RESUMO
Cryptococcosis, a globally distributed mycotic disease caused by Cryptococcus neoformans or C. gattii, has been extensively studied in various domestic animals and humans. However, non-domestic species have often been overlooked in the literature, with limited attention given to their susceptibility and contribution to the epidemiology of the disease. In this study, a captive two-year-old Cape hyrax in a Japanese zoo exhibited neurological symptoms and torticollis, ultimately succumbing to the infection. Necropsy and pathological analyses, including histopathological techniques and PCR, revealed the presence of C. neoformans in the lungs, cerebrum, and internal auditory canal. While cryptococcosis has been reported in various wild animals globally, this case represents the first documented cryptococcosis in Cape hyrax.
Assuntos
Animais de Zoológico , Criptococose , Cryptococcus neoformans , Animais , Cérebro/patologia , Cérebro/microbiologia , Criptococose/veterinária , Criptococose/patologia , Criptococose/microbiologia , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Evolução Fatal , Procaviídeos , Pulmão/patologia , Pulmão/microbiologiaRESUMO
OBJECTIVE: To investigate the relationship between neurocognitive deficits and structural changes on brain magnetic resonance imaging in people living with HIV (PLWH) with good virological control on combination antiretroviral therapy, compared with socioeconomically matched control participants recruited from the same communities. METHODS: Brain magnetic resonance imaging scans, and clinical and neuropsychological data were obtained from virologically controlled PLWH (viral load of <50 c/mL and at least 1 year of combination antiretroviral therapy) and socioeconomically matched control participants. Magnetic resonance imaging was carried out on 3 T scanner with 8-channel head coils and segmented using Classification using Derivative-based Features. Multiple regression analysis was performed to examine the association between brain volume and various clinical and neuropsychiatric parameters adjusting for age, race, and sex. To evaluate longitudinal changes in brain volumes, a random coefficient model was used to evaluate the changes over time (age) adjusting for sex and race. RESULTS: The cross-sectional study included 164 PLWH and 51 controls, and the longitudinal study included 68 PLWH and 20 controls with 2 or more visits (mean 2.2 years, range 0.8-5.1 years). Gray matter (GM) atrophy rate was significantly higher in PLWH compared with control participants, and importantly, the GM and global atrophy was associated with the various neuropsychological domain scores. Higher volume of white matter hyperintensities were associated with increased atherosclerotic cardiovascular disease risk score, and decreased executive functioning and memory domain scores in PLWH. INTERPRETATION: These findings suggest ongoing neurological damage even in virologically controlled participants, with significant implications for clinical management of PLWH. ANN NEUROL 2024;95:941-950.
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Substância Cinzenta , Infecções por HIV , Transtornos Neurocognitivos , Substância Branca , Humanos , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/patologia , Infecções por HIV/terapia , Transtornos Neurocognitivos/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Cérebro/diagnóstico por imagem , Cérebro/patologia , Estudos LongitudinaisRESUMO
Introduction: Cerebral radiation necrosis is rarely encountered in pediatric patients. This case report describes a child with cerebral radiation necrosis who was successfully treated using corticosteroids, bevacizumab, and hyperbaric oxygenation. Case report: A 3-year-old boy developed progressive extremity weakness six months after the completion of radiation therapy for the treatment of a neuroepithelial malignancy. Treatment with corticosteroids and bevacizumab was initiated, but his symptoms did not improve, and he was then referred for hyperbaric oxygen therapy. After completing 60 hyperbaric treatments, he experienced significant improvements in mobility, which remained stable over the next year. Discussion: Cerebral radiation necrosis typically presents in children with symptoms of ataxia or headache. Corticosteroids and bevacizumab are common treatments, but hyperbaric oxygen therapy has also been studied as a therapeutic modality for this condition. When considering the use of hyperbaric oxygenation in pediatric patients, careful attention to treatment planning and patient safety can reduce the risks of adverse events such as middle ear barotrauma and confinement anxiety. Conclusion: In addition to other available pharmacologic therapies, hyperbaric oxygenation should be considered for the treatment of pediatric patients with cerebral radiation necrosis.
Assuntos
Lesões Encefálicas , Cérebro , Oxigenoterapia Hiperbárica , Lesões por Radiação , Pré-Escolar , Humanos , Masculino , Barotrauma/etiologia , Barotrauma/prevenção & controle , Bevacizumab/uso terapêutico , Oxigenoterapia Hiperbárica/efeitos adversos , Oxigenoterapia Hiperbárica/métodos , Necrose/etiologia , Necrose/terapia , Cérebro/patologia , Cérebro/efeitos da radiação , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Lesões Encefálicas/terapia , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Lesões por Radiação/terapia , Neoplasias Neuroepiteliomatosas/radioterapiaRESUMO
PURPOSE: Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). METHODS: In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. RESULTS: In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. CONCLUSION: We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD.
Assuntos
Cérebro , Doença de Parkinson , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Tremor/diagnóstico por imagem , Tremor/patologia , Imagem de Tensor de Difusão , Encéfalo/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Cérebro/patologiaRESUMO
An 82-year-old woman had been suffering from progressive forgetfulness and abnormal speech and behavior for One month. Findings of the MRI of the head indicated scattered small cerebral infarcts in the cerebellum and in bilateral cerebral cortex/subcortical white matter. After admission, she experienced a subcortical hemorrhage, and the percentage of small cerebral infarcts increased over time. Based on the suspicion of central primary vasculitis or malignant lymphoma, we performed a brain biopsy targeting the right temporal lobe hemorrhage site, and the patient was diagnosed with cerebral amyloid angiopathy (CAA). We conclude that CAA can cause multiple small progressive cerebral infarcts.
Assuntos
Angiopatia Amiloide Cerebral , Cérebro , Substância Branca , Feminino , Humanos , Idoso de 80 Anos ou mais , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Infarto Cerebral/etiologia , Infarto Cerebral/complicações , Imageamento por Ressonância Magnética , Substância Branca/patologia , Cérebro/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Biópsia/efeitos adversosRESUMO
Astroblastomas are considered extremely rare tumors and have not been formally graded. While gene mutations are used to diagnose these tumors, further research is needed for proper diagnosis and classification. This report presents a case of astroblastoma in a 44-year-old woman. A tumor was found to have histology consistent with astroblastoma, with no MN1 gene changes. Several mutations were present, and fusion of the EWSR1 and EZHIP genes was noted, which has never been reported before in the literature. Fusions of the EWSR1 gene could be characteristics of astroblastomas, in addition to MN1 alterations, and identification of these mutations could help in the diagnosis of these rare tumors.
Assuntos
Neoplasias Encefálicas , Cérebro , Neoplasias Neuroepiteliomatosas , Feminino , Humanos , Adulto , Transativadores/genética , Neoplasias Neuroepiteliomatosas/patologia , Fatores de Transcrição/genética , Diagnóstico Diferencial , Cérebro/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Fusão Gênica , Proteína EWS de Ligação a RNA/genéticaRESUMO
Objective: To investigate clinicopathological features of multinodular and vacuolar neurodegenerative tumor (MVNT) of the cerebrum, and to investigate its immunophenotype, molecular characteristics and prognosis. Methods: Four cases were collected at the General Hospital of Southern Theater Command, Guangzhou, China and one case was collected at the First People's Hospital of Huizhou, China from 2013 to 2021. Clinical, histological, immunohistochemical and molecular characteristics of these five cases were analyzed. Follow-up was carried out to evaluate their prognoses. Results: There were four females and one male, with an average age of 42 years (range, 17 to 51 years). Four patients presented with seizures, while one presented with discomfort on the head. Pre-operative imaging demonstrated non-enhancing, T2-hyperintense multinodular lesions in the deep cortex and superficial white matter of the frontal (n=1) or temporal lobes (n=4). Microscopically, the tumor cells were mostly arranged in discrete and coalescent nodules primarily within the deep cortical ribbon and superficial subcortical white matter. The tumors were composed of large cells with ganglionic morphology, vesicular nuclei, prominent nucleoli and amphophilic or lightly basophilic cytoplasm. They exhibited varying degrees of matrix vacuolization. Vacuolated tumor cells did not show overt cellular atypia or any mitotic activities. Immunohistochemically, tumor cells exhibited widespread nuclear staining for the HuC/HuD neuronal antigens, SOX10 and Olig2. Expression of other neuronal markers, including synaptophysin, neurofilament and MAP2, was patchy to absent. The tumor cells were negative for NeuN, GFAP, p53, H3K27M, IDH1 R132H, ATRX, BRG1, INI1 and BRAF V600E. No aberrant molecular changes were identified in case 3 and case 5 using next-generation sequencing (including 131 genes related to diagnosis and prognosis of central nervous system tumors). All patients underwent complete or substantial tumor excision without adjuvant chemoradiotherapy. Post-operative follow-up information over intervals of 6 months to 8 years was available for five patients. All patients were free of recurrence. Conclusions: MVNT is an indolent tumor, mostly affecting adults, which supports classifying MVNT as WHO grade 1. There is no tumor recurrence even in the patients treated with subtotal surgical excision. MVNTs may be considered for observation or non-surgical treatments if they are asymptomatic.
Assuntos
Neoplasias Encefálicas , Cérebro , Adulto , Feminino , Humanos , Masculino , Neoplasias Encefálicas/patologia , Cérebro/metabolismo , Cérebro/patologia , Neurônios/metabolismo , Convulsões , Lobo Temporal/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
A male in his late 50s had been complaining of headaches and dizziness for 25 years. He also had episodes of losing consciousness, but had not sought treatment because of financial hardship. He was found in the ocean. Autopsy revealed foamy liquid leaking from his nose and mouth, and pleural effusions. The trachea and bronchi contained the same foamy liquid. The lungs were swollen and edematous, and leaked a large amount of foamy liquid. His cause of death was diagnosed as drowning. In the brain, the veins on the frontal lobe and the temporal pole, each on the right cerebral hemisphere, were dilated. A vascular lesion measuring 5 × 5 × 8 cm was found on the bottom of the right frontal lobe, and was located between the right middle cerebral artery and those veins. This vascular lesion extended to the brain parenchyma, and the basal ganglia of the right cerebrum was displaced outward and upward. The vascular lesions in the brain showed blood vessels of various sizes and shapes, and some of the vessel walls were thickened. The vascular lesion on the right frontal lobe was diagnosed as an arteriovenous malformation (AVM). According to the police investigation, the harbor where his body was found was a place he often came for fishing and walking. The possibility of suicide cannot be ruled out. Moreover, it was considered that his AVM might have rendered him unconscious, causing him to fall into the ocean.
Assuntos
Cérebro , Afogamento , Malformações Arteriovenosas Intracranianas , Humanos , Masculino , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/patologia , Malformações Arteriovenosas Intracranianas/terapia , Convulsões , Cérebro/patologia , Lobo FrontalRESUMO
Introduction Fluorescence guidance with 5-aminolevulinic acid (5-ALA) is a safe and reliable tool in total gross resection of intracranial tumors, especially malignant gliomas and cases of metastasis. In the present retrospective study, we have analyzed 5-ALA-induced fluorescence findings in different central nervous system (CNS) lesions to expand the indications of its use in differential diagnoses. Objectives To describe the indications and results of 5-ALA fluorescence in a series of 255 cases. Methods In 255 consecutive cases, we recorded age, gender, intraoperative 5-ALA fluorescence tumor response, and 5-ALA postresection status, as well the complications related to the method. Postresection was classified as '5-ALA free' or '5-ALA residual'. The diagnosis of histopathological tumor was established according to the current classification of the World Health Organization (WHO). Results There were 195 (76.4%) 5-ALA positive cases, 124 (63.5%) of whom underwent the '5-ALA free' resection. The findings in the positive cases were: 135 gliomas of all grades; 19 meningiomas; 4 hemangioblastomas; 1 solitary fibrous tumor; 27 metastases; 2 diffuse large B cell lymphomas; 2 cases of radionecrosis; 1 inflammatory disease; 2 cases of gliosis; 1 cysticercosis; and 1 immunoglobulin G4-related disease.
Assuntos
Neoplasias Encefálicas/cirurgia , Cirurgia Assistida por Computador/métodos , Ácido Aminolevulínico , Microscopia de Fluorescência/métodos , Cuidados Pós-Operatórios , Neoplasias Encefálicas/patologia , Cuidados Pré-Operatórios , Estudos Retrospectivos , Neuronavegação/métodos , Cérebro/cirurgia , Cérebro/patologia , Cuidados Intraoperatórios , América Latina/epidemiologiaRESUMO
BACKGROUND: Adult patients with moyamoya disease (MMD) occasionally exhibit cerebral hyperperfusion after arterial bypass surgery, leading to persistent cognitive decline. The present supplementary analysis of a prospective 5-year cohort study aimed to determine whether cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD causes cerebral atrophy, and whether the development of cerebral atrophy is related to persistent cognitive decline. METHODS: In total, 31 patients who underwent arterial bypass surgery also underwent fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and neuropsychological testing before surgery and at the end of a 5-year follow-up. The development of cerebral hyperperfusion and hyperperfusion syndrome after surgery was defined based on brain perfusion single-photon emission computed tomography (SPECT) findings and clinical symptoms. Univariate and multivariate logistic regression analyses of factors related to the development of cerebral atrophy on FLAIR MRI or cognitive decline on neuropsychological testing at the end of the 5-year follow-up were performed. RESULTS: Eleven patients (35%) developed cerebral atrophy in the frontal lobe where the superficial temporal artery was anastomosed. Cerebral hyperperfusion on brain perfusion SPECT (odds ratio [OR], 50.6; p = 0.0008) or cerebral hyperperfusion syndrome (OR, 41.8; p = 0.0026) was independently associated with the development of cerebral atrophy, and cerebral atrophy development was significantly associated with cognitive decline (OR, 47.7; p = 0.0010). CONCLUSIONS: Cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD can cause cerebral atrophy related to persistent cognitive decline.
Assuntos
Revascularização Cerebral , Doença de Moyamoya , Adulto , Atrofia/etiologia , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/métodos , Circulação Cerebrovascular , Cérebro/patologia , Estudos de Coortes , Humanos , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Alzheimer's disease (AD) is the most common age-associated dementia with complex pathological hallmarks. Mitochondrion, synaptosome, and myelin sheath appear to be vulnerable and play a key role in the pathogenesis of AD. To clarify the early mechanism associated with AD, followed by subcellular components separation, we performed iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics analysis to simultaneously investigate the differentially expressed proteins (DEPs) within the mitochondria, synaptosome, and myelin sheath in the cerebrum of the 6-month-old triple transgenic AD (3 × Tg-AD) and 6-month-old wild-type (WT) mice. A large number of DEPs between the AD and WT mice were identified. Most of them are related to mitochondria and synaptic dysfunction and cytoskeletal protein change. Differential expressions of Lrpprc, Nefl, and Sirpa were verified by Western blot analysis. The results suggest that decreased energy metabolism, impaired amino acid metabolism and neurotransmitter synthesis, increase compensatory fatty acid metabolism, up-regulated cytoskeletal protein expression, and oxidative stress are the early events of AD. Among these, mitochondrial damage, synaptic dysfunction, decreased energy metabolism, and abnormal amino acid metabolism are the most significant events. The results indicate that it is feasible to separate and simultaneously perform proteomics analysis on the three subcellular components.
Assuntos
Doença de Alzheimer , Cérebro , Doença de Alzheimer/patologia , Aminoácidos/metabolismo , Animais , Cérebro/metabolismo , Cérebro/patologia , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Bainha de Mielina/metabolismo , Proteômica/métodos , Sinaptossomos/metabolismoRESUMO
Glucocorticoids (GCs) regulate astrocyte function, while glutamine synthetase (GS), an enzyme highly expressed in astrocytes, is one of the most remarkable GCs-induced genes. GCs mediate their effects through their cognate glucocorticoid receptor (GRα and GRß isoforms); however, the mechanism via which these isoforms regulate GS activity in astrocytes remains unknown. We used dexamethasone (DEX), a classical GRα/GRß agonist, RU486, which is a specific GRß ligand, and Compound A, a known "dissociated" ligand, to delineate the mechanism via which GR modulates GS activity. Aged Mouse Cerebral Hemisphere astrocytes were treated with DEX (1 µM), RU486 (1 nM-1 µM) or compound A (10 µM), alone or in combination with DEX. GS activity and expression, GR isoforms (mRNA and protein levels), and GRα subcellular trafficking were measured. DEX increased GS activity in parallel with GRα nuclear translocation. RU486 increased GS activity in absence of GRα nuclear translocation implicating thus a role of GRß-mediated mechanism compound A had no effect on GS activity implicating a GRα-GRE-mediated mechanism. None of the compounds affected whole-cell GRα protein content. DEX reduced GRα and GRß mRNA levels, while RU486 increased GRß gene expression. We provide evidence that GS activity, in astrocytes, is regulated via GRα- and GRß-mediated pathways with important implications in pathological conditions in which astrocytes are involved.
