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BACKGROUND: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear. METHODS: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis. RESULTS: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-ß level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. CONCLUSIONS: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.
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Encefalite , Epilepsia do Lobo Temporal , Vírus , Encéfalo/metabolismo , Encefalite/patologia , Epilepsia do Lobo Temporal/patologia , Humanos , Interferon beta , Vírus/metabolismoRESUMO
Epilepsy with comorbid depression has recently attracted increasing attention. Temporal lobe epilepsy (TLE) may represent an increased risk of developing depression, especially if the seizures do not generalize. The two-pore domain potassium channel-TWIK-related K+ channel (TREK-1) plays important roles in both epilepsy and depression. However, the changes in its expression in patients with epilepsy with comorbid depression remain unclear. In the present study, we analyzed depressive symptoms using neuropsychiatric scales in forty-two patients with drug-resistant TLE, who also underwent EEG in waking and sleeping states, as well as 3.0 T brain MRI. We tested for TREK-1 positive neurons and microglial cells in the anterior hippocampi of patients with drug-resistant TLE with and without comorbid depression (n=5/group). Approximately 31% of patients with TLE had comorbid depression (13/42). Meanwhile, the patients who had hippocampal sclerosis had much higher scores on the depression rating scale. The results indicated the contribution of hippocampal sclerosis to the development of depression. Immunostaining of TREK-1 channels was observed in neurons and glia in the anterior hippocampus. Increased immunoreactivity of TREK-1 neurons was observed in the hippocampi of patients with TLE with comorbid depression compared with nondepressed patients with TLE. TREK-1 was expressed in almost all microglia. Curiously, more activated TREK-1-positive microglia were observed in patients with TLE with depression than in those without depression. The results suggested that a change in TREK-1 immunoreactivity was involved, at least partly, in the development of depression as a comorbidity of TLE. Imbalance of the TREK-1 channel may be a potential target for the treatment of patients with epilepsy with comorbid depression.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Depressão/epidemiologia , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/epidemiologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/epidemiologia , Hipocampo , Humanos , NeurôniosRESUMO
OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68â¯%) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63â¯%) patients; seven (37â¯%) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.
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Epilepsia Resistente a Medicamentos , Hemisferectomia , Humanos , Epilepsia Resistente a Medicamentos/cirurgia , Masculino , Feminino , Hemisferectomia/métodos , Estudos Retrospectivos , Criança , Adolescente , Resultado do Tratamento , Adulto , Pré-Escolar , Adulto Jovem , Estudos de Coortes , SeguimentosRESUMO
BACKGROUND: Healthcare workers (HCWs) are at increased risk of contracting coronavirus disease 2019 (COVID-19) as well as worsening mental health problems and insomnia. These problems can persist for a long period, even after the pandemic. However, less is known about this topic. AIM: To analyze mental health, insomnia problems, and their influencing factors in HCWs after the COVID-19 pandemic. METHODS: This multicenter cross-sectional, hospital-based study was conducted from June 1, 2023 to June 30, 2023, which was a half-year after the end of the COVID-19 emergency. Region-stratified population-based cluster sampling was applied at the provincial level for Chinese HCWs. Symptoms such as anxiety, depression, and insomnia were evaluated by the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index. Factors influencing the symptoms were identified by multivariable logistic regression. RESULTS: A total of 2000 participants were invited, for a response rate of 70.6%. A total of 1412 HCWs [618 (43.8%) doctors, 583 (41.3%) nurses and 211 (14.9%) nonfrontline], 254 (18.0%), 231 (16.4%), and 289 (20.5%) had symptoms of anxiety, depression, and insomnia, respectively; severe symptoms were found in 58 (4.1%), 49 (3.5%), and 111 (7.9%) of the participants. Nurses, female sex, and hospitalization for COVID-19 were risk factors for anxiety, depression, and insomnia symptoms; moreover, death from family or friends was a risk factor for insomnia symptoms. During the COVID-19 outbreak, most [1086 (76.9%)] of the participating HCWs received psychological interventions, while nearly all [994 (70.4%)] of them had received public psychological education. Only 102 (7.2%) of the HCWs received individual counseling from COVID-19. CONCLUSION: Although the mental health and sleep problems of HCWs were relieved after the COVID-19 pandemic, they still faced challenges and greater risks than did the general population. Identifying risk factors would help in providing targeted interventions. In addition, although a major proportion of HCWs have received public psychological education, individual interventions are still insufficient.
