Stroke is a major public health problem, with high mortality rates, and a high frequency of disability. Between 1990 and 2010, stroke increased from the fifth to the third leading cause of disability. In addition, its incidence has increased among younger people, with severe health consequences and increased social costs. There is evidence that physical exercise promotes neuroprotective effects when used as a therapeutic treatment. However, the mechanisms of neuroprotection are not yet well known. The objective of the study was to evaluate the expression profile of microRNAs miR-16, miR-21 and miR-155 and the CASPASE-3 and Bcl-2 genes previously related to apoptosis in the tissue (ischemic focus). Forty-eight Wistar rats were divided into four experimental groups: control group, ischemia group, ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 19 (4): gmr18594 L.B. Porsani et al. 2 exercise group and exercise + ischemia group. Before the ischemic procedure, the animals in the exercise and exercise + ischemia groups were submitted to a treadmill training protocol for four weeks. The training lasted 30 min a day at a speed of 18 m / min. For real-time PCR analysis, a fragment of the ischemic area was collected from each animal using a punch to analyze the expression of miRNAs; miR16, miR-21, miR-155, CASPASE-3 and Bcl-2 genes. In the animals that had physical exercise, there appeared to be a neuroprotective effect by the action of microRNAs and CASPASE-3, although no significant difference was observed. Further studies are needed to elucidate the role of apoptosis mechanisms in cerebral ischemia associated with physical exercise, as well as the role of microRNAs in the modulation of targets associated with this mechanism.

Cerebral ischemia is one of the main causes of morbidity and mortality as Abusive use of alcohol also causes health problems, along with considerable social and economic repercussions. We examined how these two conditions affect histopathological signs, morphometrics, expression of apoptosisrelated proteins CASPASE 3 and BCL2, and serum gene expression of miRNA-21, in cerebral ischemia associated with a chronic alcoholism model in brain tissue (striatum, lateral and dorsolteral cortex). Fifty adult Wistar rats were divided into five groups: control (C), sham (S), ischemic (I), alcoholic (A) and ischemic/alcoholic ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 19 (4): gmr18624 D.C.P. Tirapelli et al. 2 groups (I+A). Brain samples were processed for histopathological, morphological, and immunohistochemical analyses for the expression of CASPASE 3 and BCL2, and blood was collected for analysis of miRNA-21 gene expression by real-time PCR. Histopathological changes such as neurons with pyknotic nuclei and diffuse neurons with loss of the contour of their cellular membranes and cytoplasmic edema, were observed in groups I and I+A in all three areas. Protein expression of CASPASE 3 was significantly higher than that of BCL2, with higher expression in groups I and I+A for these two proteins. Serum expression of miRNA-21 was low in all groups, and was slightly higher in groups I and I+A, with no significant differences. The histopathological and morphometric alterations, which were observed mainly in the ischemic animals, correlated with the expression of CASPASE 3. The expression of BCL2 was greater where histopathological changes and expression of CASPASE 3 were less evident. The I and I+A groups presented more histopathological changes, with greater neuronal loss and cerebral edema, and greater expression of CASPASE 3, suggesting that ischemia and alcoholism, when associated, can cause considerable injury and damage to brain tissue.