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1.
Crit Care ; 25(1): 236, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229735

RESUMO

Infectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood-brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation.


Assuntos
Encefalopatias/imunologia , COVID-19/complicações , Citocinas/imunologia , Influenza Humana/complicações , Malária/complicações , Sepse/complicações , Barreira Hematoencefálica/imunologia , Encefalopatias/prevenção & controle , COVID-19/imunologia , Humanos , Influenza Humana/imunologia , Malária/imunologia , Sepse/imunologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-34135107

RESUMO

OBJECTIVE: Coronavirus disease (COVID-19) has been associated with a large variety of neurologic disorders. However, the mechanisms underlying these neurologic complications remain elusive. In this study, we aimed at determining whether neurologic symptoms were caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) direct infection or by either systemic or local proinflammatory mediators. METHODS: In this cross-sectional study, we checked for SARS-CoV-2 RNA by quantitative reverse transcription PCR, SARS-CoV-2-specific antibodies, and 49 cytokines/chemokines/growth factors (by Luminex) in the CSF +/- sera of a cohort of 22 COVID-19 patients with neurologic presentation and 55 neurologic control patients (inflammatory neurologic disorder [IND], noninflammatory neurologic disorder, and MS). RESULTS: We detected anti-SARS-CoV-2 immunoglobulin G in patients with severe COVID-19 with signs of intrathecal synthesis for some of them. Of the 4 categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines, and growth factors. By contrast, patients with COVID-19 did not present overall upregulation of inflammatory mediators in the CSF. However, patients with severe COVID-19 (intensive care unit patients) exhibited higher concentrations of CCL2, CXCL8, and vascular endothelium growth factor A (VEGF-A) in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated albumin ratio and correlated with the increase of peripheral inflammation (serum hepatocyte growth factor [HGF] and CXCL10). CONCLUSIONS: Our results do not indicate active replication of SARS-CoV-2 in the CSF or signs of massive inflammation in the CSF compartment but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.


Assuntos
Encefalopatias/etiologia , COVID-19/complicações , Citocinas/líquido cefalorraquidiano , Inflamação/etiologia , Acoplamento Neurovascular , SARS-CoV-2/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/líquido cefalorraquidiano , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/imunologia , Encefalopatias/fisiopatologia , COVID-19/líquido cefalorraquidiano , COVID-19/imunologia , Cuidados Críticos , Estudos Transversais , Citocinas/sangue , Eletroencefalografia , Feminino , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Inflamação/líquido cefalorraquidiano , Inflamação/imunologia , Interleucina-8/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Acoplamento Neurovascular/imunologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Adulto Jovem
3.
J Neuroimmunol ; 356: 577597, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33964735

RESUMO

We enumerated conventional and innate lymphocyte populations in neonates with neonatal encephalopathy (NE), school-age children post-NE, children with cerebral palsy and age-matched controls. Using flow cytometry, we demonstrate alterations in circulating T, B and natural killer cell numbers. Invariant natural killer T cell and Vδ2+ γδ T cell numbers and frequencies were strikingly higher in neonates with NE, children post-NE and children with cerebral palsy compared to age-matched controls, whereas mucosal-associated invariant T cells and Vδ1 T cells were depleted from children with cerebral palsy. Upon stimulation ex vivo, T cells, natural killer cells and Vδ2 T cells from neonates with NE more readily produced inflammatory cytokines than their counterparts from healthy neonates, suggesting that they were previously primed or activated. Thus, innate and conventional lymphocytes are numerically and functionally altered in neonates with NE and these changes may persist into school-age.


Assuntos
Encefalopatias/sangue , Encefalopatias/diagnóstico , Paralisia Cerebral/sangue , Paralisia Cerebral/diagnóstico , Células T Matadoras Naturais/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/sangue , Encefalopatias/imunologia , Paralisia Cerebral/imunologia , Criança , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Células T Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Estudantes , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
4.
Diagn Pathol ; 16(1): 34, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882979

RESUMO

INTRODUCTION: Rhinocerebral mucormycosis is a rare and severe form of opportunistic fungal infection that can develop rapidly and cause significant mortality, particularly among diabetic patients suffering from ketoacidosis. Diagnosing rhinocerebral mucormycosis during the early stages of infection is challenging. CASE PRESENTATION: We describe a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis. In this case, the condition was not diagnosed during the optimal treatment window. we therefore provide a thorough overview of related clinical findings and histopathological characteristics, and we discuss potential differential diagnoses. CONCLUSIONS: In summary, we described a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis, with the optimal treatment window for this condition having been missed. This report suggests that a definitive mucormycosis diagnosis can be made based upon tissue biopsy that reveals the presence of characteristic hyphae. Early diagnosis and treatment are essential in order to improve patient prognosis.


Assuntos
Cetoacidose Diabética/complicações , Hospedeiro Imunocomprometido , Mucormicose/patologia , Infecções Oportunistas/patologia , Pancreatite/complicações , Adulto , Encefalopatias/imunologia , Encefalopatias/microbiologia , Encefalopatias/patologia , Evolução Fatal , Humanos , Masculino , Mucormicose/diagnóstico , Mucormicose/imunologia , Doenças Nasais/imunologia , Doenças Nasais/microbiologia , Doenças Nasais/patologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia
5.
Clin Exp Immunol ; 205(1): 89-97, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33768526

RESUMO

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1ß, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1ß and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1ß gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.


Assuntos
Encefalopatias/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Criança , Pré-Escolar , Citocinas/imunologia , Feminino , Humanos , Recém-Nascido , Interleucina-1beta/imunologia , Lipopolissacarídeos/imunologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Regulação para Cima/imunologia
6.
Int J Mol Sci ; 22(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673426

RESUMO

During persistent human beta-herpesvirus (HHV) infection, clinical manifestations may not appear. However, the lifelong influence of HHV is often associated with pathological changes in the central nervous system. Herein, we evaluated possible associations between immunoexpression of HHV-6, -7, and cellular immune response across different brain regions. The study aimed to explore HHV-6, -7 infection within the cortical lobes in cases of unspecified encephalopathy (UEP) and nonpathological conditions. We confirmed the presence of viral DNA by nPCR and viral antigens by immunohistochemistry. Overall, we have shown a significant increase (p < 0.001) of HHV antigen expression, especially HHV-7 in the temporal gray matter. Although HHV-infected neurons were found notably in the case of HHV-7, our observations suggest that higher (p < 0.001) cell tropism is associated with glial and endothelial cells in both UEP group and controls. HHV-6, predominantly detected in oligodendrocytes (p < 0.001), and HHV-7, predominantly detected in both astrocytes and oligodendrocytes (p < 0.001), exhibit varying effects on neural homeostasis. This indicates a high number (p < 0.001) of activated microglia observed in the temporal lobe in the UEP group. The question remains of whether human HHV contributes to neurological diseases or are markers for some aspect of the disease process.


Assuntos
Encefalopatias/imunologia , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Imunidade Celular , Neuroglia/virologia , Infecções por Roseolovirus/imunologia , Adulto , Idoso , Antígenos Virais/análise , Astrócitos/virologia , Encéfalo/imunologia , Encéfalo/virologia , Encefalopatias/virologia , Células Endoteliais/virologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Oligodendroglia/virologia
8.
Pharmacol Res ; 168: 105581, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33781873

RESUMO

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches.


Assuntos
Encefalopatias/terapia , Encéfalo/efeitos dos fármacos , COVID-19/terapia , Cardiopatias/terapia , Coração/efeitos dos fármacos , Corticosteroides/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Encéfalo/imunologia , Encéfalo/metabolismo , Encefalopatias/imunologia , Encefalopatias/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , Cuidados Críticos/métodos , Estado Terminal/terapia , Suplementos Nutricionais , Alimento Funcional , Cardiopatias/imunologia , Cardiopatias/metabolismo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/imunologia , Microvasos/metabolismo , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/terapia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo
9.
BMC Neurol ; 21(1): 85, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618681

RESUMO

BACKGROUND: The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. CASE PRESENTATION: Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. CONCLUSION: This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.