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Objective: The aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated gangliogliomas (GG) with CD34 expression and BRAFV600E mutation. Methods: Clinical data of patients who underwent epilepsy surgery for GG were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAFV600E mutation in GG. Results: A total of 208 patients with GG had immunohistochemical detection of CD34 expression (positive/negative: 184/24), and among them, 89 patients had immunohistochemical detection of BRAFV600E mutation (positive/negative: 54/35). By univariate and multivariate analyses, seizure aura (p = 0.025), concordance of ictal electroencephalogram (EEG) findings (p = 0.045) and medial temporal tumor (p = 0.030) were found to be related to CD34 expression, but only hospitalization time (p = 0.042) was different for BRAF-mutated status. In addition, drug-resistant epilepsy (p = 0.040) and concordance of interictal EEG findings (p = 0.009) were found to be associated with tumor progression-free survival (PFS) in univariate analysis, but only concordance of interictal EEG findings was with significance in multivariate analysis. However, CD34 expression or BRAFV600E mutation in GG was not found to be associated with surgical outcomes of seizure control and tumor PFS. Conclusion: The CD34 expression or BRAFV600E mutation in GG may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence.
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As a common and serious psychiatric disorder, depression significantly affects psychosocial functioning and quality of life. However, the mechanism of depression is still enigmatic and perplexing, which limits its precise and effective therapeutic methods. Recent studies demonstrated that neuroinflammation activation plays an important role in the pathophysiology of depression. In this respect, high mobility group box 1 (HMGB1) may be a possible signaling inducer of neuroinflammation and can be a potential mechanistic and therapeutic target for depression. Herein, we review recent studies on the mechanistic and therapeutic targets of HMGB1 in depression and propose potential perspectives on this topic.
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OBJECTIVE: This study aimed to evaluate the surgical outcomes and relevant prognostic factors in patients with low-grade epilepsy-associated neuroepithelial tumors (LEAT) and, especially, to develop a scoring system to predict postoperative seizure outcomes. METHODS: The clinical data of patients who underwent epilepsy surgery for LEAT were retrospectively studied. The surgical outcomes of seizure and neurological statuses in patients were evaluated using Engel classification and modified Rankin Scale (mRS) scoring, respectively. A scoring system of seizure outcomes was constructed based on the weight of the ß-coefficient estimate of each predictor in the final multivariate predicting model of seizure outcomes. RESULTS: Of the 287 patients (106 female) enrolled, the median age was 19 years at surgery and 10 years at seizure onset, with a median duration of epilepsy of 60 months. Among 258 patients who were followed up for at least 12 months, 215 (83.3%) patients had a favorable seizure outcome (Engel class I) after surgery, and 43 (16.7%) patients had an unfavorable seizure outcome; longer duration of epilepsy, discordant magnetoencephalography (MEG) findings, and acute postoperative seizures were significantly included in the scoring system to predict unfavorable seizure outcomes, and in the scoring system, accumulated scoring of 0-19 scores was recorded, which were finally grouped into three risk levels: low risk (risk < 30%), medium risk (30% ≤ risk < 70%), and high risk (risk ≥ 70%). In addition, favorable neurological outcomes (mRS score 0-1) were recorded in 187 (72.5%) patients, while unfavorable neurological outcomes were recorded in 71 (27.5%) patients, which were significantly related to poor seizure control, older age at surgery, and longer duration of epilepsy and hospitalization time. SIGNIFICANCE: The long-term surgical outcomes of LEAT after surgery were satisfactory. A scoring system for predicting unfavorable seizure outcomes with different risk levels was developed, which could partly guide clinical treatments of LEAT.
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Epilepsia , Neoplasias Neuroepiteliomatosas , Humanos , Feminino , Adulto Jovem , Adulto , Estudos Retrospectivos , Epilepsia/cirurgia , Epilepsia/complicações , Convulsões/etiologia , Convulsões/cirurgia , Neoplasias Neuroepiteliomatosas/complicações , Neoplasias Neuroepiteliomatosas/cirurgia , Resultado do TratamentoRESUMO
Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.
