox TC,Gilliatt RW

    更新日期:1988-03-01 00:00:00

  • Better object recognition and naming outcome with MRI-guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy.

    abstract:OBJECTIVES:Patients with temporal lobe epilepsy (TLE) experience significant deficits in category-related object recognition and naming following standard surgical approaches. These deficits may result from a decoupling of core processing modules (e.g., language, visual processing, and semantic memory), due to "collate...

    journal_title:Epilepsia

    pub_type: 临床试验,杂志文章

    doi:10.1111/epi.12860

    authors: Drane DL,Loring DW,Voets NL,Price M,Ojemann JG,Willie JT,Saindane AM,Phatak V,Ivanisevic M,Millis S,Helmers SL,Miller JW,Meador KJ,Gross RE

    更新日期:2015-01-01 00:00:00

  • Lack of alpha 1b-adrenergic receptor protects against epileptic seizures.

    abstract:PURPOSE:The role of alpha 1b-adrenergic receptor (alpha 1b-AR) in relation with neuronal degeneration, drug addiction, and seizure susceptibility has recently emerged. In particular, mice that overexpress alpha 1b-AR undergo spontaneous epileptic seizures and progressive neuronal loss in a variety of brain areas. There...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2008.01972.x

    authors: Pizzanelli C,Lazzeri G,Fulceri F,Giorgi FS,Pasquali L,Cifelli G,Murri L,Fornai F

    更新日期:2009-01-01 00:00:00

  • Reevaluation of surgical failures and the role of reoperation in 39 patients with frontal lobe epilepsy.

    abstract::Between 1929 and 1980, 284 patients with refractory nontumoral frontal lobe epilepsy (FLE) underwent operation at the Montreal Neurological Institute (MNI). We studied 39 patients (14%) who required reoperation. Mean age at the time of first operation was 18 years and at reoperation was 22 years. Clinical manifestatio...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1994.tb02914.x

    authors: Salanova V,Quesney LF,Rasmussen T,Andermann F,Olivier A

    更新日期:1994-01-01 00:00:00

  • ILAE official report: a practical clinical definition of epilepsy.

    abstract::Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a t...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/epi.12550

    authors: Fisher RS,Acevedo C,Arzimanoglou A,Bogacz A,Cross JH,Elger CE,Engel J Jr,Forsgren L,French JA,Glynn M,Hesdorffer DC,Lee BI,Mathern GW,Moshé SL,Perucca E,Scheffer IE,Tomson T,Watanabe M,Wiebe S

    更新日期:2014-04-01 00:00:00

  • Antiepileptic drugs and vitamin D supplementation.

    abstract::The incidence of biochemical signs of vitamin D deficiency and the effects of vitamin D supplementation were investigated in 83 children and 95 adults on chronic antiepileptic therapy and 40 mentally retarded controls living under comparable conditions. Low 25-hydroxyvitamin D and serum calcium, and elevated immunorea...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1979.tb04771.x

    authors: Offermann G,Pinto V,Kruse R

    更新日期:1979-02-01 00:00:00

  • Clobazam for treatment of intractable epilepsy: a critical assessment.

    abstract::Clobazam (CLB), a 1,5-benzodiazepine, is a remarkably effective add-on drug for individual patients with refractory partial epilepsy. CLB has an excellent safety record. As with all benzodiazepines used for treating epilepsy, sedation and withdrawal effects, together with the development of tolerance, limit its useful...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1157.1994.tb05979.x

    authors: Schmidt D

    更新日期:1994-01-01 00:00:00

  • Distinction between normal and epileptic rhythms in rodent sensorimotor cortex.

    abstract::Characteristics of spontaneous spindling in electrocorticograms from awake rodents are described. Comparisons are made between this spontaneous activity and epileptic activity generated in the sensorimotor cortex. ...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1979.tb04833.x

    authors: Hammond EJ,Villarreal HJ,Wilder BJ

    更新日期:1979-10-01 00:00:00

  • Seizure-associated aphasia has good lateralizing but poor localizing significance.

    abstract:OBJECTIVE:To investigate the occurrence of ictal and postictal aphasia in different focal epilepsy syndromes. METHODS:We retrospectively analyzed the video-electroencephalographic monitoring data of 1,118 patients with focal epilepsy for seizure-associated aphasia (SAA). Statistical analysis included chi-square analys...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13835

    authors: Loesch AM,Steger H,Losher C,Hartl E,Rémi J,Vollmar C,Noachtar S

    更新日期:2017-09-01 00:00:00

  • Symptomatic occipital lobe epilepsy.

    abstract::Symptomatic occipital lobe epilepsy is increasingly recognized among patients with partial-onset seizures. Although traditional clinical and electroencephalographic criteria had defined occipital lobe epilepsy in the past, new neuroimaging techniques and the recognition of specific syndromes associated with occipital ...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1157.1998.tb05122.x

    authors: Kuzniecky R

    更新日期:1998-01-01 00:00:00

  • Lingual seizures.

    abstract::A 73-year-old patient with hyperglycemia and rheumatoid arthritis presented with attacks of involuntary lingual movements that were associated with pain at the base of the tongue, often followed by aversion of head and eyes to the left with clonic contractions of the left corner of the mouth. Seizures could be induced...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1988.tb05094.x

    authors: Neufeld MY,Blumen SC,Nisipeanu P,Korczyn AD

    更新日期:1988-01-01 00:00:00

  • The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population.

