RESUMO
Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS) (SOD1G93A) and Huntington's disease (R6/2) models. Cortical resting [K+]e correlated inversely with neuronal density and the [K+]e buffering rate but correlated positively with the predicted neuronal firing rate. Screening of astrocyte-selective genomic datasets revealed a number of potassium channel genes that were downregulated in these disease models but not in normal ageing. In particular, the inwardly rectifying potassium channel Kcnj10 was downregulated in ALS and Huntington's disease models but not in normal ageing, while Fxyd1 and Slc1a3, each of which acts as a negative regulator of potassium uptake, were each upregulated by astrocytes in both Alzheimer's disease and ALS models. Chronic elevation of [K+]e in response to changes in gene expression and the attendant neuronal hyperexcitability may drive the neuronal loss characteristic of these neurodegenerative diseases. These observations suggest that the dysregulation of extracellular K+ homeostasis in a number of neurodegenerative diseases could be due to aberrant astrocytic K+ buffering and as such, highlight a fundamental role for glial dysfunction in neurodegeneration.
Assuntos
Envelhecimento , Doenças Neurodegenerativas , Potássio , Animais , Potássio/metabolismo , Envelhecimento/metabolismo , Camundongos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Camundongos Transgênicos , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Humanos , Modelos Animais de Doenças , Córtex Cerebral/metabolismo , Doença de Huntington/metabolismo , Doença de Huntington/genética , Feminino , Astrócitos/metabolismoRESUMO
The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.
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Adaptação Fisiológica , Evolução Molecular , Genoma , Genômica , Mamíferos/fisiologia , Filogenia , Termogênese/genética , Animais , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Seleção Genética , Semaforinas/genética , Semaforinas/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
The Atlantic herring is a model species for exploring the genetic basis for ecological adaptation, due to its huge population size and extremely low genetic differentiation at selectively neutral loci. However, such studies have so far been hampered because of a highly fragmented genome assembly. Here, we deliver a chromosome-level genome assembly based on a hybrid approach combining a de novo Pacific Biosciences (PacBio) assembly with Hi-C-supported scaffolding. The assembly comprises 26 autosomes with sizes ranging from 12.4 to 33.1 Mb and a total size, in chromosomes, of 726 Mb, which has been corroborated by a high-resolution linkage map. A comparison between the herring genome assembly with other high-quality assemblies from bony fishes revealed few inter-chromosomal but frequent intra-chromosomal rearrangements. The improved assembly facilitates analysis of previously intractable large-scale structural variation, allowing, for example, the detection of a 7.8-Mb inversion on Chromosome 12 underlying ecological adaptation. This supergene shows strong genetic differentiation between populations. The chromosome-based assembly also markedly improves the interpretation of previously detected signals of selection, allowing us to reveal hundreds of independent loci associated with ecological adaptation.
Assuntos
Mapeamento Cromossômico , Peixes/genética , Genoma , Adaptação Fisiológica/genética , Animais , Seleção GenéticaRESUMO
Spontaneous waves of cortical spreading depolarization (CSD) are induced in the setting of acute focal ischemia. CSD is linked to a sharp increase of extracellular K+ that induces a long-lasting suppression of neural activity. Furthermore, CSD induces secondary irreversible damage in the ischemic brain, suggesting that K+ homeostasis might constitute a therapeutic strategy in ischemic stroke. Here we report that adrenergic receptor (AdR) antagonism accelerates normalization of extracellular K+, resulting in faster recovery of neural activity after photothrombotic stroke. Remarkably, systemic adrenergic blockade before or after stroke facilitated functional motor recovery and reduced infarct volume, paralleling the preservation of the water channel aquaporin-4 in astrocytes. Our observations suggest that AdR blockers promote cerebrospinal fluid exchange and rapid extracellular K+ clearance, representing a potent potential intervention for acute stroke.
