Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.628
Filtrar
1.
Medicine (Baltimore) ; 98(44): e17797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689857

RESUMO

RATIONALE: Acute necrotizing encephalopathy (ANE) is a rapidly progressing disease associated with frequent neurologic sequelae and has poor prognosis. Currently, the diagnosis and treatment of ANE rely on neuroradiologic findings and offering supportive care. Here, we report the successful treatment of a teenager diagnosed with ANE using combination of high-dose methylprednisolone and oseltamivir. PATIENT CONCERNS: The patient, a 15-year-old female, presented with impaired consciousness and seizures secondary to acute upper respiratory tract infection. A series of brain magnetic resonance images (MRIs) were obtained toward establishing a possible diagnosis. DIAGNOSIS: Based on the history of presenting illness and subsequent brain MRI scans, the patient was diagnosed to be suffering from ANE. INTERVENTIONS: Following the diagnosis, the patient was placed on therapy comprising of high-dose methylprednisolone and oseltamivir. OUTCOMES: After treatment with methylprednisolone and oseltamivir for 15 days, the patient recovered nearly completely from ANE as confirmed by subsequent brain MRI scans. No complications or other emerging clinical symptoms were noted for the duration of follow-up that lasted 6 months. LESSONS: Contrary to common reports, ANE can occur beyond pediatric populations and its treatment should not be restricted to supportive care. Our case suggests that the use of high-dose corticosteroids and oseltamivir leads to promising prognosis.


Assuntos
Encéfalo/diagnóstico por imagem , Encefalite Viral/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Infecções Respiratórias/complicações , Convulsões/diagnóstico por imagem , Adolescente , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Encéfalo/patologia , Encéfalo/virologia , China , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Feminino , Humanos , Necrose/diagnóstico por imagem , Necrose/virologia , Oseltamivir/uso terapêutico , Prognóstico , Infecções Respiratórias/virologia , Convulsões/patologia , Convulsões/virologia
3.
Nat Methods ; 16(8): 763-770, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308547

RESUMO

Current techniques for monitoring GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in vertebrates, cannot follow transients in intact neural circuits. To develop a GABA sensor, we applied the design principles used to create the fluorescent glutamate receptor iGluSnFR. We used a protein derived from a previously unsequenced Pseudomonas fluorescens strain and performed structure-guided mutagenesis and library screening to obtain intensity-based GABA sensing fluorescence reporter (iGABASnFR) variants. iGABASnFR is genetically encoded, detects GABA release evoked by electric stimulation of afferent fibers in acute brain slices and produces readily detectable fluorescence increases in vivo in mice and zebrafish. We applied iGABASnFR to track mitochondrial GABA content and its modulation by an anticonvulsant, swimming-evoked, GABA-mediated transmission in zebrafish cerebellum, GABA release events during interictal spikes and seizures in awake mice, and found that GABA-mediated tone decreases during isoflurane anesthesia.


Assuntos
Técnicas Biossensoriais/métodos , Encéfalo/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/metabolismo , Imagem Molecular/métodos , Neurônios/metabolismo , Ácido gama-Aminobutírico/metabolismo , Anestesia , Animais , Animais Geneticamente Modificados , Feminino , Proteínas de Fluorescência Verde/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Convulsões/metabolismo , Convulsões/patologia , Peixe-Zebra
4.
Nervenarzt ; 90(8): 773-780, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31243507

RESUMO

Epilepsy is a frequent and disabling neurological disease with a significant burden for patients and their relatives worldwide. Epileptogenesis is understood as the plastic process that after an insult (in acquired epilepsies) finally leads to seizures with a latent period. In some cases, epileptogenesis has been clarified down to the molecular level. In parallel, the discovery of genetic defects has decisively contributed to unravel epileptic disease mechanisms. Both research directions have enabled first personalized treatment options. In addition, genetic variants associated with epilepsy can not only directly cause seizures but likely also induce an epileptogenic process (similar as in acquired epilepsies) and interact with developmental processes of the brain, finally leading to the typical age-dependent manifestation of genetic epilepsy syndromes. This article describes these correlations and the consequences for personalized treatment possibilities.


Assuntos
Epilepsia , Medicina de Precisão , Encéfalo/patologia , Epilepsia/terapia , Humanos , Convulsões/patologia , Convulsões/terapia
5.
J Vet Diagn Invest ; 31(4): 576-580, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31018782

RESUMO

Gliomas are common primary central nervous system neoplasms of dogs and cats, but atypical glioma subtypes are rare. Herein we report an angiocentric astrocytoma in a 15-y-old spayed female domestic shorthaired cat that was euthanized after therapy-resistant seizures. Gross anatomic changes consisted of swelling of the rostral leptomeninges over the olfactory bulbs and rostral telencephalon. Histologically, polygonal-to-elongate atypical neoplastic cells were arranged along perivascular spaces within these areas. Neoplastic cells were positive for glial fibrillary acidic protein, S100 protein, and vimentin. Ultrastructurally, round-to-elongate neoplastic cells emitting long processes with aggregates of intermediary filaments expanded and occupied the spaces between the vascular basement membrane and the glia limitans; nuclei had marginal and central heterochromatin. Tight junctions connected the plasma membrane of neighboring cells. The cell morphology, immunohistochemistry, and ultrastructural findings were consistent with an astrocytoma; the exclusive perivascular arrangement of neoplastic cells with no parenchymal mass warranted the diagnosis of angiocentric astrocytoma.


Assuntos
Astrocitoma/veterinária , Neoplasias Encefálicas/veterinária , Doenças do Gato/patologia , Animais , Astrocitoma/diagnóstico , Astrocitoma/patologia , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Gatos , Feminino , Proteína Glial Fibrilar Ácida , Proteínas S100 , Convulsões/patologia , Convulsões/veterinária , Vimentina
6.
Lupus ; 28(5): 685-694, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31018814

RESUMO

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an important cause of morbidity and mortality. We undertook this observational retrospective study of patients with NPSLE who had brain magnetic resonance imaging (MRI) to determine the indications for MRI and the correlation of clinical and laboratory findings with MRI. We identified 83 NPSLE patients (84.3% women) seen at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, between June 2003 and May 2017. The mean age at SLE diagnosis was 26.24 ± 12.81 years and the median interval to NPSLE was 11.0 (interquartile range, 4.0-39.0) months. The most common indications for MRI were seizures (45.8%), psychosis (18.1%) and cerebrovascular disease (18.1%). The MRI was abnormal in 68 (81.9%) with small-vessel disease in 65 (78.3%) and large-vessel disease in eight (9.6%). The small-vessel abnormalities were white-matter hyperintensities (WMH) (59.0%), atrophy (55.4%) and lacunae (4.6%). Our patients had high disease activity at NPSLE. Cerebrovascular disease was associated with an abnormal MRI ( p = 0.018) and large-vessel disease ( p = 0.014) on MRI. Our NPSLE patients were younger and had high disease activity, and seizures were more common compared with other studies. The most common MRI abnormalities were WMH and cortical atrophy, in agreement with other studies.


Assuntos
Encéfalo/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Adolescente , Adulto , Atrofia , Encéfalo/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/patologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Imagem por Ressonância Magnética , Masculino , Fenótipo , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/patologia , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/patologia , África do Sul , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
7.
Oxid Med Cell Longev ; 2019: 1327986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019649

RESUMO

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures due to an imbalance between cerebral excitability and inhibition, with a tendency towards uncontrolled excitability. Epilepsy has been associated with oxidative and nitrosative stress due to prolonged neuronal hyperexcitation and loss neurons during seizures. The experimental animal models report level of ATP diminished and increase in lipid peroxidation, catalase, and glutathione altered activity in the brain. We studied the immunohistochemical expression and localization of antioxidant enzymes GPx, SOD, and CAT in the rat brains treated with KA and PTZ. A significant decrease was observed in the number of immunoreactive cells to GPx, without significant changes for SOD and CAT in KA-treated rats, and decrease in the number of immunoreactive cells to SOD, without significant changes for GPx and only CAT in PTZ-treated rats. Evident immunoreactivity of GPx, SOD, and CAT was observed mainly in astrocytes and neurons of the hippocampal brain region in rats exposed at KA; similar results were observed in rats treated with PTZ at the first hours. These results provide evidence supporting the role of activation of the Nrf2 antioxidant system pathway against oxidative stress effects in the experimental models of epileptic seizures.


