Limb Remote Ischemic Preconditioning Reduces Repeated Ketamine Exposure-Induced Adverse Effects in the Developing Brain of Rats

AbstractProlonged or repeated exposure to ketamine, a common anesthetic in pediatrics, has been shown to induce neurotoxicity and long-term neurocognitive deficits in the developing brain. Therefore, identification of potential therapeutic targets for preventing or alleviating such neurodegeneration and neuroapoptosis induced by ketamine is urgently needed. Remote ischemic preconditioning of the limb provides neuroprotection in different models of cerebral injury. Thus, the present study aimed to assess whether remote ischemic preconditioning could have a neuroprotective effect against neurotoxicity induced by ketamine. In our study, 96 newborn rats were assigned to one of four groups, including control, remote ischemic preconditioning, ketamine, and remote ischemic preconditioning plus ketamine. Ketamine was administered intraperitoneally in six doses of 20  mg/kg at 2-h intervals. Limb remote ischemic preconditioning comprised four ischemia (5 min)/reperfusion (5 min) cycles in the right hind limb using an elastic rubber band tourniquet. Histopathological characteristics of cerebral damage were assessed by H&E staining and transmission electron microscopy. TUNEL assay, immunohistochemical staining and immunoblot were employed to evaluate neural cell apoptosis. Learning and memory were evaluated using the Morris water maze. The results showed increased cleaved caspase-3 protein levels in the cerebral cortex and the hippocampal CA1 region, severe cell damage and DNA br...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research