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Epilepsia do Lobo Temporal , Epilepsia , Proteína HMGB1 , Humanos , Esclerose/metabolismo , Esclerose/patologia , Proteína HMGB1/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Epilepsia/cirurgia , Epilepsia/metabolismo , Gliose/patologia , Citoplasma/metabolismoRESUMO
OBJECTIVE: Rasmussen's encephalitis (RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses such as human cytomegalovirus (HCMV) has been hypothesized to be a potential trigger for RE. Interferon-induced transmembrane protein-3 (IFITM3) single-nucleotide polymorphism (SNP) rs12252 is associated with the severity of viral infection disease. This study aimed to address the possibility that HCMV infection and IFITM3 rs12252 might be associated with RE disease progression. METHODS: The expression of HCMV and IFITM3 was detected with immunohistochemical staining, in situ hybridization and immunofluorescence double staining. The genotype of IFITM3 rs12252 was detected using the Sanger sequencing method. A genetic association analysis was carried out for this SNP and HCMV antigen expression. The relationship between this SNP and the clinical characteristics of these patients was further analyzed. In in vitro study, HCMV replication in SH-SY5Y cells with overexpressed IFITM3 variant was detected by immunofluorescence and real-time RT-PCR. RESULTS: Elevated expression of HCMV and IFITM3 was observed in the brain tissue of RE patients. Moreover, the IFITM3 polymorphism rs12252-C was found to associate with HCMV high detection and rapid disease progression in RE patients with the IFITM3 rs12252-CC genotype. In vitro study showed the overexpressed IFITM3 variant was associated with HCMV high infection level. CONCLUSION: These results suggest that the IFITM3 rs12252-C is associated with the disease progression of RE patients via facilitating persistent HCMV infection in brain tissue and provides new insight into understanding the pathogenesis of RE.
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Infecções por Citomegalovirus , Citomegalovirus , Progressão da Doença , Encefalite , Proteínas de Membrana/genética , Proteínas de Ligação a RNA/genética , Células Cultivadas , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/virologia , Encefalite/genética , Encefalite/metabolismo , Encefalite/virologia , Encefalite Viral/genética , Encefalite Viral/metabolismo , Encefalite Viral/virologia , Genótipo , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Objective: Vagus nerve stimulation (VNS) is an adjunctive and well-established treatment for patients with drug-resistant epilepsy (DRE). However, it is still difficult to identify patients who may benefit from VNS surgery. Our study aims to propose a VNS outcome prediction model based on machine learning with multidimensional preoperative heart rate variability (HRV) indices. Methods: The preoperative electrocardiography (ECG) of 59 patients with DRE and of 50 healthy controls were analyzed. Responders were defined as having at least 50% average monthly seizure frequency reduction at 1-year follow-up. Time domain, frequency domain, and non-linear indices of HRV were compared between 30 responders and 29 non-responders in awake and sleep states, respectively. For feature selection, univariate filter and recursive feature elimination (RFE) algorithms were performed to assess the importance of different HRV indices to VNS outcome prediction and improve the classification performance. Random forest (RF) was used to train the classifier, and leave-one-out (LOO) cross-validation was performed to evaluate the prediction model. Results: Among 52 HRV indices, 49 showed significant differences between DRE patients and healthy controls. In sleep state, 35 HRV indices of responders were significantly higher than those of non-responders, while 16 of them showed the same differences in awake state. Low-frequency power (LF) ranked first in the importance ranking results by univariate filter and RFE methods, respectively. With HRV indices in sleep state, our model achieved 74.6% accuracy, 80% precision, 70.6% recall, and 75% F1 for VNS outcome prediction, which was better than the optimal performance in awake state (65.3% accuracy, 66.4% precision, 70.5% recall, and 68.4% F1). Significance: With the ECG during sleep state and machine learning techniques, the statistical model based on preoperative HRV could achieve a better performance of VNS outcome prediction and, therefore, help patients who are not suitable for VNS to avoid the high cost of surgery and possible risks of long-term stimulation.
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OBJECTIVE: Hemispherectomy has been used successfully for patients with medically intractable epilepsy. However, it is difficult to predict postoperative motor function. The aim of the present study was to analyze whether the preoperative asymmetry of cerebral peduncles could be used to predict motor function restoration before hemispherectomy for young patients with medically intractable epilepsy. METHODS: The clinical record and magnetic resonance imaging data of 53 patients were analyzed retrospectively. The correlation between preoperative cerebral peduncle asymmetry ratio (pCPAR) and pre- and postoperative changes in motor function was evaluated, as well as the influencing factors for pCPAR, such as duration and etiology factors. The restoration of motor function was defined as changes in pre- and postoperative hemiparesis. RESULTS: The pCPARs of patients with improved and unchanged hemiparesis were significantly greater than that of worsened patients. Patients with a pCPAR of more than 1.5 had an obvious restorative capacity of motor function of the intact hemisphere, and these patients had a lower risk of worsening hemiparesis. The duration in the improved/unchanged and worsened groups was 5.84 ± 3.85 years and 2.67 ± 2.03 years, respectively. Furthermore, there were more patients with no-progressive pathology in the group in whom pCPAR was more than 1.5. CONCLUSIONS: pCPAR is a useful and objective indicator for predicting the restoration of motor function in pediatric patients with medically intractable epilepsy before hemispherectomy. Most patients with nonprogressive pathology and a duration of more than 5 years presented with greater pCPARs, exhibited better restoration of motor function, and had less risk of worsening hemiparesis.
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Pedúnculo Cerebral/fisiopatologia , Epilepsia/fisiopatologia , Lateralidade Funcional/fisiologia , Atividade Motora/fisiologia , Recuperação de Função Fisiológica/fisiologia , Adolescente , Criança , Pré-Escolar , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Feminino , Hemisferectomia/métodos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Vagus nerve stimulation (VNS) is an adjunctive treatment for drug-resistant epilepsy (DRE). However, it is still difficult to predict which patients will respond to VNS treatment and to what extent. We aim to explore the relationship between preoperative heart rate variability (HRV) and VNS outcome. 50 healthy control subjects and 63 DRE patients who had received VNS implants and had at least one year of follow up were included. The preoperative HRV were analyzed by traditional linear methods and heart rhythm complexity analyses with multiscale entropy (MSE). DRE patients had significantly lower complexity indices (CI) as well as traditional linear HRV measurements than healthy controls. We also found that non-responders0 had significantly lower preoperative CI including Area 1-5, Area 6-15 and Area 6-20 than those in the responders0 while those of the non-responders50 had significantly lower RMSSD, pNN50, VLF, LF, HF, TP and LF/HF than the responders50. In receiver operating characteristic (ROC) curve analysis, Area 6-20 and RMSSD had the greatest discriminatory power for the responders0 and non-responders0, responders50 and non-responders50, respectively. Our results suggest that preoperative assessment of HRV by linear and MSE analysis can help in predicting VNS outcomes in patients with DRE.
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Epilepsia Resistente a Medicamentos/fisiopatologia , Frequência Cardíaca/fisiologia , Nervo Vago/fisiologia , Adolescente , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Criança , Pré-Escolar , Eletrocardiografia/métodos , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Feminino , Coração/fisiopatologia , Humanos , Masculino , Prognóstico , Convulsões/fisiopatologia , Resultado do Tratamento , Nervo Vago/metabolismo , Estimulação do Nervo Vago/métodosRESUMO
The aim of this research is to apply an approach based on phase transfer entropy (PTE) and graph theory to study the interactions between the stereo-electroencephalography (SEEG) activities recorded in multilobar origin, in order to evaluate their ability to detect the epileptogenic zone (EZ) of temporal lobe epilepsies (TLE). Forty-three patients were included in this retrospective study. Five to sixteen (median = 12) multilead electrodes were implanted per patient, and, for each patient, a sub-set of between 10 and 32 (median = 22) bipolar derivations was selected for analysis. The leads were classified into the onset leads (OLs), the early propagation leads (EPLs), and the rest of the leads (RLs). The results showed that a significantly different dynamic trend of the out/in ratio (more obvious in the gamma band) distinguishes the OLs from RLs in the 23 patients who were seizure-free not only during the ictal event (significant elevation), but also during the inter-,pre-, late-ictal periods, and especially in the post-ictal (sharp decline) state. However, in the 20 patients who were not-seizure-free, the differences between the OLs and RLs during the post-ictal period were not found in any frequency band. The dynamic trend was used to predict surgical outcome, and the results showed that the sensitivity was 91% and the specificity was 70%. In brief, this study indicates that our approach may add new and valuable information, providing efficient quantitative measures useful for localizing the EZ.
