Abstract
Preconditioning of the brain by short-term ischemia increases brain tolerance to the subsequent severer ischemia. In this study, we investigated iron deposition in the cerebral cortex and the ischemic tolerance in a rat model of cerebral ischemia. Forebrain ischemia was induced by four-vessel occlusion for 5 min as ischemic preconditioning. Two days after preconditioning or after the sham-operation, the second ischemia was induced for 20 min. Changes in the cerebral cortex were examined after 1 to 8 weeks of recirculation following 20 min ischemia with or without preconditioning using the iron histochemistry. Granular deposits of the iron were found in the cytoplasm of the pyramidal cells in the layers III and V of the frontal cortex after 1 week of recirculation. When the rats were exposed to 5 min ischemia 2 days before 20 min lasting ischemia, the deposition of iron in the cytoplasm of the pyramidal cells in layers III and V of the frontal cortex was significantly lower during all periods of reperfusion. Preconditioning 5 min ischemia followed by 2 days of reperfusion before 20 min ischemia also prevented degeneration of the pyramidal neurons in layers III and V of the frontal cortex.
Highlights
Short periods of preconditioning by the ischemia can confer protection against injury which results from longer periods of focal or global ischemia in the central nervous system
Ischemic changes in neurons induced by transient forebrain ischemia were evaluated on sections of the frontal cortex stained with hematoxylin and eosin
The number of iron-containing pyramidal cells in the layer V of the frontal cortex increased in 1 week and reached maximal values after 8 weeks of recirculation (Figs. 1A, A’; C, C’; E, E’)
Summary
Short periods of preconditioning by the ischemia can confer protection against injury which results from longer periods of focal or global ischemia in the central nervous system. Since preconditioning harnesses robust endogenous protective potential of the tissue, elucidation of the mechanisms responsible for the induction of ischemic tolerance may have practical value in the search for effective means of therapeutic intervention in stroke. The recirculation of blood after transient ischemia causes an increase in low molecular weight species of iron, and free radicals formation initiated by iron leads to the brain damage by lipid peroxidation (11). Iron-induced hydroxyl radicals, lipid peroxidation and apoptotic cell death can be blocked by both, endogenously generated and exogenously administered nitric oxide. The ischemic preconditioning induces expression of stress proteins such as hemeoxygenase-1, neuronal nitric oxide synthase, redox factor-1 and inhibits p66shc, as well as hypothermia therapy suppresses the generation of toxic reactive oxygen, lipids and thiol species evoked by bioactive iron complexes in the brain (4)
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