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1.
Asian J Psychiatr ; 83: 103541, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36958138

RESUMO

Stereotactic neurosurgery has been employed in autism spectrum disorders (ASD). However, its safety and effectiveness remain unclear owing to limited sample size and other methodological limitations. We aimed to systematically investigate the safety and efficacy of stereotactic neurosurgery for ASD. Eleven studies with 36 patients were included. Stereotactic neurosurgery alleviated the obsessive-compulsive disorder and aggressive behavior symptoms in ASD, with a mean improvement of 42.74% and 59.59% in the Yale-Brown Obsessive Compulsive Scale and Overt Aggression Scale scores, respectively. Systematic studies are necessary to explore the role of deep brain stimulation for social and communication difficulties in ASD.


Assuntos
Transtorno do Espectro Autista , Estimulação Encefálica Profunda , Neurocirurgia , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno do Espectro Autista/cirurgia , Transtorno do Espectro Autista/diagnóstico , Transtorno Obsessivo-Compulsivo/cirurgia , Transtorno Obsessivo-Compulsivo/diagnóstico , Agressão
2.
J Neuroimmunol ; 298: 153-9, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27609289

RESUMO

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsies in adults and proinflammatory cytokines have long been thought to play an important role in pathogenesis and epileptogenicity. In the present study, we investigated the levels and expression patterns of the interleukin 17 (IL-17) system in temporal neocortex and hippocampus from 24 patients with MTLE and 8 control (Ctr) samples. We found that IL-17 and IL-17 receptor (IL-17R) were clearly upregulated in MTLE at both mRNA and protein levels, compared with Ctr. Immunostaining indicated that neurons, astrocytes, microglia and endothelial cells of blood vessels are the major sources of IL-17. These findings suggest that IL-17 system may be involved in the pathogenesis and epileptogenicity of MTLE.


Assuntos
Córtex Cerebral/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/metabolismo , Interleucina-17/metabolismo , Receptores de Interleucina-7/metabolismo , Adolescente , Adulto , Análise de Variância , Contagem de Células , Epilepsia do Lobo Temporal/metabolismo , Feminino , Humanos , Interleucina-17/genética , Masculino , RNA Mensageiro/metabolismo , Receptores de Interleucina-7/genética , Adulto Jovem
3.
J Neuroinflammation ; 13(1): 85, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27095555

RESUMO

BACKGROUND: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children. Accumulating evidence suggests that activation of the microglia/macrophage and concomitant inflammatory response in FCD IIb and TSC may contribute to the initiation and recurrence of seizures. The membrane glycoproteins CD47 and CD200, which are highly expressed in neurons and other cells, mediate inhibitory signals through their receptors, signal regulatory protein α (SIRP-α) and CD200R, respectively, in microglia/macrophages. We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro. The level of interleukin-4 (IL-4), a modulator of CD200, was also investigated. METHODS: Twelve FCD IIb (range 1.8-9.5 years), 13 TSC (range 1.5-10 years) patients, and 6 control cases (range 1.5-11 years) were enrolled. The levels of CD47/SIRP-α and CD200/CD200R were assessed by quantitative real-time polymerase chain reaction and western blot. The expression pattern of CD47/SIRP-α and CD200/CD200R was investigated by immunohistochemical analysis, and the cytokine concentrations were measured by enzyme-linked immune-sorbent assays. RESULTS: Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed. CD47, SIRP-α, and CD200 were decreasingly expressed in dysmorphic neuron, balloon cells, and giant cells. CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1ß or IL-17 production. CONCLUSIONS: Our results suggest that microglial activation may be partially caused by CD47/SIRP-α- and CD200/CD200R-mediated reductions in the immune inhibitory pathways within FCD IIb and TSC cortical lesions where chronic neuroinflammation has been established. Upregulation or activation of CD47/SIRP-α and CD200/CD200R may have therapeutic potential for controlling neuroinflammation in human FCD IIb and TSC.


