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The application of spinal cord stimulation (SCS) and deep brain stimulation (DBS) for disorders of consciousness (DoC) has been increasingly reported. However, there is no sufficient evidence to determine how effective and safe SCS and DBS are for DoC owing to various methodological limitations. We conducted a systematic review to elucidate the safety and efficacy of SCS and DBS for DoC by systematically reviewing related literature by searching PubMed, EMBASE, Medline, and Cochrane Library. Twenty eligible studies with 608 patients were included in this study. Ten studies with 508 patients reported the efficacy of SCS for DoC, and the estimated overall effectiveness rate was 37%. Five studies with 343 patients reported the efficacy of SCS for VS, and the estimated effectiveness rate was 30%. Three studies with 53 patients reported the efficacy of SCS for MCS, and the estimated effectiveness rate was 63%. Five studies with 92 patients reported the efficacy of DBS for DoC, and the estimated overall effectiveness rate was 40%. Four studies with 63 patients reported the efficacy of DBS for VS, and the estimated effectiveness rate was 26%. Three studies with 19 patients reported the efficacy of DBS for MCS, and the estimated effectiveness rate was 74%. The adverse event rate of DoC was 8.1% and 18.2% after SCS and DBS, respectively. These results suggest that SCS and DBS can be considered reasonable treatments for DoC with considerable efficacy and safety.
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Estimulação Encefálica Profunda , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Estimulação Encefálica Profunda/métodos , Transtornos da Consciência/terapiaRESUMO
Deep brain stimulation (DBS) is a reversible treatment for chorea-acanthocytosis (ChAc). Its safety and efficacy remain elusive due to the low prevalence of ChAc. We aimed to investigate the safety and efficacy of DBS for ChAc by systematically reviewing literature through PubMed and EMBASE. Inclusion criteria were reports on the efficacy or safety of DBS for ChAc and English language articles, and exclusion criteria were other movement disorders, non-human subjects, and studies without original data. Most studies were published as case reports, and we therefore pooled these cases in one cohort. Twenty studies with 34 patients were included. The mean age of symptom onset was 29.3 years (range, 17-48). The median follow-up was 12 months (range, 2-84). Twenty-nine patients underwent GPi-DBS, two received STN-DBS, and one underwent Vop-DBS. Electrodes were implanted into the ventralis oralis complex of the thalamus and the pallidal in two patients. Symptoms seemed to be easier relieved in chorea (88.5%) and dystonia (76.9%) but dysarthria of most patients (85.7%) was no response after DBS. The Unified Huntington's Disease Rating Scale-Motor Score was used to assess the efficacy of DBS in 25 patients; the mean score decreased from 43.2 to 22.3 and the median improvement rate was 46.7%. Of 24 patients with data on adverse events, complications occurred in 9 patients (37.5%; mostly transient and mild events). DBS is a promising treatment for ChAc with satisfactory efficacy and safety based on the review. Pallidal and thalamic DBS have been applied in ChAc; GPi-DBS seems to be more widely used.
