Noxious stimulation attenuates ketamine-induced neuroapoptosis in the developing rat brain

Jia Ren Liu, Qian Liu, Jing Li, Chongwha Baek, Xiao Hui Han, Umeshkumar Athiraman, Sulpicio G. Soriano

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Background: Ketamine induces neuroapoptosis in neonatal rodents. However, these experimental paradigms were performed without concurrent noxious stimulation, a condition that does not reflect the interaction of anesthesia and surgical stimulation. Noxious stimulation with and without concurrent analgesic drugs has been shown to have divergent patterns of neuronal activation and cell death. We hypothesized that concurrent noxious stimulation would attenuate ketamine-induced caspase-3 activation. Methods: Postnatal day 7 Sprague-Dawley rat pups were randomized to a 6-h exposure to ketamine with and without peripheral noxious stimulation by intraplantar injection of complete Freund's adjuvant. A cohort of naïve rat pups with and without complete Freund's adjuvant injections served as control subjects. Neuroapoptosis was measured by cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2′-deoxyuridine 5′-triphosphate nick end labeling staining. In order to determine if concurrent noxious simulation altered the expression of cell survival and cell cycle proteins, levels of protein kinase B and glycogen synthase kinase-3β and cyclin D1 were measured. Results: Ketamine induced a significant increase in cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2′-deoxyuridine 5′- triphosphate nick end labeling staining with increases in cyclin D1 levels. Concurrent noxious stimulation with ketamine attenuated caspase-3 activation and maintained cyclin D1 levels. Phosphorylation of protein kinase B and glycogen synthase kinase-3β was not definitively altered under these conditions. Conclusion: The administration of ketamine with concurrent noxious stimulation results in the attenuation of the neuroapoptotic response. These findings suggest that concurrent surgery and procedural pain attenuates ketamine-induced neuroapoptosis.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalAnesthesiology
Volume117
Issue number1
DOIs
StatePublished - Jul 2012

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