Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils

TL;DR

This study maps the timeline of oxidative damage across different brain regions in gerbils after transient ischemia, revealing region-specific patterns and potential windows for antioxidant therapy.

Contribution

It provides detailed temporal profiles of oxidative stress markers in hippocampus, cortex, and striatum post-ischemia, highlighting delayed hippocampal damage and early striatal changes.

Findings

Hippocampal oxidative damage peaks at 48-96 hours.

Striatal lipid peroxidation increases within 2 hours.

Cortex shows early oxidative changes without antioxidant impairment.

Abstract

The time course of oxidative damage in different brain regions was investigated in the gerbil model of transient cerebral ischemia. Animals were subjected to both common carotid arteries occlusion for 5 min. After the end of ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7 days), markers of lipid peroxidation, reduced and oxidized glutathione levels, glutathione peroxidase, glutathione reductase, manganese-dependent superoxide dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus was maximal at late stages after ischemia (48-96 h) coincident with a significant impairment in glutathione homeostasis. MnSOD increased in hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked reduction in the activity of glutathione-related enzymes. The late disturbance in oxidant-antioxidant balance corresponds with the time course of delayed neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early changes in oxidative damage with no significant impairment in antioxidant capacity. Striatal lipid peroxidation significantly increased as early as 2 h after ischemia and persisted until 48 h with respect to the sham-operated group. These results contribute significant information on the timing and factors that influence free radical formation following ischemic brain injury, an essential step in determining effective antioxidant intervention.