Abstract
Background Stroke is a major worldwide problem that is leading to a high mortality rate in humans. Ischemia, as the most common type of stroke, is characterized by tissue damage that can occur due to insufficient blood flow to the brain even for a brief duration, leading to the release of inflammatory factors, cytokines, and free radicals. In this study, we investigated the effective dose and injection time of FK506 as an immunophilin ligand for providing a suitable effect on cells of CA2, CA3, and dentate gyrus of the hippocampus. Methods In this in vivo study, a total of 48 male Wistar rats were divided into nine groups. The ischemia model was induced by the ligation of bilateral common carotid arteries. The doses of FK506 (3, 6, and 10 mg/kg) were administered intravenously (IV) at the beginning of reperfusion, followed by repeated injections (10 mg/kg) at 6, 24, 48, and 72 hours after ischemia, respectively. Brains were removed and prepared for Nissl staining and the TdT-mediated dUTP Nick End Labeling method. Results Data showed that global ischemia did not decrease the number of viable pyramidal cells in CA2 and CA3 regions, but significant differences were observed in the number of viable granular cells and apoptotic bodies in the dentate gyrus between the control and ischemia groups. Repeated doses of 6 mg/kg of FK506 at an interval of 48 hours were deemed to be the suitable dose and best time of injection. Conclusions It seems that FK506 can ameliorate the extent of apoptosis and may be a good candidate for the treatment of ischemia-induced brain damage.
Highlights
Hippocampus is a small part of the human brain which plays roles in memory forming, organizing, and storing
Reperfusion injuries refer to the tissue damage caused by the restoration of blood to a tissue after a period of ischemia; a special condition is caused by the absence of oxygen and nutrients during the period of ischemia, in which inflammation and oxidative damage result from the induction of oxidative stress once the blood supply is restored [5,6,7]
Results showed that clamping the common carotid arteries for 20 min could not reduce the number of viable pyramidal cells in the hippocampal CA3 and CA2 regions, so there was no statistically significant difference between the control and ischemia groups (P=0.659)
Summary
Stroke is a major worldwide problem that is leading to a high mortality rate in humans. As the most common type of stroke, is characterized by tissue damage that can occur due to insufficient blood flow to the brain even for a brief duration, leading to the release of inflammatory factors, cytokines, and free radicals. We investigated the effective dose and injection time of FK506 as an immunophilin ligand for providing a suitable effect on cells of CA2, CA3, and dentate gyrus of the hippocampus. The doses of FK506 (3, 6, and 10 mg/kg) were administered intravenously (IV) at the beginning of reperfusion, followed by repeated injections (10 mg/kg) at 6, 24, 48, and 72 hours after ischemia, respectively. It seems that FK506 can ameliorate the extent of apoptosis and may be a good candidate for the treatment of ischemia-induced brain damage
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