Abstract
Global cerebral ischemia (GCI) is one of the main causes of hippocampal neuronal death. Ischemic damage can be rescued by early blood reperfusion. However, under some circumstances reperfusion itself can trigger a cell death process that is initiated by the reintroduction of blood, followed by the production of superoxide, a blood–brain barrier (BBB) disruption and microglial activation. Protocatechuic acid (PCA) is a major metabolite of the antioxidant polyphenols, which have been discovered in green tea. PCA has been shown to have antioxidant effects on healthy cells and anti-proliferative effects on tumor cells. To test whether PCA can prevent ischemia-induced hippocampal neuronal death, rats were injected with PCA (30 mg/kg/day) per oral (p.o) for one week after global ischemia. To evaluate degenerating neurons, oxidative stress, microglial activation and BBB disruption, we performed Fluoro-Jade B (FJB), 4-hydroxynonenal (4HNE), CD11b, GFAP and IgG staining. In the present study, we found that PCA significantly decreased degenerating neuronal cell death, oxidative stress, microglial activation, astrocyte activation and BBB disruption compared with the vehicle-treated group after ischemia. In addition, an ischemia-induced reduction in glutathione (GSH) concentration in hippocampal neurons was recovered by PCA administration. Therefore, the administration of PCA may be further investigated as a promising tool for decreasing hippocampal neuronal death after global cerebral ischemia.
Highlights
Cerebrovascular disorders encompass a diverse range of neurological diseases, such as stroke, myocardial infarction, vascular dementia, and chronic cerebral hypoperfusion [1]
Ischemia-induced brain damage can be recovered via early reperfusion, but this reperfusion can, itself, become an initiation mechanism of a cell death pathway that is caused by blood reperfusion, blood–brain barrier (BBB) disruption, microglia activation and zinc release
We conducted NeuN staining in order to detect surviving neurons, and FJB (Fluoro-Jade B) staining in order to detect degenerating neurons in the hippocampal subiculum (Sub), the cornu ammonis 1 (CA1), the cornu ammonis 3 (CA3) and dentate gyrus (DG) area
Summary
Cerebrovascular disorders encompass a diverse range of neurological diseases, such as stroke, myocardial infarction, vascular dementia, and chronic cerebral hypoperfusion [1]. While focal ischemia can cause local damage and identify infarct volume, the advantage of global cerebral ischemia is that we can confirm the selective and delayed neuronal cell death of, especially, the cornu ammonis 1 (CA1) region in the hippocampus [3]. Superoxide and other reactive oxygen species produced by the ischemic insult and zinc release can lead to the production of oxidative stress. Reactive oxygen species (ROS) reverses the protein-mediated sequestration of zinc and increases the intracellular free zinc levels, which increases activation of ROS formation. If it becomes elevated for sustained periods, it can cause neuronal death. Oxidative stress may lead to hippocampal neuronal cell death owing to ischemia and subsequent blood reperfusion
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