Ischemic preconditioning reduces peripheral oxidative damage associated with brain ischemia in rats

Abstract

Brain ischemia followed by reperfusion causes neuronal death related to oxidative damage. Furthermore, it has been reported that subjects suffering from ischemic cerebrovascular disorders exhibit changes in circulating platelet aggregation, a characteristic that might be important for their clinical outcome. In the present investigation we studied tert-butyl hydroperoxide-initiated plasma chemiluminescence and thiol content as measures of peripheral oxidative damage in naive and preconditioned rats submitted to forebrain ischemia produced by the 4-vessel occlusion method. Rats were submitted to 2 or 10 min of global transient forebrain ischemia followed by 60 min or 1, 2, 5, 10 or 30 days of reperfusion. Preconditioned rats were submitted to a 10-min ischemic episode 1 day after a 2-min ischemic event (2 + 10 min), followed by 60 min or 1 or 2 days of reperfusion. It has been demonstrated that such preconditioning protects against neuronal death in rats and gerbils submitted to a lethal (10 min) ischemic episode. The results show that both 2 and 10 min of ischemia cause an increase of plasma chemiluminescence when compared to control and sham rats. In the 2-min ischemic group, the effect was not present after reperfusion. In the 10-min ischemic group, the increase was present up to 1 day after recirculation and values returned to control levels after 2 days. However, rats preconditioned to ischemia (2 + 10 min) and reperfusion showed no differences in plasma chemiluminescence when compared to controls. We also analyzed plasma thiol content since it has been described that sulfhydryl (SH) groups significantly contribute to the antioxidant capacity of plasma. There was a significant decrease of plasma thiol content after 2, 10 and 2 + 10 min of ischemia followed by reperfusion when compared to controls. We conclude that ischemia may cause, along with brain oxidative damage and cell death, a peripheral oxidative damage that is reduced by the preconditioning phenomenon.

Plasma low-molecular-weight thiol/disulphide homeostasis as an early indicator of global and focal cerebral ischaemia

“…The lack of correlation between the changes of thiols in plasma and brain in MCAO and BCAO suggests that different mechanisms are involved in the regulation of these redox systems. Previously, it was hypothesized that the main factor that contributes to reducing plasma SH is the formation of ROS in the brain tissue in the reperfusion phase [11]. However, it was later shown that endothelial dysfunction of peripheral vessels plays the leading role in the generalization of oxidative stress during cerebral ischaemia [6].…”

“…It has previously been shown that global cerebral ischaemia-reperfusion causes a rapid and continuous (up to 10-30 days) decrease in sulfhydryl (SH) groups and an increase in the products of lipid peroxidation in rat plasma [11]. Concomitantly, the total content of thiol groups may not reflect the full dynamics and intensity of oxidative stress, because of the contribution of albumin, which has a lifetime of about 20 days and an abnormally low pK (∼5) for its free SH group [12].…”

Time Course of Peripheral Oxidative Stress as Consequence of Global Ischaemic Brain Injury in Rats

“…We found that the TRAP values in plasma were significantly increased after 15 min of ischaemia, remained high at early (3 h) reperfusion and decreased significantly at the end of later (72 h) reperfusion. Indeed, recent studies have provided evidence that under pathologic conditions such as cerebral I/R, the antioxidant systems of plasma (Frassetto et al 1999) and brain have been changed (Hosseinzadeh and Sadeghnia 2005). Other studies demonstrated in different brain areas significantly decreased activities and levels of both non-enzymatic antioxidants like reduced glutathione (Nita et al 2001) and enzymatic antioxidants like superoxide dismutase (Aabdallah and Eid 2004), catalase (Homi et al 2002), glutathione reductase, glutathione-Stransferase and glutathione peroxidase (Ahmad et al 2006).…”