RESUMO
OBJECTIVE: To identify the role of changes in the expression of inflammation-related genes in cerebral microangiopathy/cerebral small vessel disease (cSVD). MATERIAL AND METHODS: Forty-four cSVD patients (mean age 61.4±9.2) and 11 controls (mean age 57.3±9.7) were studied. Gene expression was assessed on an individual NanoString nCounter panel of 58 inflammation-related genes and 4 reference genes. A set of genes was generated based on converging results of complete genome-wide association studies (GWAS) in cSVD and Alzheimer's disease (AD) and circulating markers associated with vascular wall and Brain lesions in cSVD. RNA was isolated from blood leukocytes and analyzed with the nCounter Analysis System, followed by analysis in nSolver 4.0. Results were verified by real-time PCR. RESULTS: CSVD patients had a significant decrease in BIN1 (log2FC=-1.272; p=0.039) and VEGFA (log2FC=-1.441; p=0.038) expression compared to controls, which showed predictive ability for cSVD. The cut-off for BIN1 expression was 5.76 a.u. (sensitivity 73%; specificity 75%) and the cut-off for VEGFA expression was 9.27 a.u. (sensitivity 64%; specificity 86%). Reduced expression of VEGFA (p=0.011), VEGFC (p=0.017), CD2AP (p=0.044) was associated with cognitive impairment (CI). There was a significant direct correlation between VEGFC expression and the scores on the Montreal Cognitive Assessment test and between BIN1 and VEGFC expression and delayed memory. CONCLUSION: The possible prediction of cSVD by reduced expression levels of BIN1, VEGFA and the association of clinically significant CI with reduced VEGFA and VEGFC expression indicate their importance in the development and progression of the disease. The established importance of these genes in the pathogenesis of AD suggests that similar changes in their expression profile in cSVD may be one of the conditions for the comorbidity of the two pathologies.
Assuntos
Doença de Alzheimer , Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Humanos , Pessoa de Meia-Idade , Idoso , Estudo de Associação Genômica Ampla , Doença de Alzheimer/genética , Doenças de Pequenos Vasos Cerebrais/genética , Disfunção Cognitiva/genética , Inflamação/genética , Expressão GênicaRESUMO
Over the past decade, non-invasive brain stimulation, in particular transcranial stimulation by direct electric current (TES), has been increasingly included in the array of methods used for rehabilitation of patients with post-stroke impairments (motor, speech, cognitive). Development of stimulation protocols with determination of the zones of exposure, as well as better understanding of the patterns of restoration of functional systems, became possible due to basic research using functional MRI paradigm. However, the complexity of the organization of the speech system, the variety of forms of aphasia that occur when it is damaged, the individual variability of neuroplastic processes, motivated a search for optimal stimulation protocols that contribute to the personification of the rehabilitation process. Portability, low cost of equipment, a good safety and tolerance profile, as well as a proven effect on neuroplasticity processes, are the undoubted advantages of TES-therapy. There is reason to believe that further study and clinical testing of this technique will turn it into the promising tool for enhancing the effectiveness of classical speech therapy approaches in patients with post-stroke aphasia.