Assuntos
Antagonistas Adrenérgicos/farmacologia , Isquemia Encefálica/metabolismo , Neuroproteção/efeitos dos fármacos , Acidente Vascular Cerebral/metabolismo , Animais , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Potássio/metabolismoRESUMO
KEY MESSAGE: We provided a chromosome-length assembly of B. nigra and show the comprehensive chromosome-scale variations among Brassica genomes. Chromosome-level assembly of the Brassica species, which include many important crops, is essential for the agricultural and evolutionary studies. While the present B. nigra chromosomes was connected with genetic map of B. juncea, hindering the comparative analysis of the B chromosomes. Here we present a chromosome-length B. nigra assembly constructed with Hi-C connections and its variations on chromosome level compared with other Brassica species. We produced an assembly of 484 Mb annotated with 51,829 genes, of which 393 Mb were anchored onto 8 chromosomes, taking 81.26% of the assembly. Comparison of the B chromosomes shows high concordance of the two B. nigra assemblies and reveals comprehensive variations of the B chromosomes after polyploidization and gene loss in syntenic regions. Chromosome blocks with variations have lower gene density and higher TE content. Furthermore, we compared the chromosomes of the three major Brassica diploids, which showed that most of the variations between B and A/C had completed before A/C divergence and there are more variations on C chromosomes after their divergence. In summary, our work presents a chromosome-length assembly of B. nigra and comprehensive comparative analysis of the Brassica chromosomes, which provides a useful reference for other studies and comprehensive information of Brassica chromosome evolution.
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Brassica/genética , Cromossomos de Plantas , Tamanho do Genoma , Genoma de Planta/genética , Brassica/classificação , Mapeamento Cromossômico , Elementos de DNA Transponíveis , Diploide , Evolução Molecular , Frequência do Gene , Genes de Plantas/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Sintenia , Sequenciamento Completo do GenomaRESUMO
OBJECTIVE: In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. METHODS: CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. RESULTS: Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-ß was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. INTERPRETATION: We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates.
Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Taxa de Depuração Metabólica/fisiologia , Envelhecimento/patologia , Animais , Aquaporina 4/metabolismo , Encéfalo/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neuroglia/metabolismo , Neuroglia/patologiaRESUMO
Recent studies have shown that cerebellar Bergmann glia display coordinated Ca(2+) transients in live mice. However, the functional significance of Bergmann glial Ca(2+) signaling remains poorly understood. Using transgenic mice that allow selective stimulation of glial cells, we report here that cytosolic Ca(2+) regulates uptake of K(+) by Bergmann glia, thus providing a powerful mechanism for control of Purkinje cell-membrane potential. The decline in extracellular K(+) evoked by agonist-induced Ca(2+) in Bergmann glia transiently increased spike activity of Purkinje cells in cerebellar slices as well as in live anesthetized mice. Thus, Bergmann glia play a previously unappreciated role in controlling the membrane potential and thereby the activity of adjacent Purkinje cells.
Assuntos
Sinalização do Cálcio/fisiologia , Cerebelo/citologia , Potenciais da Membrana/fisiologia , Neuroglia/fisiologia , Potássio/metabolismo , Células de Purkinje/metabolismo , Potenciais de Ação/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microeletrodos , Microscopia Confocal , Células de Purkinje/citologia , Ratos , Ratos Sprague-DawleyRESUMO
Calcium signaling represents the principle pathway by which astrocytes respond to neuronal activity. General anesthetics are routinely used in clinical practice to induce a sleep-like state, allowing otherwise painful procedures to be performed. Anesthetic drugs are thought to mainly target neurons in the brain and act by suppressing synaptic activity. However, the direct effect of general anesthesia on astrocyte signaling in awake animals has not previously been addressed. This is a critical issue, because calcium signaling may represent an essential mechanism through which astrocytes can modulate synaptic activity. In our study, we performed calcium imaging in awake head-restrained mice and found that three commonly used anesthetic combinations (ketamine/xylazine, isoflurane, and urethane) markedly suppressed calcium transients in neocortical astrocytes. Additionally, all three anesthetics masked potentially important features of the astrocyte calcium signals, such as synchronized widespread transients that appeared to be associated with arousal in awake animals. Notably, anesthesia affected calcium transients in both processes and soma and depressed spontaneous signals, as well as calcium responses, evoked by whisker stimulation or agonist application. We show that these calcium transients are inositol 1,4,5-triphosphate type 2 receptor (IP(3)R2)-dependent but resistant to a local blockade of glutamatergic or purinergic signaling. Finally, we found that doses of anesthesia insufficient to affect neuronal responses to whisker stimulation selectively suppressed astrocyte calcium signals. Taken together, these data suggest that general anesthesia may suppress astrocyte calcium signals independently of neuronal activity. We propose that these glial effects may constitute a nonneuronal mechanism for sedative action of anesthetic drugs.