Assuntos
Astrócitos/metabolismo , Cérebro/metabolismo , Glutamato-Amônia Ligase/metabolismo , Receptores de Glucocorticoides/metabolismo , Acetatos/farmacologia , Fatores Etários , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Astrócitos/efeitos dos fármacos , Células Cultivadas , Cérebro/efeitos dos fármacos , Cérebro/patologia , Dexametasona/farmacologia , Antagonistas de Hormônios/farmacologia , Camundongos , Mifepristona/farmacologia , Tiramina/análogos & derivados , Tiramina/farmacologiaRESUMO
Neurodevelopmental disorders are often caused by chromosomal microdeletions comprising numerous contiguous genes. A subset of neurofibromatosis type 1 (NF1) patients with severe developmental delays and intellectual disability harbors such a microdeletion event on chromosome 17q11.2, involving the NF1 gene and flanking regions (NF1 total gene deletion [NF1-TGD]). Using patient-derived human induced pluripotent stem cell (hiPSC)-forebrain cerebral organoids (hCOs), we identify both neural stem cell (NSC) proliferation and neuronal maturation abnormalities in NF1-TGD hCOs. While increased NSC proliferation results from decreased NF1/RAS regulation, the neuronal differentiation, survival, and maturation defects are caused by reduced cytokine receptor-like factor 3 (CRLF3) expression and impaired RhoA signaling. Furthermore, we demonstrate a higher autistic trait burden in NF1 patients harboring a deleterious germline mutation in the CRLF3 gene (c.1166T>C, p.Leu389Pro). Collectively, these findings identify a causative gene within the NF1-TGD locus responsible for hCO neuronal abnormalities and autism in children with NF1.
Assuntos
Cérebro/patologia , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Células-Tronco Pluripotentes Induzidas/patologia , Modelos Biológicos , Neurogênese/genética , Organoides/patologia , Receptores de Citocinas/metabolismo , Transtorno Autístico/genética , Linhagem Celular , Proliferação de Células , Dendritos/metabolismo , Dendritos/patologia , Ativação Enzimática , Deleção de Genes , Genes da Neurofibromatose 1 , Humanos , Mutação/genética , Transdução de Sinais , Proteínas ras/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Frontotemporal dementia (FTD) because of MAPT mutation causes pathological accumulation of tau and glutamatergic cortical neuronal death by unknown mechanisms. We used human induced pluripotent stem cell (iPSC)-derived cerebral organoids expressing tau-V337M and isogenic corrected controls to discover early alterations because of the mutation that precede neurodegeneration. At 2 months, mutant organoids show upregulated expression of MAPT, glutamatergic signaling pathways, and regulators, including the RNA-binding protein ELAVL4, and increased stress granules. Over the following 4 months, mutant organoids accumulate splicing changes, disruption of autophagy function, and build-up of tau and P-tau-S396. By 6 months, tau-V337M organoids show specific loss of glutamatergic neurons as seen in individuals with FTD. Mutant neurons are susceptible to glutamate toxicity, which can be rescued pharmacologically by the PIKFYVE kinase inhibitor apilimod. Our results demonstrate a sequence of events that precede neurodegeneration, revealing molecular pathways associated with glutamate signaling as potential targets for therapeutic intervention in FTD.
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Cérebro/patologia , Proteína Semelhante a ELAV 4/genética , Ácido Glutâmico/metabolismo , Mutação/genética , Neurônios/patologia , Organoides/metabolismo , Splicing de RNA/genética , Proteínas tau/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Biomarcadores/metabolismo , Padronização Corporal/efeitos dos fármacos , Padronização Corporal/genética , Morte Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Hidrazonas/farmacologia , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Morfolinas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Organoides/efeitos dos fármacos , Organoides/ultraestrutura , Fosforilação/efeitos dos fármacos , Pirimidinas/farmacologia , Splicing de RNA/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Grânulos de Estresse/efeitos dos fármacos , Grânulos de Estresse/metabolismo , Sinapses/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
Preterm infants often suffer from impaired postnatal brain development, and glutamate excitotoxicity is identified as a pivotal mechanism of hyperoxia-induced neurological abnormality. We aimed to investigate the effect of short time hyperoxia on glutamate homeostasis and glutamate transporters expressions in immature brain. Six-day-old (P6) rat pups were exposed to 80% oxygen for 24 h (the hyperoxia group) or placed in atmospheric air (the control group). The concentrations of glutamate and γ-aminobutyric acid (GABA) in immature cerebrum and cerebellum at P7, P14 and P21 were determined by ELISA. The mRNA levels of glutamate transporters including excitatory amino acid transporter 1 (EAAT1), EAAT2, EAAT3, vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 in brain were determined by qPCR. Glutamate accumulation was induced by hyperoxia both in immature cerebrum and cerebellum at P7 but got gradually attenuated at P14 and P21, as evidenced by the changes of glutamate and GABA concentrations. Hyperoxia also induced sustained glutamatic oxidative stress in both cerebrum and cerebellum, as GSH (reduced glutathione) levels in the hyperoxia group were constantly higher than the control group at three examined time-points. Furthermore, at P7, the expressions of all glutamate transporters decreased in both cerebrum and cerebellum except that of EAAT1. At P21, VGLUT2 in cerebrum and EAAT1, EAAT3 and VGLUT2 in cerebellum still displayed significant decrease in expression levels upon hyperoxia stimulation. Taken together, our results indicate that hyperoxia induces glutamate accumulation in brain of rat pups, which is associated with increased oxidative stress and decreased expressions of glutamate transporters.
Assuntos
Cerebelo/metabolismo , Cérebro/metabolismo , Hiperóxia/patologia , Doenças do Prematuro/patologia , Animais , Animais Recém-Nascidos , Cerebelo/crescimento & desenvolvimento , Cerebelo/patologia , Cérebro/crescimento & desenvolvimento , Cérebro/patologia , Modelos Animais de Doenças , Proteínas de Transporte de Glutamato da Membrana Plasmática/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Hiperóxia/etiologia , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido Prematuro/metabolismo , Doenças do Prematuro/etiologia , Masculino , Estresse Oxidativo , Oxigênio/administração & dosagem , Oxigênio/efeitos adversos , Ratos , Fatores de Tempo , Proteínas Vesiculares de Transporte de Glutamato/metabolismoAssuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cardiomiopatia Chagásica/patologia , Cérebro/patologia , Miocárdio/patologiaRESUMO
BACKGROUND AND PURPOSE: The association of perivascular spaces in the centrum semiovale with amyloid accumulation among patients with Alzheimer disease-related cognitive impairment is unknown. We evaluated this association in patients with Alzheimer disease-related cognitive impairment and ß-amyloid deposition, assessed with [18F] florbetaben PET/CT. MATERIALS AND METHODS: MR imaging and [18F] florbetaben PET/CT images of 144 patients with Alzheimer disease-related cognitive impairment were retrospectively evaluated. MR imaging-visible perivascular spaces were rated on a 4-point visual scale: a score of ≥3 or <3 indicated a high or low degree of MR imaging-visible perivascular spaces, respectively. Amyloid deposition was evaluated using the brain ß-amyloid plaque load scoring system. RESULTS: Compared with patients negative for ß-amyloid, those positive for it were older and more likely to have lower cognitive function, a diagnosis of Alzheimer disease, white matter hyperintensity, the Apolipoprotein E ε4 allele, and a high degree of MR imaging-visible perivascular spaces in the centrum semiovale. Multivariable analysis, adjusted for age and Apolipoprotein E status, revealed that a high degree of MR imaging-visible perivascular spaces in the centrum semiovale was independently associated with ß-amyloid positivity (odds ratio, 2.307; 95% CI, 1.036-5.136; P = .041). CONCLUSIONS: A high degree of MR imaging-visible perivascular spaces in the centrum semiovale independently predicted ß-amyloid positivity in patients with Alzheimer disease-related cognitive impairment. Thus, MR imaging-visible perivascular spaces in the centrum semiovale are associated with amyloid pathology of the brain and could be an indirect imaging marker of amyloid burden in patients with Alzheimer disease-related cognitive impairment.
Assuntos
Doença de Alzheimer , Cérebro/diagnóstico por imagem , Disfunção Cognitiva , Sistema Glinfático/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Cérebro/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Sistema Glinfático/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Placa Amiloide/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos RetrospectivosRESUMO
Individual-based morphological brain networks built from T1-weighted magnetic resonance imaging (MRI) reflect synchronous maturation intensities between anatomical regions at the individual level. Autism spectrum disorder (ASD) is a socio-cognitive and neurodevelopmental disorder with high neuroanatomical heterogeneity, but the specific patterns of morphological networks in ASD remain largely unexplored at the individual level. In this study, individual-based morphological networks were constructed by using high-resolution structural MRI data from 40 young children with ASD (age range: 2-8 years) and 38 age-, gender-, and handedness-matched typically developing children (TDC). Measurements were recorded as threefold. Results showed that compared with TDC, young children with ASD exhibited lower values of small-worldness (i.e., σ) of individual-level morphological brain networks, increased morphological connectivity in cortico-striatum-thalamic-cortical (CSTC) circuitry, and decreased morphological connectivity in the cortico-cortical network. In addition, morphological connectivity abnormalities can predict the severity of social communication deficits in young children with ASD, thus confirming an associational impact at the behavioral level. These findings suggest that the morphological brain network in the autistic developmental brain is inefficient in segregating and distributing information. The results also highlight the crucial role of abnormal morphological connectivity patterns in the socio-cognitive deficits of ASD and support the possible use of the aberrant developmental patterns of morphological brain networks in revealing new clinically-relevant biomarkers for ASD.
Assuntos
Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/fisiopatologia , Cérebro/patologia , Rede Nervosa/patologia , Tálamo/patologia , Transtorno do Espectro Autista/diagnóstico por imagem , Cérebro/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Tálamo/diagnóstico por imagemRESUMO
The brain is the major target of congenital cytomegalovirus (CMV) infection. It is possible that neuron disorder in the developing brain is a critical factor in the development of neuropsychiatric diseases in later life. Previous studies using mouse model of murine CMV (MCMV) infection demonstrated that the viral early antigen (E1 as a product of e1 gene) persists in the postnatal neurons of the hippocampus (HP) and cerebral cortex (CX) after the disappearance of lytic infection from non-neuronal cells in the periventricular (PV) region. Furthermore, neuron-specific activation of the MCMV-e1-promoter (e1-pro) was found in the cerebrum of transgenic mice carrying the e1-pro-lacZ reporter construct. In this study, in order to elucidate the mechanisms of e1-pro activation in cerebral neurons during actual MCMV infection, we have generated the recombinant MCMV (rMCMV) carrying long e1-pro1373- or short e1-pro448-EGFP reporter constructs. The length of the former, 1373 nucleotides (nt), is similar to that of transgenic mice. rMCMVs and wild type MCMV did not significantly differed in terms of viral replication or E1 expression. rMCMV-infected mouse embryonic fibroblasts showed lytic infection and activation of both promoters, while virus-infected cerebral neurons in primary neuronal cultures demonstrated the non-lytic and persistent infection as well as the activation of e1-pro-1373, but not -448. In the rMCMV-infected postnatal cerebrum, lytic infection and the activation of both promoters were found in non-neuronal cells of the PV region until postnatal 8 days (P8), but these disappeared at P12, while the activation of e1-pro-1373, but not -448 appeared in HP and CX neurons at P8 and were prolonged exclusively in these neurons at P12, with preservation of the neuronal morphology. Therefore, e1-pro-448 is sufficient to activate E1 expression in non-neuronal cells, however, the upstream sequence from nt -449 to -1373 in e1-pro-1373 is supposed to work as an enhancer necessary for the neuron-specific activation of e1-pro, particularly around the second postnatal week. This unique activation of e1-pro in developing cerebral neurons may be an important factor in the neurodevelopmental disorders induced by congenital CMV infection.