Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 13.150
Filtrar
1.
Am J Case Rep ; 22: e931360, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33866321

RESUMO

BACKGROUND The electroencephalographic (EEG) findings associated with tetrahydrocannabinol (THC) use, particularly in concentrated form, are not well-described, despite the current widespread availability of these products. There is a lack of prior research describing the EEG findings in adolescent cannabis users, and the effects of THC on the seizure threshold have been variably reported. CASE REPORT A 17-year-old girl with no prior history of seizures or known seizure risk factors presented to an Emergency Department with acutely abnormal behavior in the setting of daily vaping of highly concentrated THC marijuana ("wax"). On admission, she had a witnessed generalized tonic-clonic seizure. Urine toxicology was positive for THC, and an extensive evaluation for other etiologies of her encephalopathy was unrevealing. Extended EEG on admission showed mild diffuse background slowing with occasional bifronto-centrally predominant sharp and spike wave discharges. Seven days later, without interim antiseizure medications, a repeat extended EEG showed resolution of the previously seen interictal findings. CONCLUSIONS The clinical and EEG findings were temporally associated with the patient's use of concentrated THC and may represent a constellation of symptoms of a THC wax toxidrome. In this case, THC was associated with lowering the seizure threshold and triggering a provoked seizure in an adolescent with no prior evidence of seizure tendency. This case also suggests the possibility of THC concentrate itself generating epileptiform discharges, as has previously been described with synthetic cannabinoid use.


Assuntos
Canabinoides/efeitos adversos , Dronabinol/efeitos adversos , Eletroencefalografia/efeitos dos fármacos , Convulsões/diagnóstico por imagem , Adolescente , Canabinoides/administração & dosagem , Dronabinol/administração & dosagem , Feminino , Humanos , Masculino , Convulsões/induzido quimicamente
2.
Nat Commun ; 12(1): 2206, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850125

RESUMO

Spreading depression (SD) is an intense and prolonged depolarization in the central nervous systems from insect to man. It is implicated in neurological disorders such as migraine and brain injury. Here, using an in vivo mouse model of focal neocortical seizures, we show that SD may be a fundamental defense against seizures. Seizures induced by topical 4-aminopyridine, penicillin or bicuculline, or systemic kainic acid, culminated in SDs at a variable rate. Greater seizure power and area of recruitment predicted SD. Once triggered, SD immediately suppressed the seizure. Optogenetic or KCl-induced SDs had similar antiseizure effect sustained for more than 30 min. Conversely, pharmacologically inhibiting SD occurrence during a focal seizure facilitated seizure generalization. Altogether, our data indicate that seizures trigger SD, which then terminates the seizure and prevents its generalization.


Assuntos
Depressão , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , 4-Aminopiridina , Animais , Bicuculina/farmacologia , Tronco Encefálico , Depressão Alastrante da Atividade Elétrica Cortical , Feminino , Técnicas de Introdução de Genes , Ácido Caínico/farmacologia , Masculino , Camundongos , Sistema Nervoso , Optogenética , Penicilinas/farmacologia , Bloqueadores dos Canais de Potássio/efeitos adversos , Convulsões/patologia , Tetrodotoxina/farmacologia
3.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672922

RESUMO

The identification of improved medical countermeasures against exposure to chemical warfare nerve agents (CWNAs), a class of organophosphorus compounds, is dependent on the choice of animal model used in preclinical studies. CWNAs bind to acetylcholinesterase and prevent the catalysis of acetylcholine, causing a plethora of peripheral and central physiologic manifestations, including seizure. Rodents are widely used to elucidate the effects of CWNA-induced seizure, albeit with a caveat: they express carboxylesterase activity in plasma. Carboxylesterase, an enzyme involved in the detoxification of some organophosphorus compounds, plays a scavenging role and decreases CWNA availability, thus exerting a protective effect. Furthermore, species-specific amino acid differences in acetylcholinesterase confound studies that use oximes or other compounds to restore its function after inhibition by CWNA. The creation of a human acetylcholinesterase knock-in/serum carboxylesterase knockout (C57BL/6-Ces1ctm1.1LocAChEtm1.1Loc/J; a.k.a KIKO) mouse may facilitate better modeling of CWNA toxicity in a small rodent species. The current studies characterize the effects of exposure to soman, a highly toxic CWNA, and evaluate the efficacy of anti-seizure drugs in this newly developed KIKO mouse model. Data demonstrate that a combination of midazolam and ketamine reduces seizure duration and severity, eliminates the development of spontaneous recurrent seizures, and protects certain brain regions from neuronal damage in a genetically modified model with human relevance to organophosphorus compound toxicity. This new animal model and the results of this study and future studies using it will enhance medical countermeasures development for both defense and homeland security purposes.