Assuntos
Imuno-Histoquímica/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Convulsões/enzimologia , Convulsões/patologia , Animais , Antioxidantes/metabolismo , Comportamento Animal , Hipocampo/patologia , Ácido Caínico , Masculino , Modelos Biológicos , Pentilenotetrazol , Ratos Wistar
8.
Biomed Pharmacother ; 114: 108683, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30947016

RESUMO

OBJECTIVE: This study is conducted to explore the role of microRNA-223 (miR-223) in brain injury and apoptosis of hippocampal neurons through the NLRP3-Caspase-1 signaling pathway in febrile seizure (FS) rats. METHODS: The models of FS were induced in rats by hot water-bath, which were stereotactically injected with miR-223 mimics and mimics negative control (NC) to perturb the expression of miR-223. A series of experiments was conducted to find out the potential mechanisms of miR-223 on convulsion attack, learning and memory ability, pathological injury of hippocampal neurons, inflammatory injury, apoptosis of hippocampal neurons in FS rats. Besides, the targeting relationship between miR-223 and NLRP3 was also verified. RESULTS: Low expression of miR-223 was found in hippocampus tissues of FS rats. Up-regulation of miR-223 alleviated convulsion attack and improved learning and memory ability, while inhibiting pathological injury of hippocampal neurons and inflammatory injury in FS rats. Up-regulation of miR-223 promoted the survival of hippocampal neurons and inhibited their apoptosis in FS rats. MiR-223 inhibited the activation of NLRP3-Caspase-1 signaling pathway in hippocampus tissues of FS rats by inhibiting NLRP3. CONCLUSION: The inhibited expression of miR-223 after FS may participate in the activation of the NLRP3-Caspase-1 signaling pathway, resulting in brain injury and apoptosis of hippocampal neurons in rat models of FS.


Assuntos
Apoptose/genética , Lesões Encefálicas/genética , Caspase 1/genética , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Convulsões Febris/genética , Regulação para Cima/genética , Animais , Lesões Encefálicas/patologia , Hipocampo/patologia , Aprendizagem/fisiologia , Memória/fisiologia , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Convulsões/genética , Convulsões/patologia , Transdução de Sinais/genética , Ativação Transcricional/genética
9.
Molecules ; 24(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013866

RESUMO

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.


Assuntos
Ansiolíticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Canabidiol/uso terapêutico , Cannabis/química , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Ansiolíticos/efeitos adversos , Ansiolíticos/química , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/química , Antipsicóticos/efeitos adversos , Antipsicóticos/química , Canabidiol/efeitos adversos , Canabidiol/química , Ensaios Clínicos como Assunto , Epilepsia/patologia , Epilepsia/fisiopatologia , Humanos , Convulsões/patologia , Convulsões/fisiopatologia
10.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022879

RESUMO

Epilepsy is a prevalent neurological disorder that was reported to affect about 56 million people in the world. Approximately one-third of the epileptic patients that suffer from seizures do not receive effective medical treatment. The aim of this study was to determine the potential anticonvulsant activities of Baldrinal (BAL) with a mouse model of pilocarpine (PILO)-induced epilepsy. The mice were treated with different doses of BAL or sodium valproate prior to PILO injection. Spontaneous and evoked seizures were evaluated from EEG recordings, and their severity was tested by the Racine scale. In addition, the brain tissues were analyzed for histological changes, and the in situ levels of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) were also measured. Activation of astrocytes in the hippocampus was measured. PILO-treated mice showed a significant increase in Glu levels, which was restored by BAL. In addition, BAL treatment also reduced the rate of seizures in the epileptic mice, and ameliorated the increased levels of NMDAR1, BDNF, IL-1ß and TNF-α. Taken together, BAL has a potential antiepileptic effect, which may be mediated by reducing the inflammatory response in the PILO-induced brain and restoring the balance of GABAergic and glutamatergic neurons.