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Estimulação Encefálica Profunda , Distonia , Neuroacantocitose , Distonia/terapia , Globo Pálido , Humanos , Neuroacantocitose/terapia , Resultado do TratamentoRESUMO
Deafferentation pain (DP), a typical neuropathic pain, occurs due to peripheral or central sensory nerve injury, which causes abnormal discharge of the upstream neurons or C fibers. Current treatment methods for DP have multiple side effects. Bone marrow mesenchymal stem cells (BMSC) have been used to treat neuropathic pain because of their ability to regulate neuroinflammation. Glial cell-derived neurotrophic factor (GDNF) is a neurotrophic mediator that exerts neuroprotective effects in neurological diseases. In this study, we investigated whether DP could be alleviated by BMSCs and the underlying mechanism. In vitro study, microglia was stimulated by lipopolysaccharide and then co-cultured with BMSC, GDNF or siRNA GDNF-BMSC. In vivo study, BMSC or siRNA GDNF-BMSC was transplanted intramedullarily on the 21st day after DP surgery. The expression of inflammatory-related factors were detected by RT-PCR and ELISA, RT-PCR,flow cytometry and immunofluorescence staining were performed to detect the expression of microglial surface markers, and Western blot was used to detect the expression levels of p-NF-kb, pPI3K, and pAKT. The pain-related behavioral changes were detected 7 days after transplantation. ELISA and RT-PCR results showed that the production of inflammatory cytokines in lipopolysaccharide-stimulated microglia and DP model plasma was downregulated, while anti-inflammatory mediators were upregulated significantly following pretreatment with BMSCs or GDNF. Flow cytometry, immunofluorescence staining, and RT-PCR results showed that BMSCs inhibited the microglial M1 phenotype and promoted the M2 phenotype by secreting GDNF. Furthermore, modulation functions of BMSCs involve inhibiting NF-κB while promoting PI3K /AKT signaling pathway activation. We found that our in vivo DP model was completely deafferent and BMSC administration clearly alleviated symptoms of DP. This function was also, at least partly, achieved by GDNF. The present studies demonstrate that BMSC can inhibit neuroinflammation by transforming microglial destructive M1 phenotype into regenerative M2 phenotype, and thus alleviate DP,likely by suppressing the NF-κB signaling pathway while promoting the PI3K/AKT signaling pathway activation through producing GDNF. The present findings are in support of the potential therapeutic application of BMSCs and the pharmaceutical application of GDNF for DP.
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Causalgia/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Células-Tronco Mesenquimais/metabolismo , Microglia/metabolismo , Transdução de Sinais/fisiologia , Animais , Células da Medula Óssea/metabolismo , Regulação para Baixo , Masculino , Transplante de Células-Tronco Mesenquimais , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Self-management is important for patients suffering from cerebrovascular events after neurosurgical procedures. An increasing number of artificial intelligence (AI)-assisted tools have been used in postoperative health management. ChatGPT is a new trend dialog-based chatbot that could be used as a supplemental tool for seeking health information. Responses from ChatGPT version 3.5 and 4.0 toward 13 questions raised by experienced neurosurgeons were evaluated in this exploratory study for their consistency and appropriateness blindly by the other three neurosurgeons. The readability of response text was investigated quantitively by word count and the Gunning Fog and Flesch-Kincaid indices. Results showed that the chatbot could provide relatively stable output between the two versions on consistency and appropriateness (χ² = 0.348). As for readability, there was a higher demand for readers to comprehend the output text in the 4.0 version (more counts of words; lower Flesch-Kincaid reading ease score; and higher Flesch-Kincaid grade level). In general, the capacity of ChatGPT to deliver effective health information is still under debate.
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Objectives: The purpose of this paper is to provide a mini-review covering the recent progress in human and animal studies on local field potentials (LFPs) of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). Materials and methods: PubMed and EMBASE were searched to identify related studies. Inclusion criteria were (1) reported the LFPs on OCD or MDD, (2) published in English, and (3) human or animal studies. Exclusion criteria were (1) review or meta-analysis or other literature types without original data and (2) conference abstract without full text. Descriptive synthesis of data was performed. Results: Eight studies on LFPs of OCD containing 22 patients and 32 rats were included: seven were observational studies with no controls, and one animal study included a randomized and controlled phase. Ten studies on LFPs of MDD containing 71 patients and 52 rats were included: seven were observational studies with no controls, one study with control, and two animal studies included a randomized and controlled phase. Conclusion: The available studies revealed that different frequency bands were associated with specific symptoms. Low frequency activity seemed to be closely related to OCD symptoms, whereas LFPs findings in patients with MDD were more complicated. However, limitations of recent studies restrict the drawing of definite conclusions. Combined with other measures such as Electroencephalogram, Electrocorticography, or Magnetoencephalography and long-term recordings in various physiological states (rest state, sleep state, task state) could help to improve the understanding of potential mechanisms.