    abstract::The use of lamotrigine (LTG) can be limited by the occurrence of cutaneous adverse drug reactions (cADRs) that range from maculopapular eruption (MPE) to the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis. A few human leukocyte antigen (HLA)-related genetic risk factors for carbamazepine-induced c...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.13087

    authors: Moon J,Park HK,Chu K,Sunwoo JS,Byun JI,Lim JA,Kim TJ,Shin JW,Lee ST,Jung KH,Jung KY,Jeon D,Kim DW,Yu KS,Jang IJ,Kang HR,Park HW,Lee SK

    更新日期:2015-10-01 00:00:00

  • Systematic testing of medical intractability for carbamazepine, phenytoin, and phenobarbital or primidone in monotherapy for patients considered for epilepsy surgery.

    abstract:PURPOSE:To assess medical intractability in patients considered for restrictive epilepsy surgery. METHODS:Seventy-four patients received single drug treatment with carbamazepine (CBZ), phenytoin (PHT), and either phenobarbital (PB) or primidone (PRM). Medical intractability was established if seizure control was not o...

    journal_title:Epilepsia

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1528-1157.1996.tb00632.x

    authors: Hermanns G,Noachtar S,Tuxhorn I,Holthausen H,Ebner A,Wolf P

    更新日期:1996-07-01 00:00:00

  • Clinical pharmacology of lamotrigine.

    abstract::The pharmacokinetics and pharmacodynamics of lamotrigine (LTG), a new antiepileptic drug (AED), were studied in healthy volunteers. In an open dose-escalating study, LTG 240 mg produced peak plasma concentrations of around 3 micrograms/mg with no significant adverse events. Subsequent pharmacokinetic studies revealed ...

    journal_title:Epilepsia

    pub_type: 临床试验,杂志文章,评审

    doi:10.1111/j.1528-1157.1991.tb05883.x

    authors: Peck AW

    更新日期:1991-01-01 00:00:00

  • Medical management of refractory epilepsy--practical treatment with novel antiepileptic drugs.

    abstract::The ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of dif...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/epi.12494

    authors: Ben-Menachem E

    更新日期:2014-01-01 00:00:00

  • Estrogen treatment protects GABA(B) inhibition in the dentate gyrus of female rats after kainic acid-induced status epilepticus.

    abstract:PURPOSE:We used the paired-pulse inhibition paradigm to determine whether the cell loss in the hilus of the dentate gyrus of female rats after kainic acid (KA)-induced status epilepticus (SE) is associated with functional changes in the dentate gyrus. Additionally, we determined whether the lost function could be prese...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1046/j.1528-1157.43.s.5.3.x

    authors: Velísek L,Velísková J

    更新日期:2002-01-01 00:00:00

  • Successful treatment for refractory convulsive status epilepticus by non-parenteral lacosamide.

    abstract::Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory C...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2009.02256.x

    authors: Tilz C,Resch R,Hofer T,Eggers C

    更新日期:2010-02-01 00:00:00

  • Hippocampal T2 signal change during amygdala kindling epileptogenesis.

    abstract:PURPOSE:The rat electrical amygdala kindling model is one of the most widely studied animal models of temporal lobe epilepsy (TLE); however, the processes underlying epileptogenesis in this model remain incompletely understood. Magnetic resonance imaging (MRI) is a powerful method to investigate epileptogenesis, allowi...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2006.00368.x

    authors: Jupp B,Williams JP,Tesiram YA,Vosmansky M,O'Brien TJ

    更新日期:2006-01-01 00:00:00

  • Cognitive dysfunction associated with antiepileptic drug therapy.

    abstract::Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of thes...

    journal_title:Epilepsia

    pub_type: 杂志文章,评审

    doi:10.1111/j.1528-1157.1987.tb05767.x

    authors: Vining EP

    更新日期:1987-01-01 00:00:00

  • Febrile seizures: clinical characteristics and initial EEG.

    abstract::We examined the relationship between clinical characteristics and EEG classification in all children with febrile seizures examined at the University Pediatric Clinic, Skopje, Yugoslavia between 1982 and 1984. This is the only facility in Macedonia providing EEG or neurologic consultation for children. EEGs were class...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1157.1992.tb02282.x

    authors: Sofijanov N,Emoto S,Kuturec M,Dukovski M,Duma F,Ellenberg JH,Hirtz DG,Nelson KB

    更新日期:1992-01-01 00:00:00

  • Interobserver reliability of video recording in the diagnosis of nocturnal frontal lobe seizures.

    abstract:BACKGROUND:Nocturnal frontal lobe seizures (NFLS) show one or all of the following semeiological patterns: (1) paroxysmal arousals (PA: brief and sudden recurrent motor paroxysmal behavior); (2) hyperkinetic seizures (HS: motor attacks with complex dyskinetic features); (3) asymmetric bilateral tonic seizures (ATS: mot...

    journal_title:Epilepsia

    pub_type: 杂志文章

    doi:10.1111/j.1528-1167.2007.01121.x

    authors: Vignatelli L,Bisulli F,Provini F,Naldi I,Pittau F,Zaniboni A,Montagna P,Tinuper P

    更新日期:2007-08-01 00:00:00