Assuntos
Acetilcolinesterase/metabolismo , Carboxilesterase/metabolismo , Modelos Animais de Doenças , Contramedidas Médicas , Soman/toxicidade , Acetilcolinesterase/genética , Anestésicos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Carboxilesterase/genética , Substâncias para a Guerra Química/toxicidade , Humanos , Ketamina/farmacologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Midazolam/farmacologia , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Convulsões/prevenção & controle
4.
Chem Biol Interact ; 340: 109447, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33771525

RESUMO

Accumulating evidences indicate that thiamine plays a vital role in the nervous system. However, questions exist as to how it causes epilepsy, neuronal damage, and antiepileptic mechanisms. The study looked at how the thiamine supplement impacted pentylenetetrazole (PTZ)-induced seizures in rats and pentylenetetrazole-induced neurotoxicity in the SH-SY5Y cell line. We used twenty-four male rats and they were randomly divided into 4 groups as control, saline (1 mL/kg/day serum physiologic) + PTZ, thiamine (50 mg/kg/day) + PTZ, and thiamine (50 mg/kg/day) for 10 days. PTZ (45 mg/kg) was given to activate the seizure on day 10. Memory efficiency was measured by using passive avoidance. The brain levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) were analyzed by using ELISA kits. SH-SY5Y cells were treated with/without thiamine for 1 h, followed by PTZ (30 µm) at a medium level to trigger neurotoxicity. Cell viability, total antioxidant status, total oxidant status, and apoptosis were assayed in the SH-SY5Y cells. Thiamine delayed the initiation of epileptic seizures and increased memory damage. In addition, 8-OHdG, caspase-3, NO, and cGMP levels were significantly reduced in the brain and prevented pentylenetetrazole-induced neurotoxicity, apoptosis, enhanced antioxidant, and reduced oxidant in SH-SY5Y cells. Thiamine dramatically altered seizures, memory loss, oxidative stress, and apoptosis. Thiamine has a preventative effect on PTZ-induced seizures in rats and PTZ-induced neurotoxicity in SH-SY5Y neuroblastoma cells. It could prevent oxidative stress and signaling of NO/cGMP. Thiamine supplement could be used as an additional therapeutic agent in epilepsy.


Assuntos
Apoptose/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Convulsões/tratamento farmacológico , Tiamina/farmacologia , Animais , Anticonvulsivantes/farmacologia , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Masculino , Memória/efeitos dos fármacos , Neurônios/metabolismo , Pentilenotetrazol/farmacologia , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/metabolismo
5.
Epilepsy Behav ; 117: 107881, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33711684

RESUMO

In the treatment of anxiety and seizures, drugs of the benzodiazepine (BZD) class are used, which act on the Central Nervous System (CNS) through the neurotransmitter gamma-aminobutyric acid (GABA). Flavonoids modulate GABAA receptors. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of synthetic chalcones and their mechanisms of action via the GABAergic system, using adult zebrafish (ZFa). The animals were treated with chalcones (4.0 or 20 or 40 mg/kg; 20 µL; i.p) and submitted to the open field and 96 h toxicity test. Chalcones that cause locomotor alteration were evaluated in the light and dark anxiolytic test. The same doses of chalcones were evaluated in the anticonvulsant test. The lowest effective dose was chosen to assess the possible involvement in the GABAA receptor by blocking the flumazenil (fmz) antagonist. No chalcone was toxic and altered ZFa's locomotion. All chalcones had anxiolytic and anticonvulsant effects, mainly chalcones 1, where all doses showed effects in both tests. These effects were blocked by Fmz (antagonist GABAA), where it shows evidence of the performance of these activities of the GABA system. Therefore, this study demonstrated in relation to structure-activity, that the position of the substituents is important in the intensity of activities and that the absence of toxicity and the action of these compounds in the CNS, shows the pharmacological potential of these molecules, and, therefore, the insights are designed for the development of new drugs.