Assuntos
Encéfalo/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Iridoides/administração & dosagem , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/administração & dosagem , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/patologia , Ácido Glutâmico/metabolismo , Humanos , Camundongos , Pilocarpina/toxicidade , Convulsões/induzido quimicamente , Convulsões/patologia , Ácido gama-Aminobutírico/metabolismo
11.
Int Braz J Urol ; 45(3): 629-633, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30912892

RESUMO

Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Embrionárias de Células Germinativas/secundário , Convulsões/patologia , Neoplasias Testiculares/patologia , Neoplasias Encefálicas/terapia , Gonadotropina Coriônica Humana Subunidade beta/sangue , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/terapia , Convulsões/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/terapia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto Jovem , alfa-Fetoproteínas/análise
12.
J Neuroinflammation ; 16(1): 66, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922332

RESUMO

BACKGROUND: Microglia are important for secreting chemical mediators of inflammatory responses in the central nervous system. Interleukin (IL)-10 and IL-1ß secreted by glial cells support neuronal functions, but the related mechanisms remain vague. Our goal was to demonstrate the efficacy of IL-10 in suppressing IL-1ß and in inflammasome activation in mice with epileptic seizure based on an epileptic-seizure mouse model. METHODS: In this study, mice in which epileptic seizures were induced by administering picrotoxin (PTX) were used as a case group, and mice injected with saline were employed as the control group. The expression of nucleic acids, cytokines, or signaling pathways was detected by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blotting. RESULTS: Our results demonstrated that IL-10 inhibits IL-1ß production through two distinct mechanisms: (1) Treatment with lipopolysaccharides (LPS) results in IL-10 overexpression in microglia and reduced NLRP3 inflammasome activity, thus inhibiting caspase-1-related IL-1ß maturation; (2) next, autocrine IL-10 was found to subsequently promote signal transducer and activator of transcription-3 (STAT-3), reducing amounts of pro-IL-1ß. CONCLUSIONS: Our results indicate that IL-10 is potentially effective in the treatment of inflammation encephalopathy, and suggest the potential usefulness of IL-10 for treating autoimmune or inflammatory ailments.


Assuntos
Interleucina-10/farmacologia , Interleucina-1beta/metabolismo , Microglia/metabolismo , Convulsões/patologia , Animais , Encéfalo/patologia , Células Cultivadas , Convulsivantes/toxicidade , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Ácidos Nucleicos/genética , Ácidos Nucleicos/metabolismo , Picrotoxina/toxicidade , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT3/metabolismo , Convulsões/induzido quimicamente , Convulsões/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
13.
Epilepsy Res ; 151: 67-74, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30836238

RESUMO

Extracellular proteolysis initiated by the binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) regulates the development of inhibitory neuronal circuits in the cerebral cortex and tissue remodeling after epileptogenic brain injury. To study the function of different components of the uPA-uPAR system on behavior and epileptogenesis, and to complement our previous studies on naïve and injured mice deficient in the uPA-encoding gene Plau or the uPAR-encoding gene Plaur, we analyzed the behavioral phenotype, seizure susceptibility, and perineuronal nets surrounding parvalbumin-positive inhibitory interneurons in Plau and Plaur (double knockout dKO) mice. In a climbing test, dKO mice showed reduced interest towards the environment as compared with Wt mice (p < 0.01). In a social approach test, however, dKO mice spent more time than Wt mice exploring the compartment containing a stranger mouse than the empty compartment (p < 0.05). Moreover, in a social interaction test, dKO mice exhibited increased contact time (p < 0.01). Compared with Wt mice, the dKO mice also had a longer single contact duration (p < 0.001) with the stranger mouse. In the elevated plus-maze, grooming, and marble burying tests, the anxiety level of dKO mice did not differ from that of Wt mice. Rearing time in an exploratory activity test, and spatial learning and memory in the Morris swim navigation task were also comparable between dKO and Wt mice. In the pentylenetetrazol (PTZ) seizure-susceptibility test, dKO mice had a shorter latency to the first epileptiform spike (p = 0.0001) and a greater total number of spikes (p < 0.001) than Wt mice. The dKO genotype did not affect the number of cortical perineuronal nets. Our findings indicate that Plau/Plaur-deficiency leads to a more social phenotype toward other mice with diminished interest in the surrounding environment, and increased seizure susceptibility.