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Intracerebral hemorrhage (ICH) is a neurological disease with high mortality and disability. Recent studies showed that white matter injury (WMI) plays an important role in motor dysfunction after ICH. WMI includes WMI proximal to the lesion and WMI distal to the lesion, such as corticospinal tract injury located at the cervical enlargement of the spinal cord after ICH. Previous studies have tended to focus only on gray matter (GM) injury after ICH, and fewer studies have paid attention to WMI, which may be one of the reasons for the poor outcome of previous drug treatments. Microglia and astrocyte-mediated neuroinflammation are significant mechanisms responsible for secondary WMI following ICH. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation, has been shown to exacerbate neuroinflammation and brain injury after ICH. Moreover, NLRP3 inflammasome is activated in microglia and astrocytes and exerts a vital role in microglia and astrocytes-mediated neuroinflammation. We speculate that NLRP3 inflammasome activation is closely related to the polarization of microglia and astrocytes and that NLRP3 inflammasome activation may exacerbate WMI by polarizing microglia and astrocytes to the pro-inflammatory phenotype after ICH, while NLRP3 inflammasome inhibition may attenuate WMI by polarizing microglia and astrocytes to the anti-inflammatory phenotype following ICH. Therefore, NLRP3 inflammasome may act as leveraged regulatory fulcrums for microglia and astrocytes polarization to modulate WMI and WM repair after ICH. This review summarized the possible mechanisms by which neuroinflammation mediated by NLRP3 inflammasome exacerbates secondary WMI after ICH and discussed the potential therapeutic targets.
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Lesões Encefálicas , Substância Branca , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Substância Branca/metabolismo , Substância Branca/patologia , Hemorragia Cerebral/complicações , Lesões Encefálicas/tratamento farmacológico , Microglia/metabolismoRESUMO
OBJECTIVE: Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD. METHODS: Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAc-ALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG. RESULTS: The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude. CONCLUSIONS: These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD. Clinical trial registration no.: NCT02398318 (ClinicalTrials.gov).
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Estimulação Encefálica Profunda , Transtorno Obsessivo-Compulsivo , Humanos , Núcleo Accumbens , Cápsula Interna , Transtorno Obsessivo-Compulsivo/terapia , Eletrodos , Resultado do TratamentoRESUMO
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) (NAc-DBS) is an effective solution to refractory obsessive-compulsive disorder (OCD). However, evidence for the neurobiological mechanisms of OCD and the effect of NAc-DBS is still lacking. One hypothesis is that the electrophysiological activities in the NAc are modulated by DBS, and another hypothesis is that the activities of neurotransmitters in the NAc are influenced by DBS. To investigate these potential alterations, rats with quinpirole (QNP)- induced OCD were treated with DBS of the core part of NAc. Then, extracellular spikes (SPK) and local field potentials (LFP) in the NAc were recorded, and the levels of relevant neurotransmitters and related proteins were measured. Analysis of SPK revealed that the firing rate was decreased and the firing pattern was changed after NAc-DBS, and analysis of LFP showed that overall power spectral density (PSD) levels were reduced after NAc-DBS. Additionally, we found that the relative powers of the theta band, alpha band and beta band were increased in OCD status, while the relative powers of the delta band and gamma band were decreased. This pathological pattern of power distribution was reformed by NAc-DBS. Furthermore, we found that the local levels of monoamines [dopamine (DA) and serotonin (5-HT)] and amino acids [glutamate (Glu) and gamma-aminobutyric acid (GABA)] in the NAc were increased in OCD status, and that the expression of the two types of DA receptors in the NAc exhibited an opposite change. These abnormalities could be reversed by NAc-DBS. These findings provide a more comprehensive understanding about the function of the NAc in the pathophysiology of OCD and provide more detailed evidence for the potential effect of NAc-DBS.