Assuntos
Ansiolíticos , Chalconas , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Comportamento Animal , Chalconas/uso terapêutico , Receptores de GABA-A , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Peixe-Zebra
7.
Epilepsy Behav ; 116: 107797, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33561766

RESUMO

AIM: Depression is the major psychiatric disorder in patients with epilepsy. Vortioxetine is a novel antidepressant drug for the treatment of major depressive disorders. In the present study, effects of vortioxetine were evaluated in different experimental epilepsy models of rats. MATERIALS AND METHODS: Fifty-six adult male Wistar rats and 28 WAG/Rij rats were divided into 12 groups of 7 rats each. Experiments were conducted with penicillin (500 IU, i.c.) and pentylenetetrazole models (50 mg/kg, intraperitoneally (i.p.)) in Wistar rats and genetic absence epileptic WAG/Rij rats. The vortioxetine (1, 5, or 10 mg/kg, i.p.) was evaluated in these three models. All groups were compared with their control groups. RESULTS: In the penicillin-induced seizure model, 1, 5, or 10 mg/kg vortioxetine administration significantly decreased mean spike frequency. In the pentylenetetrazole-induced seizure model, 1, 5, or 10 mg/kg vortioxetine demonstrated a significant dose-dependent decrease in mean spike frequency, an increase in the latency to minor and major seizures, and a decrease in total duration of major seizure and convulsion stage. In genetic absence epileptic WAG/Rij rats, 1 mg/kg vortioxetine caused no significant alteration in the number and duration of SWDs compared to the controls, while 5 and 10 mg/kg doses of vortioxetine increased the number and duration of SWDs. Amplitude of the epileptiform activity did not change in any of the experimental epilepsy models. CONCLUSION: The results of this study suggested that vortioxetine has anticonvulsant activity in penicillin- and pentylenetetrazole-induced seizure models. However, it exhibited proconvulsant activity in the absence epileptic WAG/Rij rats.


Assuntos
Transtorno Depressivo Maior , Epilepsia Tipo Ausência , Animais , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia Tipo Ausência/induzido quimicamente , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/genética , Humanos , Masculino , Penicilinas/toxicidade , Pentilenotetrazol/toxicidade , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Vortioxetina
8.
Arch Oral Biol ; 125: 105076, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33636410

RESUMO

OBJECTIVE: The aim of this study was to investigate the effects of pre-pregnancy chronic exposure to Porphyromonas gingivalis LPS (Pg LPS) on the learning, memory, and seizure susceptibility of the offspring. DESIGN: To achieve periodontitis, Pg LPS (5 µg/kg) was injected into the gingival of five female rats every 48 h for three weeks. Five control female rats received saline (0.9 %) and five female were kept intact. The concentrations of TNF-α and IL-6 were measured in the blood samples. One week after the final injection, females were mated with intact males. Following birth and weaning, two male and two female offspring were randomly selected from each mother, and new groups of male and female offspring were defined for behavioral assessments. Morris water maze was used to evaluate spatial memory, shuttle box was used to investigate avoidance memory and a pentylenetetrazole-induced seizure was used to evaluate seizure susceptibility in the offspring. RESULTS: Spatial learning and avoidance memory significantly decreased in both male and female offspring of Pg LPS-exposed female rats, compared to the control offspring. Latency to reach seizure stages 1 and 2 significantly increased in the male offspring, but not the female offspring of Pg LPS-exposed female, compared to the control offspring. However, no significant difference was found in latency to reach stages 3-5. CONCLUSION: Pre-pregnancy exposure to Pg LPS could affect some behavioral functions in both male and female offspring intergenerationally.


Assuntos
Periodontite , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Lipopolissacarídeos/toxicidade , Masculino , Aprendizagem em Labirinto , Porphyromonas gingivalis , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Convulsões/induzido quimicamente , Fator de Necrose Tumoral alfa
9.
Medicine (Baltimore) ; 100(4): e24495, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530271

RESUMO

RATIONALE: Sevoflurane-induced seizures are most often caused by high concentrations of sevoflurane during anesthesia induction. However, in this case, we found a rare case of seizure-like movements caused by residual sevoflurane inside the anesthesia machine. Therefore, we propose that the detection of residual anesthesia-inhaled drugs should be included in pre-anesthesia checkout procedures. PATIENT CONCERNS: An 11-year-old girl with a history of epilepsy was scheduled for emergency appendectomy under general anesthesia. The patient presented with seizure-like movements caused by residual sevoflurane inside the anesthesia machine after pre-oxygenation during rapid sequence induction. DIAGNOSES: Based on the clinical presentation and previous history of seizures, sevoflurane-induced seizures were diagnosed. INTERVENTIONS: A washout procedure was performed by turning the oxygen flow up to 10L/min to wash out the residual sevoflurane from the anesthesia machine. OUTCOMES: The seizures ceased spontaneously, and the vital signs of the patient were stable during the washout procedure. Rapid sequence anesthesia induction and total intravenous anesthesia maintenance were uneventful. Surgery was performed as planned, and there were no postoperative problems. The patient was discharged after 4 days without complications and was well on follow-up. LESSONS: The check-up procedure of residual anesthesia-inhaled drugs inside the anesthesia machine should be included in the checkout design guidelines, or else the washout procedure should be performed in the pre-anesthesia checkout procedures.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Convulsões/induzido quimicamente , Sevoflurano/efeitos adversos , Anestesia Geral/efeitos adversos , Anestesia Geral/instrumentação , Criança , Feminino , Humanos
10.
Epilepsia ; 62(1): 238-249, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417274

RESUMO

OBJECTIVE: LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic. METHODS: Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR-101 was evaluated using seizure models induced by pentylenetetrazol and (+)-bicuculline. The ability of LMR-101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR-101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties. RESULTS: In the mouse study, LMR-101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR-101 completely inhibited pentylenetetrazol-induced seizures at a dose of 50 mg/kg and exhibited heavy sedation at 300 mg/kg. Propofol anesthetized all mice and only decreased the seizure rate at 25 mg/kg. LMR-101 also suppressed seizure behaviors evoked by (+)-bicuculline in mice in a dose-dependent manner. In the pilocarpine-induced SE model, LMR-101 significantly decreased the maximum seizure score and seizure duration in a dose-dependent manner. The median effective dose for LMR-101 was 14.30 mg/kg and 121.87 mg/kg to prevent and inhibit sustained SE, respectively. In binding assays, LMR-101 primarily inhibited tert-[35 S] butylbicyclophosphorothionate binding to γ-aminobutyric acid type A (GABAA ) receptors (half-maximal inhibitory concentration = 2.06 µmol·L-1 ), but it did not affect [3 H] flunitrazepam or [3 H] muscimol binding. SIGNIFICANCE: It is anticipated that LMR-101 might play an essential role in the clinical management of epilepsy and SE. LMR-101 also might bind to a novel target site on the GABAA receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABAA receptors.


Assuntos
Anticonvulsivantes/farmacologia , Propofol/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Convulsões/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Bicuculina/toxicidade , Eletroencefalografia , Antagonistas de Receptores de GABA-A/toxicidade , Hipnóticos e Sedativos/farmacologia , Camundongos , Agonistas Muscarínicos/toxicidade , Pentilenotetrazol/toxicidade , Fenóis/farmacologia , Pilocarpina/toxicidade , Propofol/análogos & derivados , Ratos , Receptores de GABA-A/metabolismo , Convulsões/induzido quimicamente , Estado Epiléptico/induzido quimicamente
13.
Epilepsy Behav ; 114(Pt A): 107652, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309429