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Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico , Adolescente , Adulto , Entropia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Neuronavegação , Processamento de Sinais Assistido por Computador , Adulto JovemRESUMO
Focal cortical dysplasia type IIB is a commonly encountered subtype of developmental malformation of the cerebral cortex and is often associated with pharmacoresistant epilepsy. In this study, to investigate the molecular etiology of focal cortical dysplasia type IIB, the authors performed micro ribonucleic acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male, mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24 micro RNAs were differentially expressed in focal cortical dysplasia type IIB, and the microarray results were validated using quantitative real-time polymerase chain reaction (PCR). Then the putative target genes of the differentially expressed micro RNAs were identified by bioinformatics analysis. Moreover, biological significance of the target genes was evaluated by investigating the pathways in which the genes were enriched, and the Hippo signaling pathway was proposed to be highly related with the pathogenesis of focal cortical dysplasia type IIB.
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Epilepsia/genética , Epilepsia/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Malformações do Desenvolvimento Cortical do Grupo I/genética , Malformações do Desenvolvimento Cortical do Grupo I/metabolismo , MicroRNAs/metabolismo , Ontologias Biológicas , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Biologia Computacional , Epilepsia/tratamento farmacológico , Feminino , Perfilação da Expressão Gênica , Hipocampo/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical do Grupo I/tratamento farmacológico , MicroRNAs/genética , Análise de Sequência com Séries de OligonucleotídeosRESUMO
OBJECTIVE: To investigate the distribution of Fas and FasL in the CNS of adult rhesus. METHODS: Frozen sections were incubated in polyclonal anti-Fas and anti-FasL antibody by the immunohistochemical SP method. RESULTS: The Fas and FasL immunopositive neurons were observed in many areas. Fas immunoreactivity could be seen in the cytoplasm and processes of Purkinje cells and in the brain stem nuclei, including vestibular nucleus, dorsal nucleus of vagus and spinal nucleus of trigeminal nerve. FasL immunopositive neurons were observed in cerebral cortex, especially in pyramidal neurons of lamina I and V, cerebellar nuclei, diencephalon, and brain stem nuclei involving pontine nucleus, vestibular nucleus, cochlear nucleus, spinal nucleus of trigeminal nerve, hypoglossal nucleus, nucleus ambiguous and reticular formation. Fas and FasL immunoreactivity mainly distributed in motor neurons of spinal ventral horn and neural fibers and glia cells in white matter. They all took on brown staining in the cytoplasm and process. CONCLUSION: The distribution profiles of Fas and FasL in various areas of CNS indicate that they may fill some roles in the immune and physical function of the aforesaid anatomic
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Química Encefálica , Glicoproteínas de Membrana/metabolismo , Fatores de Necrose Tumoral/metabolismo , Receptor fas/metabolismo , Animais , Tronco Encefálico/química , Córtex Cerebral/química , Proteína Ligante Fas , Macaca mulatta , Masculino , Medula Espinal/química , Distribuição Tecidual , Núcleos Vestibulares/químicaRESUMO
OBJECTIVE: To establish spinal cord half-transection model in rhesus and investigate the Four neurological function and morphologic changes following spinal cord hemisection in rhesus. METHODS: Four cynomolgus monkeys were subjected to T-11 laminectomy and resection of a 1-mm length of hemispinal cord, while the controls underwent the identical laminectomy procedure but not the half-transection of the spinal cord. Neurological function of hindlimb was evaluated using modified Tarlov' grading, and cortical somatosensary evoked potentials (CSEP) were recorded in the 3rd postoperative month after spinal cord injury (SCI). The animals were sacrificed for histological examination. All the slices were processed with H-E staining and the number of neurons in the anterior horn of grey matter was counted. RESULTS: Irregular cavity was observed at the lesion site in the 3rd postoperative month. Distinct handicap of locomotor function in hindlimbs was observed in the half-transaction group immediately after SCI. As time went on, the locomotor function improved partially. Partial recovery of hindlimb function of adult monkey was noted in half-transection group from 14 days to 3 months after SCI, compared with that seen 24 hours postoperatively. The total number of neurons in the anterior horn of grey matter identical with hemitransection side was significantly smaller than that of the other side in the same segment (P < 0.05). CONCLUSION: A reproducible model of SCI in the nonhuman primate was established. Spontaneous partial recovery of the ipsilateral hindlimb function occurred in the monkey with spinal cord hemisected during different periods, which indicated the functional plasticity in the spinal cord after hemisection injury.
