RESUMO
BACKGROUND This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats. MATERIAL AND METHODS The rats were randomly divided into 4 groups: (1) the Control group (rats without any treatment); (2) the Sham group (rats received electrode implantation but without electrical stimulation); (3) the SSSE group (rats received electrode implantation and additional electrical stimulation); and (4) the SSSE+MB group (rats received 1 mg/kg MB intraperitoneal injection 5 min after SSSE). SSSE models were established by prolonged BLA stimulation. The severities of SSSE were assessed by the number of separate seizures and the accumulated time of seizures. The variations of malondialdehyde/glutathione (MDA/GSH) were assessed 24 h after the establishment of SSSE. Nissl staining was performed to detect the surviving neurons in hippocampal CA1 and CA3 regions, and Western blotting assays were used to detect Caspase-3 (CASP3), B cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX). RESULTS Compared with the SSSE group, treatment with MB (1) markedly reduced the number and accumulated time of seizure activities; (2) significantly attenuated the increase of MDA and the decrease of GSH hippocampal levels; (3) markedly improved the cell morphology and alleviated the neuronal loss in hippocampal CA1 and CA3 regions; (4) significantly attenuated the increase of CASP3 and BAX and the decrease of BCL2 hippocampal levels. CONCLUSIONS MB has a protective effect in the SSSE model and may be useful as an adjuvant for preventing or treating epilepsy in humans.
Assuntos
Anticonvulsivantes/uso terapêutico , Complexo Nuclear Basolateral da Amígdala/patologia , Azul de Metileno/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Animais , Anticonvulsivantes/farmacologia , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Caspase 3/metabolismo , Estimulação Elétrica , Eletroencefalografia , Glutationa/metabolismo , Hipocampo/patologia , Masculino , Malondialdeído/metabolismo , Azul de Metileno/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Ratos Wistar , Estado Epiléptico/metabolismo , Estado Epiléptico/patologia , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Uremic Encephalopathy (UE) is a neurological complication associated with acute or chronic renal failure. Imaging findings of UE may present involvement of the basal ganglia, cortical or subcortical regions, and white matter. We report a rare case of UE caused by neurogenic bladder with isolated brainstem involvement revealed by magnetic resonance imaging (MRI). Immediate therapy resulted in full recovery of neurological signs and changes on MRI. CASE PRESENTATION: A 14-year-old Han Chinese woman with a history of chronic renal failure caused by neurogenic bladder. On admission, she was unconscious and her pupils presented different sizes, while her vital signs were normal. MRI showed high signal in the dorsal pontine base and in the mid brain on fluid-attenuated inversion-recovery (FLAIR) imaging and on T2-weighted imaging while the signal was normal on diffusion-weighted images (DWI). Blood analysis revealed renal failure and acidosis. After urinary retention treatment and acidosis correction, the patient soon recovered. Follow-up MRI 2 months after the discharge revealed complete resolution of UE in the brainstem. CONCLUSION: We reported a rare case of a patient with UE that had unusual imaging manifestations for whom timely diagnosis and treatment assured recovery.
Assuntos
Encefalopatias/diagnóstico por imagem , Tronco Encefálico/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Substância BrancaRESUMO
Most antiepileptic drugs (AEDs) interfere with cognitive function, and there is therefore an urgent need for AEDs that are effective but do not have this side effect. Various studies have reported the antiinflammatory and cytoprotective properties of the natural flavonoid luteolin (LU); however, none has examined systematically its antiseizure potential. The current study investigated the effects of LU on pentylenetetrazole (PTZ)-induced cognitive impairment in rats and the underlying mechanisms. Seizures were induced in rats by daily injection of PTZ for 36 days. Two other groups were pretreated with LU (50 or 100 mg/kg/day by oral administration) 30 min prior to PTZ administration. Seizure severity was scored, and cognitive function was tested in the Morris water maze. Neuronal damage, mitochondrial generation of reactive oxygen species, oxidative stress, phosphoactivation of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB) pathway, and brain-derived neurotrophic factor (BDNF) expression were measured in the hippocampus. Pretreatment with LU suppressed seizure induction, duration, and severity following PTZ injection, reversed cognitive impairment, reduced neuronal and oxidative stress damage, and increased phosphoactivation of PKA and CREB as well as BDNF expression. These results indicate that LU should be further investigated as a treatment for epilepsy.
Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Luteolina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Pentilenotetrazol/efeitos adversos , Animais , Anticonvulsivantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva/psicologia , Convulsivantes/toxicidade , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteína A de Ligação a Elemento de Resposta do AMP Cíclico , Epilepsia/tratamento farmacológico , Masculino , Proteínas Quinases/metabolismo , Ratos , Convulsões/induzido quimicamente , Transdução de Sinais/efeitos dos fármacosRESUMO
Epilepsy, especially the medial temporal lobe epilepsy (TLE), can result in cognitive impairment. Lowfrequency repetitive magnetic stimulation (rTMS) has been verified to suppress neural excitability and reduce seizures. Given its potential in modifying cortical activity, we aimed to investigate its impact on cognitive function in the context of epilepsy, a condition where the use of rTMS has not been extensively explored. However, the influence on cognitive function has not yet been investigated. Therefore, this study aimed to investigate the effects of lowfrequency rTMS on cognitive improvement in epileptic rats. Rats used in this study were randomly divided into five groups: the sham group, the epilepsy group, and three epilepsy groups treated with rTMS at different frequencies. Each group underwent the Morris water maze test to investigate hippocampusdependent episodic memory, to evaluate their cognitive performance. Further assessments included patch clamp and western blot techniques to estimate the synaptic function in the hippocampus. Comparison between groups showed that lowfrequency rTMS significantly reduced spontaneous recurrent seizures and improved spatial learning and memory impairment in epileptic rats. Additionally, rTMS remodeled the synaptic plasticity affected by seizures and notably enhanced the expression of AMPAR and synaptophysin. Lowfrequency rTMS can antagonize the cognitive impairment caused by TLE, and promote synaptic connections.
Assuntos
Disfunção Cognitiva , Epilepsia do Lobo Temporal , Animais , Ratos , Epilepsia do Lobo Temporal/terapia , Estimulação Magnética Transcraniana , Cognição , Convulsões , Disfunção Cognitiva/terapiaRESUMO
Invasive surgical cerebrum biopsy results in delayed treatment for the definitive diagnosis of primary central nervous system lymphoma (PCNSL). The existent research was aimed at confirming the underlying diagnostic miRNAs of distinguishing PCNSL from glioma. A publicly available miRNA expression profiles (GSE139031) from adult PCNSL as well as glioma specimens were provided by GEO datasets. Differentially expressed miRNAs (DEMs) were filtered between 42 PCNSL patients and 170 glioma patients. Candidate miRNAs were identified through SVM-RFE analysis and LASSO model. ROC assays were operated to determine the diagnostic value of serum miRNAs in distinguishing PCNSL from glioma. StarBase v2.0 was applied to screen the targeting genes of miRNAs, and KEGG analysis was applied using the targeting genes of miRNAs. In this study, we identified 12 dysregulated miRNAs between PCNSL and glioma samples. The ten critical miRNAs (miR-6820-3p, miR-6803-3p, miR-30a-3p, miR-4751, miR-3918, miR-146a-3p, miR-548am-3p, miR-371a-3p, miR-487a-3p, and miR-4756-5p) between these two algorithms were ultimately identified. The results of KEGG revealed that the targeting genes of hsa-miR-3918 were primarily related to MAPK signal pathway, PI3K-Akt signal pathway, and human papillomavirus infection. Overall, bioinformatics analysis revealed that ten miRNAs are potential biomarker for distinguishing PCNSL from glioma.
Assuntos
Glioma , Linfoma , MicroRNAs , Adulto , Sistema Nervoso Central , Glioma/diagnóstico , Glioma/genética , Humanos , Linfoma/diagnóstico , Linfoma/genética , MicroRNAs/genética , Fosfatidilinositol 3-QuinasesRESUMO
PURPOSE: To evaluate the sealing ability of three different lengths of root canal fillings after post space and two different obturation techniques by using a glucose leakage test, and provide theoretical basis for clinical selection of best collocation of root canal filling methods and residual root canal filling materials. METHODS: One hundred and thirty-two extracted single-root teeth were randomly divided into 6 experimental groups(n=20 each), positive(n=6)and negative controls(n=6). After root canal preparation, different treatments were performed in different groups. Group A: lateral compaction and 4 mm length of root canal fillings after post space. Group B: lateral compaction and 6 mm length of root canal fillings after post space. Group C: lateral compaction and 8 mm length of root canal fillings after post space. Group D: warm gutta vertical compaction and 4 mm length of root canal fillings after post space. Group E: warm gutta vertical compaction and 6 mm length of root canal fillings after post space. Group F: warm gutta vertical compaction and 8 mm length of root canal fillings after post space. Group G: random root canal filling. Group H: no root canal filling. A glucose leakage model was used for quantitative evaluation of the coronal to apical microleakage. SPSS 19.0 software package was used for statistical analysis. RESULTS: Lateral compaction showed significantly more leakage than warm gutta vertical compaction at all observation times, regardless of the length of the root canal fillings. The shorter the length of root canal fillings after post space, the worse the effect of the apical sealing for the same filling method. There was significant difference between 4 mm and 6 mm (P<0.05), but no significant difference between 8 mm and 6 mm (P>0.05). CONCLUSIONS: Warm vertical compaction shows a better sealing result than cold lateral compaction of gutta-percha. The shorter the length of root canal fillings after post space, the worse the effect of the apical sealing. 6 mm may be the proper residual root filling material length after post space preparation.
Assuntos
Cimentos de Resina , Materiais Restauradores do Canal Radicular , Obturação do Canal Radicular , Infiltração Dentária , Cavidade Pulpar , Guta-Percha , Humanos , Distribuição Aleatória , Preparo de Canal RadicularRESUMO
Mild brief hypoxia can protect against neuronal damage induced by epileptic seizures, at least in part by inhibiting apoptosis. Further elucidation of the antiepileptic mechanisms and optimization of the conditioning protocols are required before this strategy can be considered for clinical intervention. In this study, we compared the effects of different hypoxic preconditioning protocols on spontaneous recurrent seizures (SRS), intracellular free calcium concentration ([Ca(2+)]i), and apoptosis rate following pilocarpine-induced status epilepticus (SE). Male Sprague Dawley rats were subjected to either chronic intermittent hypobaric hypoxia (CIHH) or chronic intermittent normobaric hypoxia (CINH) (both for 6h/day × 28 consecutive days) prior to pilocarpine-induced SE. The possible anticonvulsant and neuroprotective effects of CIHH and CINH were compared by video monitoring of behavioral seizure activity (frequency, delay), Nissl staining and Fluoro-Jade B (FJB) staining to examine changes in the morphology of hippocampal pyramidal neurons, and flow cytometry to detect the quantification of [Ca(2+)]i and cell apoptosis. Both hypoxic preconditioning protocols reduced the frequency and severity of SRS, suppressed post-ictal [Ca(2+)]i elevations, and inhibited neuronal apoptosis in the rat hippocampus compared to pilocarpine alone, but CIHH was more effective than CINH. Thus, mild hypoxic pretreatment, particularly when delivered as CIHH, may be a novel strategy for the clinical prevention and treatment of epilepsy.
Assuntos
Hipocampo/patologia , Hipóxia/metabolismo , Precondicionamento Isquêmico , Neurônios/patologia , Convulsões/patologia , Animais , Apoptose , Cálcio/análise , Hipocampo/química , Masculino , Pilocarpina , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamenteRESUMO
Cognitive dysfunction is commonly observed in epileptic patients. It has been shown that not only epilepsy but also antiepileptic drugs could induce cognitive impairment. Thus, there is an urgent need for drugs that can suppress seizures without causing cognitive deficit. Recent studies have shown that oxidative stress is involved in the pathophysiology of epilepsy, and many antioxidants have an antiepileptic property. Epigallocatechin-3-gallate (EGCG), a catechin polyphenols component, is found to be an effective antioxidant. The purpose of this study was to assess the effect of EGCG against seizures, seizure-induced oxidative stress and cognitive impairment in pentylenetetrazole-induced kindling. Male Sprague-Dawley rats were injected intraperitoneally with a dose of 35 mg/kg of pentylenetetrazole (PTZ) once every alternate day for 13 injections. EGCG was administered daily in two doses (25mg/kg and 50mg/kg) intraperitoneally along with alternate-day PTZ. Morris water maze test was carried out 24h after the last injection of PTZ, and the oxidative stress parameters (malondialdehyde and glutathione) were assessed after the completion of the behavioral test. The results showed that EGCG dose-dependently suppressed the progression of kindling. EGCG also ameliorated the cognitive impairment and oxidative stress induced by PTZ kindling. These observations suggest that EGCG may be a potential agent for the treatment of epilepsy as well as a preventive agent against cognitive impairment induced by seizure.
Assuntos
Catequina/análogos & derivados , Cognição/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Convulsões/prevenção & controle , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catequina/farmacologia , Convulsivantes/toxicidade , Excitação Neurológica/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamenteRESUMO
Maternal seizure has adverse effects on brain histology as well as on learning and memory ability in progeny. An enriched environment (EE) is known to promote structural changes in the brain and improve cognitive and motor deficits following a variety of brain injuries. Whether EE treatment in early postnatal periods could restore cognitive impairment induced by prenatal maternal seizure is unknown. Adult female Sprague-Dawley rats were randomly separated into two groups and were injected intraperitoneally either saline or pentylenetetrazol (PTZ) for 30 days. Then the fully kindled rats and control animals were allowed to mate. PTZ administration was continued until delivery, while the control group received saline at the same time. After weaning at postnatal day 22, one-half of the male offspring in the control and in the prenatal maternal group were given the environmental enrichment treatment through all the experiments until they were tested. Morris water maze testing was performed at 8 weeks of age. Western blot and synaptic ultrastructure analysis were then performed. We found that EE treatment reversed spatial learning deficits induced by prenatal maternal seizure. An EE also reversed the changes in synaptic ultrastructure following prenatal maternal seizure. In addition, prenatal maternal seizure significantly decreased phosphorylation states of cAMP response element binding (CREB) in the hippocampus, whereas EE reversed this reduced expression. These findings suggest that EE treatment on early postnatal periods could be a potential therapy for improving cognitive deficits induced by prenatal maternal seizure.