Assuntos
Regulação da Expressão Gênica/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/deficiência , Convulsões/metabolismo , Comportamento Social , Ativador de Plasminogênio Tipo Uroquinase/deficiência , Animais , Ansiedade/etiologia , Ansiedade/genética , Aprendizagem da Esquiva/fisiologia , Ondas Encefálicas/efeitos dos fármacos , Ondas Encefálicas/genética , Convulsivantes/toxicidade , Modelos Animais de Doenças , Suscetibilidade a Doenças/induzido quimicamente , Suscetibilidade a Doenças/fisiopatologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Asseio Animal/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pentilenotetrazol/toxicidade , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Convulsões/induzido quimicamente , Convulsões/patologia , Ativador de Plasminogênio Tipo Uroquinase/genética
14.
Epilepsy Res ; 153: 19-27, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30927681

RESUMO

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a result of interplay between psychological, immune, neurological and genetic factors, manifested by variety of urological, as well as brain-related symptoms. However, its relation with brain excitability has not been addressed. herefore, our aim was to assess susceptibility to seizures in rats with CP/CPPS. We induced CP/CPPS in adult rats by intraprostatic injection of 3% λ-carrageenan. Sham operated rats served as controls (0.9% NaCl, Sham). On day 7 upon injection, rats were treated with lindane (4 mg/kg) and observed for convulsive behavior (seizure incidence, latency and severity) and EEG manifestations (number and duration of ictal periods). Interleukin levels (IL-1ß and IL-6) were measured in prostate, hippocampus, thalamus and cerebral cortex. Scrotal skin mechanical pain thresholds were determined and prostates were histologically evaluated. Animals with CP/CPPS showed significantly higher incidence, decreased latency time and augmented severity of lindane-induced seizures compared with Sham group. EEG revealed increased number of ictal periods in CP/CPPS rats. Higher levels of IL-1ß and IL-6 were determined in the thalamus and cortex in CP/CPPS animals vs. Sham. IL-1ß level was higher and IL-6 was lower in prostates from CP/CPPS animals comparing to Sham. CP/CPPS development was verified by histological findings of nonbacterial inflammation in the prostates, as well as by significantly decreased scrotal pain threshold in CP/CPPS animals. On the basis of this research, we concluded that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with increased level of IL-1ß and IL-6 in the cortex and thalamus.


Assuntos
Encéfalo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Dor Pélvica/complicações , Convulsões/etiologia , Convulsões/patologia , Animais , Doença Crônica , Modelos Animais de Doenças , Suscetibilidade a Doenças , Eletroencefalografia , Hexaclorocicloexano/toxicidade , Inseticidas/toxicidade , Masculino , Medição da Dor , Limiar da Dor/fisiologia , Dor Pélvica/etiologia , Próstata/patologia , Prostatite/complicações , Ratos , Ratos Wistar , Estatísticas não Paramétricas
15.
eNeuro ; 6(1)2019.
Artigo em Inglês | MEDLINE | ID: mdl-30895220

RESUMO

Seizures are characterized by hypersynchronization of neuronal networks. Understanding these networks could provide a critical window for therapeutic control of recurrent seizure activity, i.e., epilepsy. However, imaging seizure networks has largely been limited to microcircuits in vitro or small "windows" in vivo. Here, we combine fast confocal imaging of genetically encoded calcium indicator (GCaMP)-expressing larval zebrafish with local field potential (LFP) recordings to study epileptiform events at whole-brain and single-neuron levels in vivo. Using an acute seizure model (pentylenetetrazole, PTZ), we reliably observed recurrent electrographic ictal-like events associated with generalized activation of all major brain regions and uncovered a well-preserved anterior-to-posterior seizure propagation pattern. We also examined brain-wide network synchronization and spatiotemporal patterns of neuronal activity in the optic tectum microcircuit. Brain-wide and single-neuronal level analysis of PTZ-exposed and 4-aminopyridine (4-AP)-exposed zebrafish revealed distinct network dynamics associated with seizure and non-seizure hyperexcitable states, respectively. Neuronal ensembles, comprised of coactive neurons, were also uncovered during interictal-like periods. Taken together, these results demonstrate that macro- and micro-network calcium motifs in zebrafish may provide a greater understanding of epilepsy.