Assuntos
Anestesia Geral , Anestésicos/farmacologia , Astrócitos/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinapses/metabolismo , Vigília/efeitos dos fármacos , Animais , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Camundongos , Camundongos KnockoutRESUMO
Adenosine is a potent anticonvulsant acting on excitatory synapses through A1 receptors. Cellular release of ATP, and its subsequent extracellular enzymatic degradation to adenosine, could provide a powerful mechanism for astrocytes to control the activity of neural networks during high-intensity activity. Despite adenosine's importance, the cellular source of adenosine remains unclear. We report here that multiple enzymes degrade extracellular ATP in brain tissue, whereas only Nt5e degrades AMP to adenosine. However, endogenous A1 receptor activation during cortical seizures in vivo or heterosynaptic depression in situ is independent of Nt5e activity, and activation of astrocytic ATP release via Ca(2+) photolysis does not trigger synaptic depression. In contrast, selective activation of postsynaptic CA1 neurons leads to release of adenosine and synaptic depression. This study shows that adenosine-mediated synaptic depression is not a consequence of astrocytic ATP release, but is instead an autonomic feedback mechanism that suppresses excitatory transmission during prolonged activity.
Assuntos
Adenosina/metabolismo , Potenciais Pós-Sinápticos Excitadores/fisiologia , Retroalimentação Fisiológica/fisiologia , Neurônios/metabolismo , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Difosfato de Adenosina/análogos & derivados , Difosfato de Adenosina/farmacologia , Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiologia , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas de Patch-Clamp , Receptor A1 de Adenosina/metabolismo , Convulsões/metabolismo , Convulsões/fisiopatologiaRESUMO
Astrocytes in hippocampal slices can dynamically regulate synaptic transmission in a process mediated by increases in intracellular Ca(2+). However, it is debated whether astrocytic Ca(2+) signals result in release of glutamate. We here compared astrocytic Ca(2+) signaling triggered by agonist exposure versus photolysis side by side. Using transgenic mice in which astrocytes selectively express the MrgA1 receptor, we found that receptor-mediated astrocytic Ca(2+) signaling consistently triggered neuronal hyperpolarization and decreased the frequency of miniature excitatory postsynaptic currents (EPSCs). In contrast, photolysis of caged Ca(2+) (o-nitrophenyl-EGTA) in astrocytes led to neuronal depolarization and increased the frequency of mEPSCs through a metabotropic glutamate receptor-mediated pathway. Analysis of transgenic mice in which astrocytic vesicular release is suppressed (dominant-negative SNARE mice) and pharmacological manipulations suggested that glutamate is primarily released by opening of anion channels rather than exocytosis. Combined, these studies show that photolysis but not by agonists induced astrocytic Ca(2+) signaling triggers glutamate release.
Assuntos
Astrócitos/metabolismo , Sinalização do Cálcio/genética , Ácido Glutâmico/metabolismo , Fotólise , Animais , Regulação para Baixo/genética , Potenciais Pós-Sinápticos Excitadores/genética , Feminino , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Inibição Neural/genética , Técnicas de Cultura de Órgãos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteínas SNARE/deficiência , Proteínas SNARE/genéticaRESUMO
A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here showed that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from glial fibrillary acidic protein-green fluorescent protein reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field excitatory postsynaptic current. Analysis of Ca(2+) signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice versus in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible.
