Effect of Antioxidant Treatment in Global Ischemia and Ischemic Postconditioning in the Rat Hippocampus

Abstract

Ischemic postconditioning is a very effective way how to prevent delayed neuronal death. Effect of Ginkgo biloba extract (EGb 761; 40 mg/kg) posttreatment was studied on the rat model of transient forebrain ischemia and ischemia/postconditioning. Global ischemia was produced by four-vessel occlusion in Wistar male rats. Two experimental protocols were used: (a) 10 min of ischemia/7 days of reperfusion with or without EGb 761 treatment or (b) 10 min of ischemia/2 days of reperfusion/5 min of ischemia (postconditioning), following 5 days of reperfusion. EGb 761 was applied as follows: 30 min before 10 min of ischemia then 5 h, 1 and 2 days after 10 min of ischemia. Fluoro Jade B, marker for neuronal degeneration, was used for quantitative analysis of the most vulnerable hippocampal CA1 neurons. Cognitive and memory functions were tested by Morris water maze, as well. Administration of EGb 761 30 min before 10 min of ischemia or 5 h after ischemia has rather no protective effect on neuronal survival in CA1 region. Ten minutes of ischemia following ischemic postconditioning after 2 days of reperfusion trigger a significant neuroprotection of CA1 neurons, but it is abolished by EGb 761 posttreatment. Ischemia/postconditioning group showed a significant improvement of learning and memory on the seventh day of reperfusion. Protection of the most vulnerable CA1 neurons after ischemia/postconditioning is abolished by exogenous antioxidant treatment used in different time intervals after initial ischemia. Moreover, combination of EGb 761 administration with repeated stress (5 min ischemia used as postconditioning) causes cumulative injury of CA1 neurons.

Prosurvival NMDA 2A receptor signaling mediates postconditioning neuroprotection in the hippocampus

“…This same mechanism may underlie the Post C induction of NR2A phosphorylation observed in our study, as we have found that Post C rapidly enhances NADPH oxidase activity in the CA1 region and that administration of an NADPH oxidase inhibitor blocks Post C neuroprotection (Zhang G, Wang R, Brann D, unpublished observation). In support of this mechanism, Burda and coworkers (Domorakova et al, 2009), previously reported that administration of an antioxidant prevents Post C neuroprotection.…”

Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

“…Although our data do not allow us to delineate the mechanism by which this pre-conditioning is occurring, it may be mediated by an LCAR-dependent increase in anti-oxidant enzyme capacity. Studies have demonstrated that mild ischemia can upregulate SOD1, SOD2 and catalase in hippocampal tissue [29], [30]. Blocking this effect with an antisense to SOD1 significantly decreases the neuroprotective effect [31], [32], [33].…”

The effect of ischemic post-conditioning on hippocampal cell apoptosis following global brain ischemia in rats

“…These findings demonstrate the protective effect of ischemic post-conditioning and are consistent with findings from previous studies. [17][18][19] Both ischemic pre-conditioning (I PreC) and I PostC have protective effects against cerebral ischemia reperfusion injury. [20][21][22] However, I PreC is impractical as a clinical protective treatment because the onset of cerebral ischemia is unpredictable.…”