RESUMO

INTRODUCTION: Epilepsy is a debilitating neurological condition characterized by spontaneous seizures as well as significant comorbid behavioral abnormalities. In addition to seizures, epileptic patients exhibit interictal spikes far more frequently than seizures, often, but not always observed in the same brain areas. The exact relationship between spiking and seizures as well as their respective effects on behavior are not well understood. In fact, spiking without overt seizures is seen in various psychiatric conditions including attention-deficit hyperactivity disorder. METHODS: In order to study the effects of spiking and seizures on behavior in an epileptic animal model, we used long-term video-electroencephalography recordings at six cortical recording sites together with behavioral activity monitoring. Animals received unilateral injections of tetanus toxin into either the somatosensory or motor cortex. RESULTS: Somatosensory cortex-injected animals developed progressive spiking ipsilateral to the injection site, while those receiving the injection into the motor cortex developed mostly contralateral spiking and spontaneous seizures. Animals with spiking but no seizures displayed a hyperactive phenotype, while animals with both spiking and seizures displayed a hypoactive phenotype. Not all spikes were equivalent as spike location strongly correlated with distinct locomotor behaviors including ambulatory distance, vertical movements, and rotatory movement. CONCLUSIONS: Together, our results demonstrate relationships between brain region-specific spiking, seizures, and behaviors in rodents that could translate into a better understanding for patients with epileptic behavioral comorbidities and other neuropsychiatric disorders.


Assuntos
Epilepsia , Animais , Encéfalo , Eletroencefalografia , Epilepsia/complicações , Humanos , Convulsões/induzido quimicamente , Córtex Somatossensorial
14.
Epilepsy Behav ; 115: 107659, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33334719

RESUMO

Transcranial focal stimulation (TFS) is a noninvasive neuromodulation strategy that reduces seizure activity in different experimental models. Nevertheless, there is no information about the effects of TFS in the drug-resistant phenotype associated with P-glycoprotein (Pgp) overexpression. The present study focused on determining the effects of TFS on Pgp expression after an acute seizure induced by 3-mercaptopropionic acid (MPA). P-glycoprotein expression was analyzed by western blot in the cerebral cortex and hippocampus of rats receiving 5 min of TFS (300 Hz, 50 mA, 200 µs, biphasic charge-balanced squared pulses) using a tripolar concentric ring electrode (TCRE) prior to administration of a single dose of MPA. An acute administration of MPA induced Pgp overexpression in cortex (68 ±â€¯13.4%, p < 0.05 vs the control group) and hippocampus (48.5 ±â€¯14%, p < 0.05, vs the control group). This effect was avoided when TFS was applied prior to MPA. We also investigated if TFS augments the effects of phenytoin in an experimental model of drug-resistant seizures induced by repetitive MPA administration. Animals with MPA-induced drug-resistant seizures received TFS alone or associated with phenytoin (75 mg/kg, i.p.). TFS alone did not modify the expression of the drug-resistant seizures. However, TFS combined with phenytoin reduced seizure intensity, an effect associated with a lower prevalence of major seizures (50%, p = 0.03 vs phenytoin alone). Our experiments demonstrated that TFS avoids the Pgp overexpression induced after an acute convulsive seizure. In addition, TFS augments the phenytoin effects in an experimental model of drug-resistant seizures. According with these results, it is indicated that TFS may represent a new neuromodulatory strategy to revert the drug-resistant phenotype.


Assuntos
Hipocampo , Convulsões , Subfamília B de Transportador de Cassetes de Ligação de ATP , Animais , Modelos Animais de Doenças , Eletrodos , Ratos , Convulsões/induzido quimicamente
15.
Epilepsy Behav ; 115: 107653, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33358679

RESUMO

Epileptic seizures are characterized by imbalanced inhibition-excitation cycle that triggers biochemical alterations responsible for jeopardized neuronal integrity. Conventional antiepileptic drugs (AEDs) have been the mainstay option for treatment and control; however, symptomatic control and potential to exacerbate the seizure condition calls for viable alternative to these chemical agents. In this context, natural product-based therapies have accrued great interest in recent years due to competent disease management potential and lower associated adversities. Cicuta virosa (CV) is one such herbal remedy that is used in traditional system of medicine against myriad of disorders including epilepsy. Homeopathic medicinal preparations (HMPs) of CV were assessed for their efficacy in pentylenetetrazole (PTZ)-induced acute and kindling models of epilepsy. CV HMPs increased the latency and reduced the duration of tonic-clonic phase in acute model while lowering the kindling score in the kindling model that signified their role in modulating GABAergic neurotransmission and potassium conductance. Kindling-induced impairment of cognition, memory, and motor coordination was ameliorated by the CV HMPs that substantiated their efficacy in imparting sustained neuronal fortification. Furthermore, biochemical evaluation showed attenuated oxidative stress load through reduced lipid peroxidation and strengthened free radical scavenging mechanism. Taken together, CV HMPs exhibited promising results in acute and kindling models and must be further assessed through molecular and epigenomic studies.