Assuntos
Astrócitos/metabolismo , Regulação da Expressão Gênica/fisiologia , Gliose/patologia , Hipocampo/citologia , Hipocampo/lesões , Animais , Animais Recém-Nascidos , Aquaporina 4/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/ultraestrutura , Cálcio/metabolismo , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/etiologia , Glicogênio/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Técnicas In Vitro , Ácido Láctico/metabolismo , Masculino , Camundongos , NAD/metabolismo , Compostos de Amônio Quaternário/farmacologiaRESUMO
BACKGROUND: This work aimed to evaluate the efficacy of virtual reality (VR) technology in neurosurgical anatomy through a comparison of the virtual 3D microanatomy of the suboccipital vertebral arteries and their bony structures as part of the resection of tumors in the craniovertebral junction (CVJ) of 20 patients compared to the actual microanatomy of the vertebral arteries of 15 cadaveric headsets. MATERIAL AND METHODS: The study was conducted with 2 groups of data: a VR group composed of 20 clinical cases and a physical body group (PB group) composed of 15 cadaveric headsets. In the VR group, the dissection and measurements of the vertebral arteries were simulated on a Dextroscope. In the PB group, the vertebral arteries in the cadaver heads were examined under a microscope and anatomical measurements of VA and bony structures were performed. The length and course of the vertebral arteries and its surrounding bony structures in each group were compared. RESULTS: The distances from the inferior part of the transverse process foramen (TPF) of C1 to the inferior part of TPF of C2 were 17.68±2.86 mm and 18.4±1.82 mm in the PB and VR groups, respectively. The distances between the middle point of the posterior arch of the atlas and the medial intersection of VA on the groove were 17.35±2.23 mm in the PB group and 18.13±2.58 mm in the VR group. The distances between the middle line and the entrance of VA to the lower rim of TPF of Atlas were 28.64±2.67 mm in PB group and 29.23±2.89 mm in VR group. The diameters of the vertebral artery (VA) at the end of the groove and foramen of C2 transverse process were 4.02±046 mm and 4.25±0.51 mm, respectively, in the PB group and 3.54±0.44 mm and 4.47±0.62 mm, respectively, in VR group. The distances between the VA lumen center and midline of the foramen magnum at the level of dural penetration was 10.4±1.13 mm in the PB group and 11.5±1.34 mm in the VR group (P>0.05). CONCLUSIONS: VR technology can accurately simulate the anatomical features of the suboccipital vertebral arteries and their bony structures, which facilitates the planning of individual surgeries in the CVJ.
Assuntos
Procedimentos Neurocirúrgicos/métodos , Lobo Occipital/irrigação sanguínea , Coluna Vertebral/anatomia & histologia , Interface Usuário-Computador , Artéria Vertebral/anatomia & histologia , Adulto , HumanosRESUMO
Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1. Moreover, we found that Pi uptake by PiT2, and its facilitation by PFBC-associated galactosidase MYORG, were required for the high Pi transport capacity of astrocytes. Finally, brain calcification was suppressed by astrocyte-specific PiT2 re-expression in Pit2-KO mice. Thus, astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis, and elevating astrocytic Pi transporter function represents a potential therapeutic strategy for reducing brain calcification.
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Background: Depression is an independent factor to predict the hospitalization and mortality in the chronic HF patients. Citalopram is known as an effective drug for depression treatment. Currently, there is no specific recommendation in the HF guidelines for the treatment of psychological comorbidity. In recent years, many studies have shown that the citalopram may be safe in treating of chronic HF with depression. Objective: To evaluate the efficacy and safety of the citalopram in the treatment of elderly chronic HF combined with depression. Methods: PubMed, EMBASE, Cochrane, Web of Science, CNKI, VIP, CBM, and Wanfang were searched from their inception to May 2022. In the treatment of elderly chronic HF combined with depression, randomized controlled studies of the citalopram were included. Independent screening and extraction of data information were conducted by two researchers, and the quality was assessed by the Cochrane bias risk assessment tool. Review manager 5.4.1 was employed for statistical analysis. Results: The results of meta-analysis prove that the citalopram treatment for depressed patients with chronic HF has a benefit for HAMD-24 (MD: -8.51, 95% CI: -10.15 to -6.88) and LVEF (MD: 2.42, 95% CI: 0.51 to 4.33). Moreover, the score of GDS decreases, and NT-proBNP (MD: -537.78, 95% CI: -718.03 to -357.54) is improved. However, the comparison with the control group indicates that there is no good effect on HAMD-17 (MD: -5.14, 95% CI: -11.60 to 1.32), MADRS (MD: -1.57, 95% CI: -3.47 to 0.32) and LVEDD (MD: -1.45, 95% CI: -3.65 to -0.76). No obvious adverse drug reactions were observed. Conclusion: Citalopram treatment for depressed patients with chronic HF has a positive effect on LVEF and NT-proBNP. It can alleviate HAMD-24 and GDS, but the relative benefits for LVEDD, HAMD-17 and MADRS still need to be verified.Systematic Review Registration: PROSPERO [CRD42021289917].