Assuntos
Antígenos CD/biossíntese , Encéfalo/metabolismo , Antígeno CD47/biossíntese , Epilepsia/metabolismo , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , Esclerose Tuberosa/metabolismo , Western Blotting , Criança , Pré-Escolar , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Microglia/metabolismo , Neurônios/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
4.
J Mol Neurosci ; 59(2): 241-50, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26798047

RESUMO

Mesial temporal lobe epilepsy (MTLE) is a frequent form of focal intractable epilepsy in adults. We previously reported overexpression of vascular endothelial growth factor C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, in epilepsy-associated tuberous sclerosis complex. To identify whether VEGF-C and its receptors are involved in epileptogenesis of MTLE, we investigated the levels and expression pattern of VEGF-C and its receptors in temporal neocortex and hippocampus (HPC) from 28 patients with MTLE and ten control (CTX) subjects. Real-time quantitative polymerase chain reaction and Western blotting results revealed upregulated mRNA and immunoreactive protein levels of VEGF-C, VEGFR-2, and VEGFR-3 in the MTLE group compared to the control groups. Immunohistochemistry and double-labeled immunofluorescence showed that VEGF-C was highly expressed in neurons and astrocytes, including reactive astrocytes and vascular endothelial cells, VEGFR-2 was expressed at a high level in reactive astrocytes and vascular endothelial cells, but not in neurons, whereas VEGFR-3 was only overexpressed in reactive astrocytes. Taken together, these findings suggest that VEGF-C and its receptors, VEGFR-2 and VEGFR-3, may contribute to the epileptogenesis of MTLE.


Assuntos
Epilepsia do Lobo Temporal/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Astrócitos/metabolismo , Estudos de Casos e Controles , Epilepsia do Lobo Temporal/genética , Feminino , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Masculino , Neocórtex/citologia , Neocórtex/metabolismo , Neurônios/metabolismo , Fator C de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética
5.
PLoS One ; 9(7): e101668, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24991814

RESUMO

Salvianolic acid B (SalB), a bioactive compound isolated from the plant-derived medicinal herb Danshen, has been shown to exert various anti-oxidative and anti-inflammatory activities in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of SalB in Parkinson's disease (PD) models. To determine the neuroprotective effects of SalB in vitro, MPP+- or lipopolysaccharide (LPS)-induced neuronal injury was achieved using primary cultures with different compositions of neurons, microglia and astrocytes. Our results showed that SalB reduced both LPS- and MPP+-induced toxicity of dopamine neurons in a dose-dependent manner. Additionally, SalB treatment inhibited the release of microglial pro-inflammatory cytokines and resulted in an increase in the expression and release of glial cell line-derived neurotrophic factor (GDNF) from astrocytes. Western blot analysis illustrated that SalB increased the expression and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The knockdown of Nrf2 using specific small interfering RNA (siRNA) partially reversed the SalB-induced GDNF expression and anti-inflammatory activity. Moreover, SalB treatment significantly attenuated dopaminergic (DA) neuronal loss, inhibited neuroinflammation, increased GDNF expression and improved the neurological function in MPTP-treated mice. Collectively, these findings demonstrated that SalB protects DA neurons by an Nrf-2 -mediated dual action: reducing microglia activation-mediated neuroinflammation and inducing astrocyte activation-dependent GDNF expression. Importantly the present study also highlights critical roles of glial cells as targets for developing new strategies to alter the progression of neurodegenerative disorders.


Assuntos
Astrócitos/efeitos dos fármacos , Benzofuranos/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Doença de Parkinson/tratamento farmacológico , 1-Metil-4-fenilpiridínio/toxicidade , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/metabolismo , Modelos Biológicos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia
6.
J Mol Neurosci ; 53(2): 176-82, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24682892

RESUMO

Focal cortical dysplasia (FCD) represents a well-recognized cause of medically intractable epilepsy. Previous studies have indicated that seizures can reduce brain pH and then eliminate seizure discharges. Acid-sensing ion channels (ASICs) are H(+)-gated cation channels that are widely expressed in the central and peripheral nervous systems. To understand the potential roles of ASIC1a in the epileptogenesis of FCD, we investigated the expression and distribution patterns of ASIC1a in surgical specimens from patients with FCD and age-matched normal cortices (CTX). Decreased ASIC1a messenger RNA (mRNA) and protein expression were detected in FCD compared with CTX. Moreover, the expression of ASIC1a was significantly lower in FCD type II than FCD type I. Immunohistochemistry results indicated that the overall immunoreactivity of the ASIC1a staining was diminished in the dysplastic cortices of FCD compared to the CTX samples. In FCD, ASIC1a immunoreactivity was mainly observed in reactive astrocytes and a minority of malformed cells, including hypertrophic neurons, dysmorphic neurons, and balloon cells. Confocal analysis demonstrated that most malformed cells expressing ASIC1a were co-labeled with neuronal rather than astrocytic markers, indicating a neuronal lineage. In conclusion, the downregulation and altered cellular distribution of ASIC1a in FCD suggest that ASIC1a may potentially contribute to the epileptogenesis of FCD.