Assuntos
Cicuta , Excitação Neurológica , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Humanos , Estresse Oxidativo , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
16.
Epilepsy Behav ; 115: 107657, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33360400

RESUMO

OBJECTIVE: Adverse events (AEs) related to antiepileptic drugs (AEDs) may interfere with adequate dosing and patient adherence, leading to suboptimal seizure control, and relatedly, increased injuries, hospitalizations, and mortality. This study investigated the clinicodemographic factors associated with AEs related to AEDs as reported by the Liverpool Adverse Events Profile (LAEP), and explored the ability of LAEP to discriminate between epilepsy and psychogenic nonepileptic seizures (PNES). We hypothesized that female sex, mood disorders, AED-polytherapy, duration, and severity of epilepsy are associated with increased endorsement of AEs related to AEDs, and that endorsement of AEs related to AEDs would significantly differ between epilepsy and PNES patients. METHODS: We prospectively enrolled adult patients admitted to two inpatient video-electroencephalogram monitoring units. Clinicodemographic variables and psychometric measures of depression, anxiety, and cognitive function were recorded. Patient-reported AE endorsement was obtained using the LAEP, which was reduced to four latent domains using exploratory structural equation modeling. General linear models identified variables associated with each domain. Logistic regression determined the ability of LAEP scores to differentiate between epilepsy and PNES. RESULTS: 311 patients met inclusion criteria. Mean age was 38 years and 56% of patients were female. Network analysis demonstrated strong relationships between depression and anxiety with physical, sleep, psychiatric, and dermatological AE endorsement. Depression, female sex, and AED polytherapy were associated with greater AE endorsement. Epilepsy, compared to PNES, was associated with lower AE endorsement. Fewer prescribed AEDs and greater reported physical AE endorsement were associated with PNES diagnosis. SIGNIFICANCE: There is a strong relationship between patient-reported AEs and psychiatric symptomatology. Those with PNES paradoxically endorse greater physical AEs despite receiving fewer AEDs. Patients who endorse AEs in clinical practice should be screened for comorbid depression or anxiety and treated accordingly.


Assuntos
Anticonvulsivantes , Epilepsia , Adulto , Anticonvulsivantes/efeitos adversos , Ansiedade/induzido quimicamente , Transtornos de Ansiedade/tratamento farmacológico , Eletroencefalografia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
17.
Neurosci Lett ; 743: 135560, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33359047

RESUMO

Epilepsy is a chronic neurological condition that affects 1%-2% of the world population. Although research about the disease is advancing and a wide variety of drugs is available, about 30 % of patients have refractory epilepsy which cannot be controlled with the most common drugs. This highlights the need for a better understanding of the disorder and new types of treatment for it. Against this backdrop, a growing body of evidence has reported that inflammation may play a role both in the origin and in the progression of seizures. It has shown a tendency to be both the root and the result of epilepsy. This investigation aimed to assess the impact of prednisolone, a steroidal anti-inflammatory drug, in an animal model of pentylenetetrazole (PTZ)-induced seizures, at 1 mg/kg and 5 mg/kg doses. We also examined the degree of seizure severity and the modulation of pro-inflammatory cytokines in the treated animals. Four treatment groups were used (saline, diazepam, prednisolone 1 mg/kg, and prednisolone 5 mg/kg) and, in addition to their own daily treatments, subconvulsant doses of pentylenetetrazole (25 mg/kg) were administered every other day during a test protocol that lasted 14 days. After treatment, the cytokines interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured in the animals' sera, hippocampi, and prefrontal cortices. Animals treated with prednisolone presented less severe seizures than the animals in the saline group, and there was a decrease in pro-inflammatory cytokine levels in central structures, but not peripheral ones. In short, an animal model of chemically-induced epileptic seizures was used, in which the animals were treated with doses of prednisolone, and these animals presented less severe seizures than the negative control group (saline), in addition to showing decreased levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, in the hippocampi and prefrontal cortices, but not the sera.