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Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity using tetrodotoxin (TTX) and voltage-gated Ca(2+) channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca(2+) in astrocytes. Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling. Our results show an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.
Assuntos
Astrócitos/fisiologia , Sinalização do Cálcio , Epilepsia/fisiopatologia , Ácido Glutâmico/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Astrócitos/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Hipocampo , Fotólise , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effects of intensive family-centered health education on the awareness rate, diagnosis, and treatment of post-stroke depression (PSD) in community families. METHODS: Elderly patients (60-90 years) from 20 community service centers affiliated with the Department of Neurology and the Medical Association of Tongling Municipal Hospital who had been diagnosed with stroke between January 2017 and June 2020 were screened using the hospital and community electronic medical record system. In this randomized cluster trial, 119 patients from 10 communities were assigned as the control group and received routine community treatment, while 126 patients from the other 10 communities were assigned as the experimental group and received routine treatment plus family-centered intensive health education. After 12 months of medical intervention, the assessment of PSD in the two groups was performed by a neurologist and a psychiatrist, both blind to the study design, using the Hamilton Rating Scale for Depression. RESULTS: The awareness rates of the causes, clinical manifestations, treatment plan, and family care of PSD in the experimental group were 88.89, 91.30, 93.65, and 92.06%, respectively. In the control group, the awareness rates of these parameters were 72.27, 69.75, 71.43, and 65.55%, respectively, and the differences between the two groups were statistically significant (P < 0.05). In the experimental group, the rates of PSD diagnosis, prompt medical attendance, drug treatment compliance, and psychotherapeutic treatment compliance were 27.78, 22.22, 18.25, and 11.90%, respectively. In the control group, the rates of these parameters were 13.79, 6.03, 3.48, and 1.72%, respectively, and the differences between the two groups were statistically significant (P < 0.05). CONCLUSION: Intensive family-centered health education can improve the level of knowledge of PSD in the community, promote the timely treatment and diagnosis of PSD in patients, and improve the compliance rates of drug therapy and psychotherapy, so this is worthy of promotion.
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Depressão , Acidente Vascular Cerebral , Humanos , Idoso , Depressão/diagnóstico , Acidente Vascular Cerebral/complicações , Educação em SaúdeRESUMO
OBJECTIVE: To explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS). METHODS: The serum IL-6 and hs-CRP levels of the patients in both the experimental group and the standard group were measured before thrombolysis and at 1 and 24 h afterwards. National Institute of Health Stroke Scale (NIHHS) scores were also recorded at the same time points as well as at 10 and 90 d after thrombolysis, and modified Rankin Scale (mRS) scores were calculated before thrombolysis and at 10 and 90 d afterwards. The differences in all these observations before and after thrombolysis were then investigated. RESULTS: (1) The levels of serum IL-6 and hs-CRP in the experimental group and the standard group were higher than those in the healthy control group before thrombolysis (P < 0.05), indicating that higher levels of hs-CRP and IL-6 are risk factors for WUS (P < 0.05). (2) There were no significant differences in the serum hs-CRP and IL-6 levels of the patients in the experimental and standard groups before thrombolysis (P > 0.05). (3) The serum IL-6 and hs-CRP levels were positively correlated with the NIHHS scores in both the experimental group and the standard group (P < 0.05), and they correlated with the mRS scores at 90 d. CONCLUSIONS: Interleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke, and the combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.
