RESUMO
After an ischemic stroke, various harmful mechanisms contribute to tissue damage, including the inflammatory response. The increase in pro-inflammatory cytokines has been related to greater damage to the neural tissue and the promotion of neurological alterations, including cognitive impairment. Recent research has shown that the use of prebiotics and/or probiotics counteracts inflammation and improves cognitive function through the production of growth factors, such as brain-derived neurotrophic factor (BDNF), by reducing inflammatory molecules. Therefore, in this study, the effect of the symbiotic inulin and Enterococcus faecium on neuroprotection and memory improvement was evaluated in a rat model of transient middle cerebral artery occlusion (tMCAO). In order to accomplish this, the animals were subjected to ischemia; the experimental group was supplemented with the symbiotic and the control group with the vehicle. The neurological deficit as well as spatial and working memory were evaluated using the Zea Longa scale, Morris water maze, and the eight-arm maze tests, respectively. Infarct size, the levels of BDNF, and tumor necrosis factor-alpha (TNF-α) were also assessed. The results show that supplementation with the symbiotic significantly diminished the neurological deficit and infarct size, improved memory and learning, increased BDNF expression, and reduced TNF-α production. These findings provide new evidence about the therapeutic use of symbiotics for ischemic stroke and open up the possibilities for the design of further studies.
RESUMO
Regulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously. Thus, to determine whether Treg modulation mediated by statins can also be beneficial during stroke, cerebral ischemia was artificially induced in Wistar rats by transient middle cerebral artery occlusion (tMCAO) during 60 minutes with subsequent reperfusion for 7 days. Six hours after surgery, some animals were treated with atorvastatin (ATV, 10 mg/kg) or carboxymethylcellulose as vehicle at the same concentration every other day during 7 days. Some animals were sham operated as control group of surgery. Interestingly, ATV treatment prevented the development of infarct volume, reduced the neurological deficits, and the circulating and cervical lymph node CD25+FoxP3+ Treg population. Moreover, there was a reduction of glial cell activation, which correlated with decreased circulating Tregs. Remarkably, treatment with ATV induced an increase in the frequency of CD4+CD25+ T cells, in particular of those expressing CTLA-4, in brain samples. Together, these results suggest that ATV can modulate Tregs in peripheral tissue and favor their accumulation in the brain, where they can exert neuroprotective actions maybe by the reduction of glial cell activation.