Assuntos
Anti-Inflamatórios/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Locomoção/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Prednisolona/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Mediadores da Inflamação/metabolismo , Locomoção/fisiologia , Masculino , Prednisolona/farmacologia , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/metabolismo , Resultado do Tratamento
18.
Int J Nanomedicine ; 15: 6339-6353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922005

RESUMO

Introduction: Epilepsy is a chronic neurological condition characterized by behavioral, molecular, and neurochemical alterations. Current antiepileptic drugs are associated with various adverse impacts. The main goal of the current study is to investigate the possible anticonvulsant effect of selenium nanoparticles (SeNPs) against pentylenetetrazole (PTZ)-mediated epileptic seizures in mice hippocampus. Sodium valproate (VPA) was used as a standard anti-epileptic drug. Methods: Mice were assigned into five groups (n=15): control, SeNPs (5 mg/kg, orally), PTZ (60 mg/kg, intraperitoneally), SeNPs+PTZ and VPA (200 mg/kg)+PTZ. All groups were treated for 10 days. Results: PTZ injection triggered a state of oxidative stress in the hippocampal tissue as represented by the elevated lipoperoxidation, heat shock protein 70 level, and nitric oxide formation while decreased glutathione level and antioxidant enzymes activity. Additionally, the blotting analysis showed downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the epileptic mice. A state of neuroinflammation was recorded following the developed seizures represented by the increased pro-inflammatory cytokines. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions. At the neurochemical level, acetylcholinesterase activity and monoamines content were decreased in the epileptic mice, accompanied by high glutamate and low GABA levels in the hippocampal tissue. However, SeNP supplementation was found to delay the onset and decreased the duration of tonic, myoclonic, and generalized seizures following PTZ injection. Moreover, SeNPs were found to provide neuroprotection through preventing the development of oxidative challenge via the upregulation of Nrf2 and HO-1, inhibiting the inflammatory response and apoptotic cascade. Additionally, SeNPs reversed the changes in the activity and levels of neuromodulators following the development of epileptic seizures. Conclusion: The obtained results suggest that SeNPs could be used as a promising anticonvulsant drug due to its potent antioxidant, anti-inflammatory, and neuromodulatory activities.


Assuntos
Nanopartículas/química , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Convulsões/tratamento farmacológico , Selênio/uso terapêutico , Aminoácidos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Apoptose/efeitos dos fármacos , Colinérgicos/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Camundongos , Nanopartículas/administração & dosagem , Neurônios/efeitos dos fármacos , Neurotransmissores/metabolismo , Oxirredução , Pentilenotetrazol , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Selênio/administração & dosagem , Selênio/farmacologia
19.
Emerg Med Clin North Am ; 38(4): 841-856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981621
20.
Nihon Yakurigaku Zasshi ; 155(5): 284-288, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879165

RESUMO

In the drug development in pharmaceuticals, development of drugs may be discontinued due to the toxicity and clinical side effect, therefore, safety assessment is one of the important factors in drug development. Consortium for Safety Assessment using Human Cells (CSAHi) has been launched for developing and standardizing a toxicity evaluation system for development of drug using human iPS cell differentiated cells. CSAHi focuses on hepato-, cardio-, and neuro-toxicities as important toxicity organs which are attributed to the causes of discontinuation of drug development. In neurotoxicity, seizure is an important finding because of high frequency expression in nonclinical. Multi-electrode array (MEA) systems have recently attracted attention as useful for evaluating seizure risk because they can non-invasively measure the electrophysiological activities of neural networks. We are evaluating the electrophysiological responses to several seizure compounds using MEA in cultured hiPSC-derived neurons. It is important to establish an analytical method to detecting seizure-like activities. We have focused the establish of the effective analysis parameters for detecting seizure risk. We identify to be separate the responses between seizure-positive and seizure-negative compounds using principal component analysis of 10 analysis parameters. In addition, we could separate the mechanism of action of the seizure-positive compounds by principal component analysis and cluster analysis using 10 parameters. It is considered that principal component analysis or cluster analysis could not only assess the seizure risk but also classify mechanism of action by in vitro MEA system using human iPS cell-derived neurons.


Assuntos
Células-Tronco Pluripotentes Induzidas , Potenciais de Ação , Células Cultivadas , Humanos , Microeletrodos , Neurônios , Convulsões/induzido quimicamente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...