Ischemic preconditioning in the rat hippocampus increases antioxidant activities but does not affect the level of hydroxyl radicals during subsequent severe ischemia

Abstract

Several studies have demonstrated that ischemic preconditioning increases superoxide dismutase activity, but it is unclear how ischemic preconditioning affects events downstream of hydrogen peroxide production during subsequent severe ischemia and reperfusion in the hippocampus. To answer this question, we investigated whether ischemic preconditioning in the hippocampal CA1 region increases the activities of antioxidant enzymes glutathione peroxidase and catalase, resulting in a decrease in the level of hydroxyl radicals during subsequent severe ischemia-reperfusion. Transient forebrain ischemia was induced by four-vessel occlusion in rats. Ischemic preconditioning for 3 min or a sham operation was performed and a 15-min severe ischemia was induced three days later. Ischemic preconditioning preserved the CA1 hippocampal neurons following severe ischemia. The concentration of 2,3-dihydroxybenzoic acid, an indicator of hydroxyl radical, was measured using in vivo microdialysis technique combined with HPLC. The ischemia-induced increase in the ratio of 2,3-dihydroxybenzoic acid concentration relative to baseline did not differ significantly between preconditioned and control groups. On the other hand, activities of the antioxidant enzymes glutathione peroxidase-1 and catalase were significantly increased at 3 days after ischemic preconditioning in the hippocampus. Our results suggest that, in preconditioned rats, while hydrogen peroxide is generated from severe ischemia, the activity of catalase and glutathione peroxidase-1 is correspondingly increased to eliminate the excessive hydrogen peroxide. However, our results show that the enhanced activity of these antioxidant enzymes in preconditioned rats is not sufficient to decrease hydroxyl radical levels during subsequent severe ischemia-reperfusion.

Activation of Nrf2-Regulated Glutathione Pathway Genes by Ischemic Preconditioning

“…Moreover, our finding that the gene expression of key markers of the glutathione pathway is increased following in vitro and in vivo preconditioning supports a neuroprotective role for the glutathione pathway in the Nrf2-dependent component of ischemic preconditioning. Indeed, numerous studies have identified glutathione as being involved in preconditioning [28, 29], and chemopreventive protection is associated with a marked upregulation of glutathione biosynthesis [16], as is Nrf2 activation in the brain [7, 15]. …”

Ischemic tolerance is associated with VEGF-C and VEGFR-3 signaling in the mouse hippocampus

“…Several cellular signaling pathways including the phosphatidylinositol 3-kinase (PI3K/Akt) and mitogenactivated protein kinase pathways are involved in the mechanisms of ischemic tolerance (Wick et al, 2002;Choi et al, 2007;Bhuiyan et al, 2011). The multifaceted protein kinase Akt inhibits programed cell death and enhances cell survival via regulating its many cytoplasmic targets such as Bcl-2-associated death promoter, glycogen synthase kinase-3b, procaspase-9 and cAMP response element-binding protein.…”

Research review on the pharmacological effects of astragalosideIV

“…The damage of CIRI is a two‐stage process: acute injuries and delayed injuries. The acute injuries occurred at an early stage, characterized by energy metabolism dysfunction, reactive oxygen species (ROS) accumulation , neurotoxicity of nitric oxide (NO) and excitatory amino acid (EAA), and the destruction of the blood–brain barrier (BBB). The delayed injuries happened in advanced stage during the period of the ischemia and reperfusion, characterized by the inflammatory response and apoptosis, which could aggravate the damage and extend the range of injuries.…”