Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain.

Objective: Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity.
Materials and Methods: To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test.
Results: The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p < 0.05) but not in the CA1 region (p > 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age.
Conclusions: Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection.