A função do anti-RAGE na barreira hematoencefálica e função cognitiva na investigação da meningite bacteriana como fator de risco para doença do Alzheimer

Artigo apresentado como requisito parcial para obtenção do grau de Bacharel, no Curso de Medicina, da Universidade do Extremo Sul Catarinense- UNESCA meningite bacteriana é uma infecção do sistema nervoso central associada a distúrbios neurológicos. Estudos sugerem uma via fisiopatológica em comum entre meningite bacteriana e neurodegeneração que, pela neuroinflamação, pode levar ao desenvolvimento da doença de Alzheimer pelo início da cascata de sinalização do RAGE, aumentando a deposição de β amilóide. Assim, a inibição de RAGE pode ser uma ferramenta terapêutica na prevenção da neurodegeneração causada por infecções. Esse estudo investigou a função do anti-RAGE na integridade da barreira hematoencefálica (BHE) e cognição em modelo animal de meningite pneumocócica. Ratos Wistar machos adultos receberam líquido cefalorraquidiano artificial ou suspensão de Streptococcus pneumoniae. Os animais foram divididos em grupo controle/salina, controle/anti-RAGE, meningite/salina e meningite/anti-RAGE. Para avaliação da integridade da BHE receberam tratamento com salina ou anti-RAGE (1.5 mg/kg) imediatamente após a inoculação, foram mortos em 12, 18 e 24 horas após a indução. Para os testes comportamentais, 18 horas após a indução receberam ceftriaxona a cada 12h/7 dias. O tratamento com anti-RAGE iniciou em 18 horas até o 5o dia após a indução, 1 vez ao dia. Dez dias após a inoculação bacteriana foram submetidos aos testes de habituação ao campo aberto e reconhecimento de objetos novos. Os animais tratados com anti-RAGE tiveram prevenção da quebra da BHE. Em ambos testes comportamentais houve prevenção de prejuizo de memória no grupo meningite/anti-RAGE comparado aos que receberam salina. Nossos resultados sugerem que o anti-RAGE pode atuar na prevenção de danos causados pela neuroinflamação, apoiando a meningite bacteriana como fator de risco para neurodegeneração

Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis

Objective: To evaluate the influence of environmental enrichment (EE) on memory, cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. Methods: On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 × 106 CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood). EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. Results: The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. Conclusions: The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis

Cardiovascular Outcomes of Sodium-Glucose Cotransporter-2 Inhibitors Therapy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Updated Meta-Analysis

BACKGROUND AND OBJECTIVESThe efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).METHODSThis systematic review and updated meta-analysis of randomized controlled trials (RCTs) compared cardiovascular outcomes of patients with T2DM and CKD treated with SGLT2i to placebo. PubMed, Embase, and Cochrane were systematically searched. Prespecified subgroup analyses were performed in strata of estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m² and 45 to 59 mL/min/1.73 m².RESULTSNine RCTs comprising 29,146 patients were selected. Average follow-up ranged from 0.75 to 4.2 years. SGLT2i were shown to reduce the risk of all-cause mortality (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97; p=0.01), the composite of cardiovascular mortality or hospitalizations for heart failure (HHF: HR, 0.71; 95% CI, 0.65-0.78; p<0.001), cardiovascular mortality (HR, 0.86; 95% CI, 0.76-0.98; p=0.02), HHF (HR, 0.62; 95% CI, 0.55-0.71; p<0.001), major adverse cardiovascular events (HR, 0.85; 95% CI, 0.77-0.94; p=0.002), stroke (HR, 0.76; 95% CI, 0.59-0.97; p=0.03), and myocardial infarction (HR, 0.78; 95% CI, 0.67-0.91; p=0.001). These findings were consistent over strata of eGFR, albeit with a lower incidence of stroke in patients treated with SGLT2i with eGFR <45 mL/min/1.73 m² (p-value for interaction=0.04).CONCLUSIONSCompared with a placebo, patients with T2DM and CKD treated with SGLT2i experience a reduction in all-cause mortality, cardiovascular mortality, and HHF.TRIAL REGISTRATIONPROSPERO Identifier: CRD42023401081

Resumos concluídos - Medicina

Resumos concluídos - Medicin

Resumos concluídos - Neurociências

Resumos concluídos - Neurociência