Assuntos
Encéfalo/fisiopatologia , Cálcio/metabolismo , Convulsões/fisiopatologia , Animais , Animais Geneticamente Modificados , Encéfalo/patologia , Sincronização Cortical , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Pentilenotetrazol , Convulsões/patologia , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
16.
Brain ; 142(2): 391-411, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30689758

RESUMO

Approximately one-quarter of patients with mitochondrial disease experience epilepsy. Their epilepsy is often severe and resistant towards conventional antiepileptic drugs. Despite the severity of this epilepsy, there are currently no animal models available to provide a mechanistic understanding of mitochondrial epilepsy. We conducted neuropathological studies on patients with mitochondrial epilepsy and found the involvement of the astrocytic compartment. As a proof of concept, we developed a novel brain slice model of mitochondrial epilepsy by the application of an astrocytic-specific aconitase inhibitor, fluorocitrate, concomitant with mitochondrial respiratory inhibitors, rotenone and potassium cyanide. The model was robust and exhibited both face and predictive validity. We then used the model to assess the role that astrocytes play in seizure generation and demonstrated the involvement of the GABA-glutamate-glutamine cycle. Notably, glutamine appears to be an important intermediary molecule between the neuronal and astrocytic compartment in the regulation of GABAergic inhibitory tone. Finally, we found that a deficiency in glutamine synthetase is an important pathogenic process for seizure generation in both the brain slice model and the human neuropathological study. Our study describes the first model for mitochondrial epilepsy and provides a mechanistic insight into how astrocytes drive seizure generation in mitochondrial epilepsy.


Assuntos
Astrócitos/patologia , Astrócitos/fisiologia , Epilepsia do Lobo Temporal/patologia , Mitocôndrias/patologia , Doenças Mitocondriais/patologia , Convulsões/patologia , Adulto , Idoso , Animais , Epilepsia do Lobo Temporal/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Convulsões/metabolismo , Adulto Jovem
17.
Biochim Biophys Acta Mol Cell Res ; 1866(7): 1137-1150, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30659848

RESUMO

Orai proteins form highly selective Ca2+ release-activated channels (CRACs). They play a critical role in store-operated Ca2+ entry (SOCE; i.e., the influx of external Ca2+ that is induced by the depletion of endoplasmic reticulum Ca2+ stores). Of the three Orai homologs that are present in mammals (Orai1-3), the physiological function of Orai1 is the best described. CRACs are formed by both homomeric assemblies and heteromultimers of Orais. Orai1 and Orai2 can form heteromeric channels that differ in conductivity during SOCE, depending on their Orai1-to-Orai2 ratio. The present study explored the potential consequences of ORAI1 overexpression in neurons where the dominant isoform is Orai2. We established the Tg(ORAI1)Ibd transgenic mouse line that overexpresses ORAI1 in brain neurons. We observed seizure-like symptoms in aged (≥15-month-old) female mice but not in males of the same age. The application of kainic acid and bicuculline to slices that were isolated from 8-month-old (±1 month) female Tg(ORAI1)Ibd mice revealed a significantly lower frequency of interictal bursts compared with samples that were isolated from wildtype mice. No differences were observed in male mice of a similar age. A battery of behavioral tests showed that context recognition decreased only in female transgenic mice. The phenotype that was observed in female mice suggests that ORAI1 overexpression may affect neuronal activity in a sex-dependent manner. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.


Assuntos
Comportamento Animal , Ondas Encefálicas , Encéfalo/metabolismo , Neurônios/metabolismo , Proteína ORAI1/biossíntese , Proteína ORAI2/metabolismo , Convulsões/metabolismo , Animais , Encéfalo/patologia , Feminino , Camundongos , Camundongos Transgênicos , Neurônios/patologia , Proteína ORAI1/genética , Proteína ORAI2/genética , Convulsões/genética , Convulsões/patologia , Convulsões/fisiopatologia
18.
Epilepsy Res ; 151: 1-6, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30669043

RESUMO

Lycopene (LCP) is a carotenoid that protects against many diseases by alleviating oxidative stress. However, the effect of LCP on epileptic seizures has not been examined well in previous studies. In the current work, we employed kainic acid (KA) to induce experimental epileptic seizures in mice, and investigated the function of LCP during this process. We found that the onset and extent of KA-induced seizures were alleviated in LCP-pretreated mice. Nissl staining of hippocampus showed that the granule cell dispersion lesion induced by KA was improved by the LCP treatment. Additionally, we analyzed the oxidative stress levels in mice and found that LCP elevated SOD activity and suppressed MDA level in KA-induced seizures. Moreover, the expression of GABA receptors was influenced by LCP treatment. LCP suppressed the upregulation of gabrb2 and gabrb3 induced by KA, whereas it enhanced the expression of gabrb1. Results suggested that LCP plays a protective function in KA-induced seizures. Hence, it may be a potential functional food alternative for controlling and treating epileptic seizures.


