O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico

Abstract

Considered one of the most common neurological diseases, stroke has a high morbidity and mortality, and corresponds to 85% of disease cases. Several factors are involved in disease etiology, such as changes in vascular permeability, oxidative stress, inflammation, apoptosis and DNA damage. Among the main consequences are cognitive and motor deficits, depending on the level and time of injury. The single nucleotide polymorphism Ala16Val (SNP) is a genetic mutation of the antioxidant enzyme superoxide dismutase and is associated with the risk factors of metabolic and vascular diseases, such as stroke. Brain derived neurotrophic (BDNF) is a neurotrofin that, among various functions, is associated with tissue regeneration after cerebrovascular lesions. Acetylcholine (ACh) is a neurotransmitter related to mnemonic processes, learning and motor functions. Thus, this study was to investigate the relationship between the polymorphism Ala16Val with oxidative, inflammatory, apoptotics and DNA damage markers, as well, with levels of BDNF, ACh, memory and functional capacity of chronic stroke patients. Fourthy-eight ischemic stroke patients with and fifthy healthy controls were subjected to questionnaires, laboratory tests and clinical trials. The results showed a higher proportion of the VV genotype in stroke patients compared to healthy individuals. VV genotype patients also showed higher levels of 2 -7 ′ ′ diclorofluorescein diacetate (DCFH-DA), nitrite/nitrate (NOX), tumor necrosis factor-α (TNF-α), acetylcholinesterase (AChE), caspase 8 (CASP 8), caspase 3 (CASP 3) and PicoGreen (PG), as well as decreased levels of BDNF and ACh. Similarly, in cognitive tests (working memory and total memory) and tests (Berg Balance scale and the senior fitness test-STF), VV genotype patients had worse results when compared with the other genotypes (stroke and control groups). In this way, the results suggest a relationship of polymorphism Ala16Val with oxidative/nitrosatve and inflammatory routes, culminated in activation of the apoptotic cascade and DNA damage, especially for VV genotype patients. Moreover, VV patients showed worst results in cognitive and motor tests, as well as low BDNF and ACh levels. Thus, is plausible to suggest that VV patients with present a worse performance in relation to cognitive and motor function, as well as increase in oxidative and inflammatory parameters. Our findings also related clinical changes reduced levels of BDNF and ACh, suggesting that knowledge of Mn-SOD polymorphism is important to evaluate the molecular mechanisms associated with neurovascular lesion and offer a individualized treatment for these patients.