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Intracerebral hemorrhage (ICH) has a high mortality and disability rate. Fewer studies focus on white matter injury (WMI) after ICH, especially the corticospinal tract (CST) injury located in the spinal cord, which correlates with motor impairments. Recent studies have shown that gut microbiota dysbiosis occurs after ICH. Furthermore, NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. However, no direct and causal correlation among NLRP3 inflammasome inhibition, altered gut microbiota, and CST injury following ICH has been reported. This study aimed to investigate the effect of MCC950, a selective NLRP3 inflammasome inhibitor, on the gut microbiota and CST injury after ICH. We observed that compared with the sham group, the members of Firmicutes, such as Faecalibaculum and Dubosiella, were depleted in the ICH + Vehicle group, whereas the members of Proteobacteria and Campilobacterota were enriched, such as Enterobacter and Helicobacter. After treatment with MCC950, the Bacteroides, Bifidobacterium and Paenibacillus were relatively abundant in the gut flora of mice. Moreover, we observed CST injury located in cervical enlargement of the spinal cord, and MCC950 alleviated it. Furthermore, treatment with MCC950 decreased the mNSS score and brain water content in ICH. Taken together, the present study showed that MCC950 modulated gut microbiota, effectively attenuated CST injury located in cervical enlargement of the spinal cord, and ameliorated neurological deficits after ICH. This study provided a novel report that links NLRP3 inflammasome inhibition, gut microbiota alteration and CST injury following ICH and profound implications for ICH treatment.
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Lesões Encefálicas , Microbioma Gastrointestinal , Animais , Lesões Encefálicas/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Modelos Animais de Doenças , Inflamassomos , Inflamação/complicações , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Tratos PiramidaisRESUMO
Intracerebral hemorrhage (ICH) is the most fatal subtype of stroke with high disability and high mortality rates, and there is no effective treatment. The predilection site of ICH is in the area of the basal ganglia and internal capsule (IC), where exist abundant white matter (WM) fiber tracts, such as the corticospinal tract (CST) in the IC. Proximal or distal white matter injury (WMI) caused by intracerebral parenchymal hemorrhage is closely associated with poor prognosis after ICH, especially motor and sensory dysfunction. The pathophysiological mechanisms involved in WMI are quite complex and still far from clear. In recent years, the neuroprotection and repairment capacity of mesenchymal stem cells (MSCs) has been widely investigated after ICH. MSCs exert many unique biological effects, including self-recovery by producing growth factors and cytokines, regenerative repair, immunomodulation, and neuroprotection against oxidative stress, providing a promising cellular therapeutic approach for the treatment of WMI. Taken together, our goal is to discuss the characteristics of WMI following ICH, including the mechanism and potential promising therapeutic targets of MSCs, aiming at providing new clues for future therapeutic strategies.
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Intracerebral hemorrhage (ICH) is the most fatal subtype of stroke; there is still a lack of effective treatment. Microglia are a major component of the innate immune system, and they respond to acute brain injury by activating and forming classic M1-like (pro-inflammatory) or alternative M2-like (anti-inflammatory) phenotype. The existence of the polarization indicates that the role of microglia in disease's progression and recovery after ICH is still unclear, perhaps involving microglial secretion of anti-inflammatory or pro-inflammatory cytokines and chemokines. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is considered to be the main participant in neuroinflammation. Recent evidence has shown that NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. Furthermore, previous studies have reported that NLRP3 inflammasome is mainly present in microglia, so we speculate that its activation may be strongly associated with microglial polarization. Many scholars have investigated the role of brain injury caused by NLRP3 inflammasome after ICH, but the precise operating mechanisms remain uncertain. This review summarized the activation mechanism of NLRP3 inflammasome after ICH and the possible mechanism of NLRP3 inflammasome promoting neuroinflammation and aggravating nerve injury and discussed the relevant potential therapeutic targets.