Assuntos
Analgésicos Opioides/envenenamento , Ataxia/induzido quimicamente , Encefalopatias/induzido quimicamente , Disfunção Cognitiva/induzido quimicamente , Perda Auditiva Bilateral/induzido quimicamente , Metadona/envenenamento , Paraparesia/induzido quimicamente , Abuso de Substâncias por Via Intravenosa , Administração Intravenosa , Ataxia/fisiopatologia , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Encefalopatias/imunologia , Encefalopatias/fisiopatologia , Edema Encefálico/induzido quimicamente , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/imunologia , Edema Encefálico/fisiopatologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Perda Auditiva Bilateral/fisiopatologia , Humanos , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Imageamento por Ressonância Magnética , Masculino , Monócitos/imunologia , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/fisiopatologia , Paraparesia/fisiopatologia , Adulto Jovem
10.
Neurol Sci ; 42(2): 479-489, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33409828

RESUMO

OBJECTIVE: To describe the clinical, neurological, neuroimaging, and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center. METHODS: We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020. RESULTS: Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate, and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series, the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2), or severe (3), p < 0.001). CONCLUSION: In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.


Assuntos
Encefalopatias/etiologia , COVID-19/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/diagnóstico por imagem , Encefalopatias/imunologia , COVID-19/mortalidade , COVID-19/terapia , Feminino , Mortalidade Hospitalar , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária
11.
World Neurosurg ; 145: e149-e154, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010505

RESUMO

BACKGROUND: Central nervous system involvement is commonly seen in patients with human immunodeficiency virus (HIV) infection, with up to 2%-10% of patients presenting with intracranial mass lesions. The management of these lesions depends largely on their etiology and their relative frequency in the local population. METHODS: We performed a retrospective chart review of patients with HIV and evidence of intracranial mass lesions on cranial magnetic resonance imaging or computed tomography from 2007 to 2018. Demographic data, clinical features, etiology, surgical management, and outcomes were collected. RESULTS: The prevalence of intracranial mass lesions in our cohort was 2.2% (45/2032). Patients were predominantly male (98%), with a mean age at diagnosis of 28 years. The most common clinical manifestations were headache (75%), focal weakness (49%), and seizures (32%). The most common diagnoses were toxoplasmic encephalitis (51%) and tuberculosis (24%). Biopsy or excision was performed in 10% of cases, leading to a definitive diagnosis in 60% of these cases. A favorable outcome was observed in 58% of all patients at 46 months median follow-up, with adequate disease-specific treatment. CONCLUSIONS: The prevalence of intracranial mass lesions in Filipino patients with HIV is 2.2%. The most common etiology was toxoplasmic encephalitis followed by tuberculosis. These findings are substantially different from other findings reported in the literature and should be considered in formulating guidelines for the Filipino population.


Assuntos
Encefalopatias/epidemiologia , Encefalopatias/imunologia , Infecções por HIV/complicações , Hospedeiro Imunocomprometido , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Filipinas , Prevalência , Estudos Retrospectivos
12.
Front Immunol ; 11: 604179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362788

RESUMO

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1ß and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.


Assuntos
Bactérias/metabolismo , Encefalopatias/microbiologia , Encéfalo/metabolismo , Microbioma Gastrointestinal , Inflamassomos/metabolismo , Intestinos/microbiologia , Transtornos Mentais/microbiologia , Animais , Bactérias/imunologia , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Encefalopatias/imunologia , Encefalopatias/metabolismo , Encefalopatias/fisiopatologia , Disbiose , Interações Hospedeiro-Patógeno , Humanos , Inflamassomos/imunologia , Intestinos/imunologia , Intestinos/inervação , Transtornos Mentais/imunologia , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia
13.
Biol Pharm Bull ; 43(11): 1669-1677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132311

RESUMO

Prostaglandin (PG) D2 is a lipid mediator, and in the brain, overproduction of PGD2 is reportedly involved in the progression and exacerbation of neuroinflammation. The objective of this study was to elucidate PGD2 efflux transport, under normal and inflammatory conditions, across the blood-brain barrier (BBB), which is formed by brain capillaries. Elimination of [3H]PGD2 across the BBB of normal and lipopolysaccharide (LPS)-induced inflammatory rats was examined by the intracerebral microinjection technique. After intracerebral injection, the percentage of [3H]PGD2 remaining in the ipsilateral cerebrum decreased with time, with a half-life of 13 min. This [3H]PGD2 elimination across the BBB was significantly inhibited by the co-administration of unlabeled PGD2, which suggests carrier-mediated PGD2 efflux transport at the BBB. In isolated rat brain capillaries, mRNA expression of organic anion transporter (Oat) 3, organic anion-transporting polypeptide (Oatp) 1a4, and multidrug resistance-associated protein (Mrp) 4 was observed. In addition, co-administration of substrates/inhibitors for Oat3, Oatp1a4, and/or Mrp4, such as benzylpenicillin and cefmetazole, reduced [3H]PGD2 elimination across the BBB. Data suggest that Oat3 and Mrp4, but not Oatp1a4 are involved in PGD2 elimination across the BBB, as Oatp1a4-expressing Xenopus (X.) oocytes did not show the significant [3H]PGD2 uptake compared with water-injected X. oocytes. In LPS-treated rats, [3H]PGD2 elimination across the BBB and mRNA expression levels of Oat3 and Mrp4 were significantly decreased. Our data suggest that Oat3- and Mrp4-mediated PGD2 elimination across the BBB is attenuated under inflammatory conditions.


Assuntos
Barreira Hematoencefálica/patologia , Encefalopatias/imunologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Prostaglandina D2/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/imunologia , Encefalopatias/patologia , Cefmetazol/administração & dosagem , Modelos Animais de Doenças , Regulação para Baixo/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Masculino , Microinjeções , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Oócitos , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Penicilina G/administração & dosagem , Ratos , Xenopus laevis
14.
Fluids Barriers CNS ; 17(1): 69, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208141

RESUMO

The blood-brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain's metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain-blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.


Assuntos
Transporte Biológico/fisiologia , Biomarcadores , Barreira Hematoencefálica/anatomia & histologia , Barreira Hematoencefálica/fisiologia , Encefalopatias , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/metabolismo , Encefalopatias/imunologia , Encefalopatias/metabolismo , Encefalopatias/fisiopatologia , Humanos
15.
J Neuroimmunol ; 349: 577400, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032013

RESUMO

Encephalopathy is emerging as a recurrent complication of COVID-19 yet remains poorly characterized. We report the case of a middle-aged woman with COVID-19-related encephalopathy presenting as expressive aphasia and inattentiveness, subsequently progressing to agitation and marked confusion. Brain MRI and CSF analysis were unremarkable, while EEG showed slowing with frontal sharp waves. Neuropsychiatric symptoms resolved following treatment with tocilizumab. CNS involvement in COVID-19 may present as a subacute encephalopathy characterized by prominent frontal lobe dysfunction, with language disturbances as first neurological manifestation. Future studies should further investigate the role of tocilizumab in treating COVID-19-related encephalopathy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Afasia/etiologia , Encefalopatias/virologia , COVID-19/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Encefalopatias/tratamento farmacológico , Encefalopatias/imunologia , COVID-19/tratamento farmacológico , COVID-19/imunologia , Síndrome da Liberação de Citocina/virologia , Feminino , Humanos , Pessoa de Meia-Idade , SARS-CoV-2
17.
J Neurovirol ; 26(5): 631-641, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876900

RESUMO

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.


Assuntos
Betacoronavirus/patogenicidade , Encefalopatias/complicações , Infecções por Coronavirus/complicações , Transtornos do Olfato/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Acidente Vascular Cerebral/complicações , Enzima de Conversão de Angiotensina 2 , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/virologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalopatias/virologia , Efeito Espectador , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/imunologia , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Embolia Pulmonar/imunologia , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , SARS-CoV-2 , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia
18.
Indian J Tuberc ; 67(3): 286-294, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32825855

RESUMO

CONTEXT: Intracranial tuberculomas are rare yet lethal forms of tuberculosis. Diagnosis is often difficult because of its nonspecific symptoms and radiological findings. AIM: This study aims to perform a literature review of multiple tuberculomas to improve disease recognition and management in immunocompetent patients along with presenting a case report on the topic. DATA SOURCES: Scopus, LILACS, Ovid MEDLINE and EMBASE. STUDY SELECTION: Case reports and case series up to December 2018 in English, Spanish, and Portuguese focusing on intracranial tuberculomas in adult and pediatric immunocompetent patients. Data on presentation, diagnostic workup, and treatment was analyzed. DATA EXTRACTION: Cochrane Collaboration/Cochrane Handbook and PRISMA guidelines. RESULTS: Twenty reports involving 21 patients were included. Most patients were male (57.14%). The average age at diagnosis was 26.9 ± 14.9 years. Headache was the most common presenting symptom (52.4%; 11/21), followed by motor weakness (47.6%; 10/21) and vomiting (23.8%; 5/21). MRI was the most used image technique (17/21). Most lesions occurring in the cerebral hemispheres (16/21); we found five or more lesions in 66.6% (14/21) of the patients. The majority treated with anti-tuberculous drugs resulted in a favorable outcome. CONCLUSIONS: Immunocompetent patients living in TB endemic areas whose clinical evaluation and neuroimaging findings are compatible with tuberculoma should undergo anti-tubercular treatment despite a lack of bacteriological confirmation.


Assuntos
Antituberculosos/uso terapêutico , Encefalopatias/diagnóstico por imagem , Glucocorticoides/uso terapêutico , Tuberculoma Intracraniano/diagnóstico por imagem , Tuberculose Pulmonar/diagnóstico por imagem , Cegueira/fisiopatologia , Encéfalo/diagnóstico por imagem , Encefalopatias/tratamento farmacológico , Encefalopatias/imunologia , Encefalopatias/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Dexametasona/uso terapêutico , Quimioterapia Combinada , Doenças Endêmicas , Etambutol/uso terapêutico , Feminino , Humanos , Imunocompetência , Isoniazida/uso terapêutico , Imageamento por Ressonância Magnética , Náusea/fisiopatologia , Nistagmo Patológico/fisiopatologia , Peru , Pirazinamida/uso terapêutico , Quadriplegia/fisiopatologia , Rifampina/uso terapêutico , Tomografia Computadorizada por Raios X , Tuberculoma Intracraniano/tratamento farmacológico , Tuberculoma Intracraniano/imunologia , Tuberculoma Intracraniano/fisiopatologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/imunologia , Vômito/fisiopatologia , Adulto Jovem
19.
Curr Opin Microbiol ; 58: 41-46, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32828989

RESUMO

As the incidence rate of invasive fungal infections has increased with the use of modern medical interventions, so too has the occurrence of fungi invading the brain. Fungi such as Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus often infect immunocompromised individuals, and can use several strategies to invade the central nervous system (CNS) by penetrating the blood-brain barrier. Once in the brain parenchyma the specialized resident immune cells need to effectively recognize the fungus and mount an appropriate immune response to clear the infection, without causing debilitating immune-mediated toxicity and neuronal damage. Here we review the current knowledge pertaining to the antifungal response of the CNS and highlight areas where future research is required.


Assuntos
Encéfalo/imunologia , Fungos/fisiologia , Infecções Fúngicas Invasivas/imunologia , Animais , Encefalopatias/imunologia , Encefalopatias/microbiologia , Fungos/genética , Humanos , Imunidade , Infecções Fúngicas Invasivas/microbiologia
20.
J Neurovirol ; 26(5): 785-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666422

RESUMO

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR-confirmed SARS-CoV-2-infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.


Assuntos
Ageusia/complicações , Betacoronavirus/patogenicidade , Encefalopatias/complicações , Infecções por Coronavirus/complicações , Cefaleia/complicações , Transtornos do Olfato/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Ageusia/imunologia , Ageusia/patologia , Ageusia/virologia , Encéfalo/patologia , Encéfalo/virologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalopatias/virologia , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Europa (Continente) , Feminino , Cefaleia/imunologia , Cefaleia/patologia , Cefaleia/virologia , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Transtornos do Olfato/imunologia , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SARS-CoV-2 , América do Sul , Fatores de Tempo
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