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AVC Isquêmico , Acidente Vascular Cerebral , Proteína C-Reativa/metabolismo , Humanos , Interleucina-6 , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversosRESUMO
Background: Spinal dural arteriovenous fistula (SDAVF) is an extremely rare spinal vascular malformation. As SDAVF exhibits no specific clinical manifestations nor diverse imaging results, it is easily misdiagnosed, resulting in delayed treatment and irreversible neurological damage. Most patients were initially misdiagnosed, but there were few reports on reducing misdiagnosis. Methods: A total of 32 consecutive patients, who presented to our institution (Shanghai Deji Hospital) with SDAVF between June 2013 and January 2016 were retrospectively analyzed. Data were collected on demographics, clinical presentation, imaging findings, follow-up, and clinical outcomes. The Aminoff-Logue scale (ALS) was used to assess clinical outcomes. Results: Of the 32 enrolled patients (3 females, mean age 59.1±3.8 years), 23 patients (71.9%) were misdiagnosed as acute myelitis (11 patients), intramedullary tumors (6 patients), lumbar disc herniation (4 patients), and other conditions (2 patients). All patients underwent surgical procedures under electrophysiological monitoring. Fistulas were found in all 32 patients and were successfully occluded. The mean follow-up period was 19.22±8.21 months (ranging from 2 weeks to 30 months). One year later, 20 patients underwent magnetic resonance imaging (MRI), and 14 showed no T2 edema, and the edema was relieved in 6 patients. A total of 10 patients underwent enhancement MRI and no enhancement signs were detected. Among the 27 patients with long-time follow-up, the fistula had no residual or recurrence, 21 patients showed decreased ALS scores (P<0.05). Six patients exhibited nonsignificant improvement. No aggravating patient was found. Prognosis differed significantly between patients with ALS <6 and those with ALS ≥6 (P<0.05). Conclusions: Spinal angiography should be performed with full intubation, and microcatheter angiography can reduce misdiagnosis. SDAVF must be differentiated from acute myelitis, intramedullary tumor, and other spinal vascular malformations. Microsurgical treatment is effective with a low recurrence rate.
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BACKGROUND: The control of diseases related to atrial fibrillation (AF) may reduce the occurrence of AF, delay progression, and reduce complications, which is beneficial to the prevention and treatment of AF. An increasing number of studies have shown that AF is associated with depression. However, to date, there has not been a bibliometric analysis to examine this field systematically. Our study aimed to visualize the publications to determine the hotspots and frontiers in research on AF and depression and provide guidance and reference for further study. METHODS: Publications about AF and depression between 2001 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace 5.8. R1, VOSviewer 1.6.16, and Excel 2019 software tools were used to conduct this bibliometric study. RESULTS: In total, 159 articles and reviews were analyzed. The number of publications has been increased sharply since 2018. David D. McManus had the largest number of publications. The most prolific country was the USA with 54 publications but the centrality was <0.1. The most prolific institution was Northeastern University. Three clusters were formed based on keywords: The first cluster was composed of atrial fibrillation, depression, anxiety, symptoms, ablation, and quality of life, et al. The second cluster were risk, prevalence, mortality, heart failure, association, et al. While the third cluster included anticoagulation, impact, stroke, management, warfarin, et al. After 2019, stroke and prediction are the keywords with strongest citation bursts. CONCLUSION: Research on AF and depression is in its infancy. Cooperation and exchanges between countries and institutions must be strengthened in the future. The effect of depression on prevalence and mortality in AF, depression on ablation in AF, and impact of depression on anticoagulation treatment in AF have been the focus of current research. Stroke prevention (including anticoagulant therapy) is the research frontier, which may still be the focus of research in the future.
RESUMO
Secondary injury exacerbates the extent of spinal cord insults, yet the mechanistic basis of this phenomenon has largely been unexplored. Here we report that broad regions of the peritraumatic zone are characterized by a sustained process of pathologic, high ATP release. Spinal cord neurons expressed P2X7 purine receptors (P2X7R), and exposure to ATP led to high-frequency spiking, irreversible increases in cytosolic calcium and cell death. To assess the potential effect of P2X7R blockade in ameliorating acute spinal cord injury (SCI), we delivered P2X7R antagonists OxATP or PPADS to rats after acute impact injury. We found that both OxATP and PPADS significantly improved functional recovery and diminished cell death in the peritraumatic zone. These observations demonstrate that SCI is associated with prolonged purinergic receptor activation, which results in excitotoxicity-based neuronal degeneration. P2X7R antagonists inhibit this process, reducing both the histological extent and functional sequelae of acute SCI.