Assuntos
Antioxidantes/administração & dosagem , Licopeno/administração & dosagem , Convulsões/prevenção & controle , Animais , Piscadela/efeitos dos fármacos , Modelos Animais de Doenças , Esquema de Medicação , Agonistas de Aminoácidos Excitatórios/toxicidade , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Ácido Caínico/toxicidade , Malondialdeído , Camundongos , RNA Mensageiro/metabolismo , Receptores de GABA/genética , Receptores de GABA/metabolismo , Convulsões/induzido quimicamente , Convulsões/patologia , Comportamento Estereotipado/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fatores de Tempo
19.
Int J Mol Sci ; 20(2)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669615

RESUMO

Theiler's murine encephalomyelitis virus (TMEV), a naturally occurring, enteric pathogen of mice is a Cardiovirus of the Picornaviridae family. Low neurovirulent TMEV strains such as BeAn cause a severe demyelinating disease in susceptible SJL mice following intracerebral infection. Furthermore, TMEV infections of C57BL/6 mice cause acute polioencephalitis initiating a process of epileptogenesis that results in spontaneous recurrent epileptic seizures in approximately 50% of affected mice. Moreover, C3H mice develop cardiac lesions after an intraperitoneal high-dose application of TMEV. Consequently, TMEV-induced diseases are widely used as animal models for multiple sclerosis, epilepsy, and myocarditis. The present review summarizes morphological lesions and pathogenic mechanisms triggered by TMEV with a special focus on the development of hippocampal degeneration and seizures in C57BL/6 mice as well as demyelination in the spinal cord in SJL mice. Furthermore, a detailed description of innate and adaptive immune responses is given. TMEV studies provide novel insights into the complexity of organ- and mouse strain-specific immunopathology and help to identify factors critical for virus persistence.


Assuntos
Doenças dos Animais/virologia , Infecções por Cardiovirus/veterinária , Theilovirus/fisiologia , Imunidade Adaptativa , Doenças dos Animais/imunologia , Doenças dos Animais/patologia , Doenças dos Animais/transmissão , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Humanos , Imunidade Inata , Camundongos , Esclerose Múltipla/etiologia , Esclerose Múltipla/patologia , Miocardite/etiologia , Miocardite/patologia , Miocardite/fisiopatologia , Convulsões/etiologia , Convulsões/patologia , Convulsões/fisiopatologia , Tropismo Viral
20.
Behav Brain Res ; 363: 135-144, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30684511

RESUMO

Tuberous sclerosis complex (TSC) is a rare disease caused by mutations in the TSC1 or TSC2 genes and is characterized by widespread tumour growth, intractable epilepsy, cognitive deficits and autistic behaviour. CBD has been reported to decrease seizures and inhibit tumour cell progression, therefore we sought to determine the influence of CBD on TSC pathology in zebrafish carrying a nonsense mutation in the tsc2 gene. CBD treatment from 6 to 7 days post-fertilization (dpf) induced significant anxiolytic actions without causing sedation. Furthermore, CBD treatment from 3 dpf had no impact on tsc2-/- larvae motility nor their survival. CBD treatment did, however, reduce the number of phosphorylated rpS6 positive cells, and their cross-sectional cell size. This suggests a CBD mediated suppression of mechanistic target of rapamycin (mTOR) activity in the tsc2-/- larval brain. Taken together, these data suggest that CBD selectively modulates levels of phosphorylated rpS6 in the brain and additionally provides an anxiolytic effect. This is pertinent given the alterations in mTOR signalling in experimental models of TSC. Additional work is necessary to identify upstream signal modulation and to further justify the use of CBD as a possible therapeutic strategy to manage TSC.


Assuntos
Canabidiol/farmacologia , Proteína S6 Ribossômica/efeitos dos fármacos , Esclerose Tuberosa/tratamento farmacológico , Animais , Encéfalo/metabolismo , Canabidiol/metabolismo , Canabinoides/metabolismo , Canabinoides/farmacologia , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Locomoção/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Convulsões/patologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Esclerose Tuberosa/fisiopatologia , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/efeitos dos fármacos , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA