Asunto(s)
Estimulación Encefálica Profunda , Mucolipidosis , Mioclonía , Humanos , Mioclonía/terapiaRESUMEN
OBJECTIVES: Deep brain stimulation (DBS) for Parkinson's disease (PD) has been applied to clinic for approximately 30 years. The goal of this review is to explore the similarities and differences between "awake" and "asleep" DBS techniques. METHODS: A comprehensive literature review was carried out to identify relevant studies and review articles describing applications of "awake" or "asleep" DBS for Parkinson's disease. The surgical procedures, clinical outcomes, costs and complications of each technique were compared in detail through literature review. RESULTS: The surgical procedures of awake and asleep DBS surgeries rely upon different methods for verification of intended target acquisition. The existing research results demonstrated that the stereotactic targeting accuracy of lead placement obtained by either method is reliable. There were no significant differences in clinical outcomes, costs, or complications between the two techniques. CONCLUSION: The surgical and clinical outcomes of asleep DBS for PD are comparable to those of awake DBS.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Resultado del Tratamiento , Anestesia General , Anestesia Local , Humanos , Inconsciencia , VigiliaRESUMEN
Previous studies demonstrated that Nav1.5 splice variants, including Nav1.5a and Nav1.5c, were expressed in dorsal root ganglia (DRG) neurons. However, since nine Nav1.5 isoforms have been identified, whether other Nav1.5 splice variants, especially the neonatal Nav1.5 splice variant, express in the DRG neurons is still unknown. In this study, we systematically investigated the expression of adult and neonatal Nav1.5 isoforms in the DRG neurons and axon of peripheral sensory neurons of rats with spared nerve injury (SNI) by RT-PCR, DNA sequencing, restriction enzyme digestion, immunohistochemistry and immunofluorescence methods. The results demonstrated that both adult and neonatal Nav1.5 isoforms were expressed in the DRG neurons, but their expression ratio was ~2.5:1. In SNI rat models, the expression of both adult and neonatal Nav1.5 decreased by approximately a half in both mRNA and protein levels. In contrast, the expression of protein kinase C (PKC)-γ, one of the negative modulators for sodium currents, increased by ~1-fold. Taken together, this study first confirmed the expression of both adult and neonatal Nav1.5 isoforms in the DRG neurons and axon of peripheral sensory neurons of rat, but their expression level decreased in pain models. The upregulation of PKC-γ may directly or indirectly downregulate the expression of Nav1.5 isoforms in SNI rat models, which may further involve in the pathological process of neuropathic pain.
Asunto(s)
Axones/patología , Regulación hacia Abajo , Ganglios Espinales/patología , Canal de Sodio Activado por Voltaje NAV1.5/genética , Neuralgia/genética , Células Receptoras Sensoriales/patología , Animales , Axones/metabolismo , Modelos Animales de Enfermedad , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Masculino , Canal de Sodio Activado por Voltaje NAV1.5/análisis , Neuralgia/patología , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas Sprague-Dawley , Células Receptoras Sensoriales/citología , Células Receptoras Sensoriales/metabolismoRESUMEN
Voltage-gated sodium channels serve an essential role in the initiation and propagation of action potentials for central neurons. Previous studies have demonstrated that two novel variants of Nav1.5, designated Nav1.5e and Nav1.5f, were expressed in the human brain cortex. To date, nine distinct sodium channel isoforms of Nav1.5 have been identified. In the present study, the expression of Nav1.5 splice variants in the frontal lobe of the human brain cortex was systematically investigated. The results demonstrated that wild Nav1.5 and its splice variants, Nav1.5c and Nav1.5e, were expressed in the frontal lobe of the human brain cortex. Nav1.5a, Nav1.5b and Nav1.5d splice variants were not detected. However, the expression level of different Nav1.5 variants was revealed to vary. The expression ratio of wild Nav1.5 vs. Nav1.5c and Nav1.5e was approximately 5:1 and 1:5, respectively. Immunochemistry results revealed that Nav1.5 immunoreactivity was predominantly in neuronal cell bodies and processes, including axons and dendrites, whereas little immunoreactivity was detected in the glial components. These results revealed that a minimum of four Nav1.5 splice variants are expressed in the frontal lobe of the human brain cortex. This indicates that the previously reported tetrodotoxinresistant sodium current was a compound product of different Nav1.5 variants. The present study revealed that Nav1.5 channels have a more abundant expression in the human brain than previously considered. It also provided further insight into the complexity and functional significance of Nav1.5 channels in human brain neurons.
Asunto(s)
Sistema Nervioso Central/metabolismo , Lóbulo Frontal/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5/genética , Isoformas de Proteínas/genética , Adulto , Anciano , Empalme Alternativo/genética , Axones/metabolismo , Femenino , Lóbulo Frontal/cirugía , Regulación de la Expresión Génica/genética , Humanos , Masculino , Potenciales de la Membrana/genética , Persona de Mediana Edad , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Neuronas/metabolismo , Técnicas de Placa-Clamp , Isoformas de Proteínas/metabolismoRESUMEN
Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.
Asunto(s)
Neuronas/metabolismo , Canales de Sodio Activados por Voltaje/metabolismo , Animales , HumanosRESUMEN
It has previously been demonstrated that there are various voltage gated sodium channel (Nav) 1.5 splice variants expressed in brain tissue. A total of nine Nav1.5 isoforms have been identified, however, the potential presence of further Nav1.5 variants expressed in brain neurons remains to be elucidated. The present study systematically investigated the expression of various Nav1.5 splice variants and their associated electrophysiological properties in the rat brain tissue, via biochemical analyses and wholecell patch clamp recording. The results demonstrated that adult Nav1.5 was expressed in the rat, in addition to the neonatal Nav1.5, Nav1.5a and Nav1.5f isoforms. Further studies indicated that the expression level ratio of neonatal Nav1.5 compared with adult Nav1.5 decreased from 1:1 to 1:3 with age development from postnatal (P) day 0 to 90. This differed from the ratios observed in the developing rat hearts, in which the expression level ratio decreased from 1:4 to 1:19 from P0 to 90. The immunohistochemistry results revealed that Nav1.5 immunoreactivity was predominantly observed in neuronal cell bodies and processes, whereas decreased immunoreactivity was detected in the glial components. Electrophysiological analysis of Nav1.5 in the rat brain slices revealed that an Na current was detected in the presence of 300 nM tetrodotoxin (TTX), however this was inhibited by ~1 µM TTX. The TTXresistant Na current was activated at 40 mV and reached the maximum amplitude at 0 mV. The results of the present study demonstrated that neonatal and adult Nav1.5 were expressed in the rat brain and electrophysiological analysis further confirmed the functional expression of Nav1.5 in brain neurons.
Asunto(s)
Encéfalo/metabolismo , Regulación de la Expresión Génica , Miocardio/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5/genética , Empalme Alternativo , Animales , Secuencia de Bases , Fenómenos Electrofisiológicos , Inmunohistoquímica , Masculino , Familia de Multigenes , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Especificidad de Órganos/genética , Isoformas de Proteínas , RatasRESUMEN
AIM: To explore the treatment efficacy of microsurgery for secondary epilepsy from hippocampal lesions. MATERIAL AND METHODS: The clinical data, pathological findings, surgical methods and surgical outcomes of 56 patients with secondary epilepsy from hippocampal lesions were retrospectively analyzed. RESULTS: Postoperative pathological examinations confirmed that 27 patients had gliomas, 17 patients had vascular malformations and 12 patients had hippocampal sclerosis. Twenty-nine patients underwent selective resection of the lesioned tissue and the surrounding infiltrated tissue, and 26 patients underwent a more generous removal of the anterior temporal lobe, lesioned tissue, infiltrated tissue and medial structures of the temporal lobe. Fifty patients were followed up with an average follow-up duration of 25.5 months. At postoperative one year, the remission rate of epilepsy that achieved Engel grade I was 80.8% (21/26) and 83.3% (20/24) for the selective resection and more generous resection, respectively, indicating that the difference between the two methods was insignificant. CONCLUSION: Microsurgery is the first choice for the treatment of secondary epilepsy from hippocampal lesions. Various operative routes and methods can be selected based on the lesion natures. Long-term favorable outcome of seizure control following microsurgery can be achieved in most of the patients.
Asunto(s)
Lobectomía Temporal Anterior/métodos , Neoplasias Encefálicas/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Glioma/complicaciones , Hipocampo/cirugía , Microcirugia/métodos , Convulsiones/cirugía , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Malformaciones Vasculares del Sistema Nervioso Central/patología , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Femenino , Glioma/patología , Glioma/cirugía , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Esclerosis/complicaciones , Esclerosis/patología , Esclerosis/cirugía , Convulsiones/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
Malignant peripheral nerve sheath tumors of the scalp are rare lesions of the nervous system. Only 14 cases have been reported to date. The field of neurosurgery has struggled with diagnosing and treating these tumors. In this report, we present two cases of giant malignant peripheral nerve sheath tumors of the scalp and retrospectively analyze the clinical features, imaging findings, pathological features, and prognoses of these two patients. Each underwent microsurgery and radiotherapy. In addition, based on a literature review, we discuss the diagnostic and therapeutic strategies used to treat these unusual lesions.
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Neurilemoma/cirugía , Cuero Cabelludo/cirugía , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neurilemoma/patología , Procedimientos Neuroquirúrgicos , Pronóstico , Estudios Retrospectivos , Literatura de Revisión como Asunto , Cuero Cabelludo/patología , Tomografía Computarizada por Rayos XRESUMEN
The α-subunit of tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel (VSGC, Nav1.5/SCN5A) has been found from the rat heart and human neuroblastoma cell line NB-1, but its expression in rat brain has not been identified radically. In this study, a reverse transcriptase-polymerase chain reaction was used to clone the full sequence of Nav1.5 (designated as rN1) α-subunit in rat brain and compared the distribution in different lobe of brain in different developmental stages. The open reading frame of rN1 encodes 2,016 amino acid residues and sequence analysis indicated that rN1 is highly homologous with 96.53% amino acids identity to rat cardiac Nav1.5 (rH1) and 96.13% amino acids identity to human neuroblastoma Nav1.5 (hNbR1). It has all the structural features of a VSGC and the presence of a cysteine residue (C373) in the pore loop region of domain I suggests that this channel is resistant to TTX. A new exon (exon6A) that is distinct from rH1 was found in DI-S3-S4, meanwhile an isomer of alternative splicing that deleted 53 amino acids (exon18) was found for the first time in domain DII-III in rN1. (designated as rN1-2). Distribution results demonstrated that rN1 expressed discrepancy in different ages and lobe in brain. The expression level of rN1 was gradually more stable in adult than in neonatal; these results suggest that rN1 has a newly identified exon for alternative splicing that is differentfrom rat heart and is more widely expressed in rat brain than previously thought.
Asunto(s)
Tronco Encefálico/metabolismo , Cerebro/metabolismo , Hipocampo/metabolismo , Subunidades de Proteína/genética , Canales de Sodio/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Tronco Encefálico/crecimiento & desarrollo , Cerebro/crecimiento & desarrollo , Clonación Molecular , Regulación del Desarrollo de la Expresión Génica , Hipocampo/crecimiento & desarrollo , Hígado/metabolismo , Masculino , Datos de Secuencia Molecular , Miocardio/metabolismo , Canal de Sodio Activado por Voltaje NAV1.5 , Especificidad de Órganos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades de Proteína/metabolismo , Ratas , Ratas Wistar , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Canales de Sodio/metabolismoRESUMEN
OBJECTIVE: Microsurgery is an optional way to treat parenchymal neurocysticercosis. The aim of this study is to evaluate the therapeutic efficacy of microsurgery in cerebral parenchymal cysticercosis. MATERIALS AND METHODS: A retrospective analysis was performed of the clinical data and outcomes of microsurgery in 20 cases of cerebral parenchymal cysticercosis. RESULTS: All head segments found in cysticercus cysts were removed completely. Total resection of the cystic wall was achieved in 16 cases and subtotal resection in 4 cases. Twelve patients recovered from intracranial hypertension soon after the operation. No novel complications or deaths occurred postoperatively. The patients were followed up for 3 months to 10 years; among them, 14 patients who had epilepsy before surgery were markedly improved and controlled, 4 of 5 patients recovered from hemiparesis within 6 months after surgery, and 2 patients with cerebellar ataxia showed improvement. Two patients were lost to follow-up. CONCLUSIONS: Despite a high rate of misdiagnosis of cerebral parenchymal cysticercosis, microsurgery is associated with satisfactory clinical outcomes in appropriately selected patients.
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Microcirugia/métodos , Neurocisticercosis/cirugía , Procedimientos Neuroquirúrgicos/métodos , Adolescente , Adulto , Anciano , Animales , Anticonvulsivantes/uso terapéutico , Niño , Craneotomía , Cysticercus , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipertensión Intracraneal/etiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurocisticercosis/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Dumbbell C1 and C2 schwannomas are rare and have a distinctive presentation and anatomical features. To study the clinical characteristics of these tumors, we reviewed the microsurgical management of 18 patients with dumbbell C1 and C2 schwannomas by the far lateral approach. Data regarding clinical manifestations, radiological findings and surgical results were analyzed retrospectively. Total and subtotal resection of the tumor was achieved in 15 and three patients, respectively. At the time of discharge, 12 patients showed improvement while five patients remained the same. The average follow-up duration was 43 months (range = 3-110 months); six of seven patients had recovery from local pain or numbness. With the exception of one patient with hemiplegia or hemiparesthesia preoperatively, all patients recovered within 6 months postoperatively. The far lateral approach offers adequate exposure and access with minimal neural manipulation for treating dumbbell C1 and C2 schwannomas, and is considered the preferred surgical approach for resection of these tumors located ventrally or ventrolaterally to the first two cervical vertebrae.
Asunto(s)
Vértebra Cervical Axis/cirugía , Atlas Cervical/cirugía , Microcirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Neoplasias del Sistema Nervioso Periférico/cirugía , Raíces Nerviosas Espinales/cirugía , Adulto , Anciano , Vértebra Cervical Axis/patología , Atlas Cervical/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Periférico/patología , Estudios Retrospectivos , Raíces Nerviosas Espinales/patología , Adulto JovenRESUMEN
Na+ currents with tetrodotoxin resistance (TTX-R) have been observed in neurons, but the full-length cDNAs encoding the TTX-R Nav1.5 channels in human and rat brains have not been identified. In this study, four full-length cDNAs encoding the alpha-subunits of the Nav1.5 channels in human and rat cerebral cortexes were cloned and designated hB1, hB2, rN1 and rN2 (accession number: EF629346, EF629347, EF618549, EF618550). The longest open reading frame of hB1 or rN1 encodes 2016 amino acid residues. Sequence analysis has indicated that hB1 is highly homologus with human cardiac Nav1.5/SCN5A (hH1) with >98% amino acid identity. Genomic sequence analysis of Nav1.5/SCN5A revealed that it is exon6A rather than exon6 splice variant of Nav1.5 which is expressed in human and rat brains. Alternative splicing variants hB2 and rN2, which lack exon24 and encode proteins of 1998 amino acids, were also identified. Furthermore, the total Nav1.5 mRNA and Navbeta1 mRNA were detected in 16 different tissue types of developing Wistar rats by reverse polymerase chain reaction (RT-PCR), and their expression patterns varied among different tissue types with age development. These results suggest that Nav1.5 channels in human and rat brains are encoded by new variants of Nav1.5/SCN5A and Nav1.5 is more widely distributed and expressed than previously thought.
Asunto(s)
Encéfalo/metabolismo , Proteínas Musculares/química , Proteínas Musculares/genética , ARN Mensajero/genética , Canales de Sodio/química , Canales de Sodio/genética , Envejecimiento/genética , Envejecimiento/metabolismo , Empalme Alternativo/genética , Animales , Animales Recién Nacidos , Clonación Molecular/métodos , ADN Complementario/análisis , ADN Complementario/genética , Exones/genética , Humanos , Masculino , Datos de Secuencia Molecular , Canal de Sodio Activado por Voltaje NAV1.5 , Sistemas de Lectura Abierta/genética , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Subunidades de Proteína/química , Subunidades de Proteína/genética , ARN Mensajero/análisis , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Especificidad de la EspecieRESUMEN
Exon6A of Nav1.5/SCN5A was first found in the cloning of Nav1.5 from the human neuroblastoma cell line NB-1 (Ou et al., 2005), but its expression in brain and non-brain tissue had not been identified. In this study, we have further investigated this new exon and compared it with exon6 of Nav1.5/SCN5A. Reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis both confirmed that it is exon6A that encodes Nav1.5 in brain tissue, and it is exon6 that encodes Nav1.5 in non-brain tissue. The expression of exon6A in different parts of the brain is different, with expression levels in the order of hippocampus > cerebral cortex > brain stem > cerebellum. Different expression levels of exon6 in different tissues of Wistar rats were also found. These results suggest that exon6A is unique in encoding the Nav1.5 channels in the central nervous system. In addition, novel alternative splicing of Nav1.5/SCN5A, lacking exon24, was first found in our study. This alternative splicing was also found in other tissues, such as heart, lung and testis. However, the ratio of the two variants changed differently in different types of tissues in developing rats. These results suggest that Nav1.5/SCN5A has a newly identified alternative splicing, and the Nav1.5 channels in the brain are encoded by new variants of Nav1.5/SCN5A.
Asunto(s)
Encéfalo/metabolismo , Proteínas del Tejido Nervioso/genética , Canales de Sodio/genética , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Exones/genética , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Corazón/crecimiento & desarrollo , Humanos , Datos de Secuencia Molecular , Miocardio/metabolismo , Canal de Sodio Activado por Voltaje NAV1.1 , Proteínas del Tejido Nervioso/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Canales de Sodio/metabolismoAsunto(s)
Traumatismos Craneocerebrales/complicaciones , Apoplejia Hipofisaria/etiología , Neoplasias Hipofisarias/complicaciones , Hemorragia Subaracnoidea/etiología , Anciano , Humanos , Imagen por Resonancia Magnética , Masculino , Apoplejia Hipofisaria/complicaciones , Neoplasias Hipofisarias/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Both tetrodotoxin-sensitive (TTX-S) and TTX-resistant (TTX-R) voltage-dependent Na+ channels are expressed in the human neuroblastoma cell line NB-1, but a gene encoding the TTX-R Na+ channel has not been identified. In this study, we have cloned cDNA encoding the alpha subunit of the TTX-R Na+ channel in NB-1 cells and designated it hNbR1. The longest open reading frame of hNbR1 (accession no. AB158469) encodes 2016 amino acid residues. Sequence analysis has indicated that hNbR1 is highly homologous with human cardiac Nav1.5/SCN5A with > 99% amino acid identity. The presence of a cysteine residue (Cys373) in the pore-loop region of domain I is consistent with the supposition that hNbR1 is resistant to TTX. Analysis of the genomic sequence of SCN5A revealed a new exon encoding S3 and S4 of domain I (exon 6A). In addition, an alternative splicing variant, lacking exon 18, that encodes 54 amino acids in the intracellular loop between domains II and III was found (hNbR1-2; accession no. AB158470). Na+ currents in human embryonic kidney cells (HEK293) transfected with hNbR1 or hNbR1-2 showed electrophysiological properties similar to those for TTX-R I(Na) in NB-1 cells. The IC50 for the TTX block was approximately 8 microM in both variants. These results suggest that SCN5A has a newly identified exon for alternative splicing and is more widely expressed than previously thought.