Neuroprotective effect of ischemic preconditioning via modulating the expression of adropin and oxidative markers against transient cerebral ischemia in diabetic rats
Introduction
Ischemic preconditioning (IPreC) is the appearance of the earlier stress response that occurs during repeated episodes of brief ischemia and reperfusion and can restore the brain to tolerant a potential lethal ischemic injury [1], [2], [3]. Short episodes of IPreC stimuli may imitate some of the characteristics of clinical transient ischemic attacks (TIAs). A TIA occurring before a stroke could lead to a reduced severity of a subsequent stroke [5].
Diabetes is an independent risk factor for stroke and contributes to the atherosclerotic process [6]. Hyperglycemia has been shown to increase the size of ischemic infarct and worsen the clinical outcome following a stroke [7]. Experimental data have suggested that chronic high blood glucose levels exacerbate oxidative stress [8], [9], [10]. Increased free radical formation together with a reduced antioxidant defense causes oxidative stress and may play a major role in precipitating both atherosclerotic and diabetic vascular disease and stroke-associated neuronal injury [9], [10], [11]. High plasma concentrations of antioxidants have been evaluated as neuroprotective agents in stroke [8], [12], [13]. Measurement of total oxidant status (TOS) and total antioxidant status (TAS) in body fluid is believed to be a useful biomarker to decide whether the antioxidants could protect against oxidative damage [13].
Recent data point out that adropin has a significant association with cardiovascular disease. The research has suggested that adropin, which is involved in modulation of insulin resistance and diabetes, may have a role to improve endothelial function, promote angiogenesis, and retard atherosclerosis [4], [14].
Based on these observations, the aim of the present study was to evaluate the neuroprotective mechanisms of IPreC on adropin and TAS-TOS levels in focal cerebral ischemia induced by transient middle cerebral artery occlusion in streptozotocin (STZ)-induced diabetic rat model and to explore the possible correlations between adropin, TAS-TOS and the ischemic infarct volumes in diabetic and non-diabetic rats. Also, we hypothesized that the adropin synthesized in the brain, could serve as a new biomarker for diagnosis of acute stroke, indeed adropin is possibly released by ischemic neurons into the bloodstream.
Section snippets
Animals
All animals were obtained from the Experimental Animal Research Laboratory at Bezmialem Vakif University, Istanbul, Turkey. Animals were allowed free access to food and water at controlled room temperature (22–25 °C) under a 12:12-h day/night cycle for the duration of the study. During the surgical procedures, body temperature was monitored using a Nimomed® infrared thermometer. All procedures were approved by the Animal Care and Use Committee at Bezmialem Vakif University and performed in
Mortality-morbidity
None of the animals died during the study period. After surgical procedures, carotid ligation did not cause any ptosis in the all animals, presumably the result of damage to the sympathetic nerve trunk during isolation of the carotid artery.
General characteristics of the study groups
The general characteristics of STZ-treated rats included reduced body weight and elevated blood glucose levels compared to non-diabetic ones. Statistically, no significant difference was observed in the initial values of plasma glucose levels when the study
Discussion
Ischemic preconditioning increases the durability of brain cells to ischemic insult due to involvement of the regulation of stress defense mechanisms [1], [2], [3]. In our study, we have established an intermittent left internal carotid artery occlusion as a preconditioning stimulus to induce early ischemic tolerance to transient focal cerebral ischemia.
Our data revealed that preconditioning significantly reduced the infarct size after cerebral ischemia and STZ-induced diabetes. Therefore to
Conclusion
In conclusion, ischemic preconditioning protected against focal ischemia in diabetic or non-diabetic rats. This protective model could offer an alternative research side for studying therapeutic strategies against stroke. The findings addressed the hypothesis that increased adropin levels inside the tissue after ischemic preconditioning might help to provide neuronal protection against ischemic brain injury. Concurrently, increased adropin in the blood stream could be a novel biomarker to
Acknowledgments
Institutional Review Board: None.
Ethics statement: Research Ethics Committee at Bezmialem Vakif University approved all described procedures.
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