Assuntos
Canais Iônicos Sensíveis a Ácido/genética , Regulação para Baixo , Malformações do Desenvolvimento Cortical do Grupo I/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Epilepsia , Feminino , Humanos , Lactente , Masculino , Malformações do Desenvolvimento Cortical do Grupo I/diagnóstico , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
J Neuroimmunol ; 262(1-2): 85-91, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23906968

RESUMO

The role of interleukin 17 (IL-17) to epilepsy-associated cortical tubers of tuberous sclerosis complex (TSC) is unknown. We investigated the expression patterns of the IL-17 and IL-17 receptor (IL-17R) in cortical tubers of TSC compared with normal control cortex (CTX). We found that IL-17 and IL-17R were clearly upregulated in cortical tubers at the protein levels. Immunostaining indicated that IL-17 was specifically distributed in the innate immunity cells (DNs, GCs, astrocytes, and microglia) and adaptive immunity cells (T-lymphocytes) as well as the endothelial cells of blood vessels. The overexpression and distribution patterns of IL-17 may be involved in the epileptogenicity of cortical tubers in TSC.


Assuntos
Córtex Cerebral/imunologia , Interleucina-17/genética , Esclerose Tuberosa/imunologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Criança , Pré-Escolar , Epilepsia/etiologia , Epilepsia/imunologia , Epilepsia/patologia , Feminino , Humanos , Lactente , Interleucina-17/biossíntese , Masculino , Receptores de Interleucina-17/biossíntese , Receptores de Interleucina-17/genética , Esclerose Tuberosa/complicações , Esclerose Tuberosa/patologia
8.
J Neuropathol Exp Neurol ; 72(2): 152-63, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23334598

RESUMO

Focal cortical dysplasias (FCDs) are increasingly recognized as important causes of medically intractable epilepsy. To understand the potential role of the interleukin 17 (IL-17) system in the epileptogenesis of FCDs, we studied the expression patterns of the IL-17 system in 15 FCD type Ia (FCDIa), 12 FCD type IIa (FCDIIa), and 12 FCD type IIb (FCDIIb) cortical lesions and compared the results with those in cerebral cortex from 10 control patients. Protein levels of IL-17, IL-17 receptor (IL-17R), and downstream factors of the IL-17 pathway (nuclear factor-κB activator 1 [NFκB; ACT1] and NFκB-p65) were markedly elevated in FCDIa, FCDIIa, and FCDIIb. Moreover, protein levels of IL-17 and IL-17R positively correlated with the frequency of seizures in FCD patients. Immunostaining indicated that IL-17 and IL-17R are highly expressed in neuronal microcolumns, dysmorphic neurons, balloon cells, astrocytes, and vascular endothelial cells. Nuclear factor-κB activator 1 and NFκB-p65 were diffusely expressed in FCDs. In addition, we detected a few IL-17-positive, CD4-positive T lymphocytes in FCDIIa and FCDIIb but not in FCDIa. Taken together, these findings suggest that the overexpression of the IL-17 system and the activation of the IL-17 signal transduction pathway may be involved in the epileptogenicity of cortical lesions in FCDs, thus representing a novel potential target for antiepileptic therapy.


Assuntos
Córtex Cerebral/metabolismo , Interleucina-17/metabolismo , Malformações do Desenvolvimento Cortical/patologia , Receptores de Interleucina-17/metabolismo , Transdução de Sinais/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Contagem de Células , Córtex Cerebral/patologia , Criança , Pré-Escolar , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Lactente , Estudos Longitudinais , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/cirurgia , NF-kappa B/metabolismo , Proteínas de Neurofilamentos/metabolismo , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto Jovem
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