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Atividade Motora , Traumatismos da Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Membro Posterior/fisiopatologia , Locomoção , Macaca mulatta , Masculino , Plasticidade Neuronal , Recuperação de Função Fisiológica , Medula Espinal/fisiopatologiaRESUMO
OBJECTIVE: To explore the temporospatial changes of IGF-I expression in the spared dorsal root ganglia (DRG, L6) on the operated side and un-operated side, in the spinal lamina II (L3, L5, L6) and Clarke's nucleus (L3) of the adult cats that have undergone partial dorsal rhizotomy, and compare them against those of the normal adult cats so as to unveil the relation between IGF-I and the plasticity of spinal cord. METHODS: Fifteen male adult cats were divided into three groups. The cats of two groups were subjected to unilateral partial dorsal root rhizotomy (L1-L5, L7-S2 DRG were sectioned, but L6 was spared) and were sacrificed at 7 days and 14 days after operation. The bilateral L6 dorsal root ganglia and L3, L5, L6 spinal cord of all groups were made into frozen sections 20 microm thick. Then, the sections were stained by the immunohistochemistry ABC method using IGF-I (1:200, Santa Cruz) antibody. The distribution and the number of IGF-I positive neurons in bilateral spared DRG (L6) on the operated/un-operated side, in spinal lamina I (L3, L5, L6) and in Clarke' nucleus (L3) of each animal were observed and counted. All data were analyzed by one-way ANOVA, SNK-q test and paired-t test. RESULTS: (1) Seven days after partial dorsal root rhizotomy, the number of IGF-I positive neurons in spared DRG on the operated side declined as compared with that of normal group (P<0.05), but it was not significantly different from that of L6 spared DRG on the un-operated side (P>0.05). On the 14th day, the IGF-I expression in neurons of L6 DRG on the operated side was significantly lower than that of normal group and that of L6 spared DRG on the unoperated side (P<0.01), but it was not significantly different from that of the 7th day group (P>0.05). (2) There was no difference in number of IGF-I positive neuron in L3, L5, L6 spinal lamina II between normal group, 7th day post-operation group and 14th day post-operation group (P>0.05). After operation, IGF-I expression in Clarke's nucleus declined on the 7th day (P<0.05) and came back to normal level on the 14th day (P>0.05). CONCLUSION: Partial dorsal root rhizotomy can lead to the change of IGF-I expression in bilateral DRG and Clarke's nucleus, which suggests that IGF-I be related with spinal cord plasticity.
Assuntos
Gânglios Espinais/metabolismo , Fator de Crescimento Insulin-Like I/biossíntese , Medula Espinal/metabolismo , Animais , Gatos , Fator de Crescimento Insulin-Like I/genética , Masculino , Neurônios/metabolismo , Rizotomia/métodosRESUMO
BACKGROUND: Bipolar electro-coagulation has a reported efficacy in treating epilepsy involving functional cortex by pure electro-coagulation or combination with resection. However, the mechanisms of bipolar electro-coagulation are not completely known. We studied the acute cortical blood flow and histological changes after bipolar electro-coagulation in 24 patients with intractable temporal lobe epilepsy. METHODS: Twenty-four patients were consecutively enrolled, and divided into three groups according to the date of admission. The regional cortical blood flow (rCBF), electrocorticography, the depth of cortex damage, and acute histological changes (H and E staining, neuronal staining and neurofilament (NF) staining) were analyzed before and after the operation. The t-test analysis was used to compare the rCBF before and after the operation. RESULTS: The rCBF after coagulation was significantly reduced (P < 0.05). The spikes were significantly reduced after electro-coagulation. For the temporal cortex, the depth of cortical damage with output power of 2-9 W after electro-coagulation was 0.34 ± 0.03, 0.48 ± 0.06, 0.69 ± 0.06, 0.84 ± 0.09, 0.98 ± 0.08, 1.10 ± 0.11, 1.11 ± 0.09, and 1.22 ± 0.11 mm, respectively. Coagulation with output power of 4-5 W completely damaged the neurons and NF protein in the molecular layer, external granular layer, and external pyramidal layer. CONCLUSIONS: The electro-coagulation not only destroyed the neurons and NF protein, but also reduced the rCBF. We concluded that the injuries caused by electro-coagulation would prevent horizontal synchronization and spread of epileptic discharges, and partially destroy the epileptic focus.