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Dexmedetomidine provides neuroprotection: impact on ketamine‐induced neuroapoptosis in the developing rat brain
Author(s) -
DUAN X.,
LI Y.,
ZHOU C.,
HUANG L.,
DONG Z.
Publication year - 2014
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12356
Subject(s) - dexmedetomidine , dentate gyrus , medicine , ketamine , saline , tunel assay , neurotoxicity , neuroprotection , anesthesia , morris water navigation task , intraperitoneal injection , subcutaneous injection , nmda receptor , hippocampus , apoptosis , endocrinology , toxicity , immunohistochemistry , receptor , biology , biochemistry , sedation
Background Ketamine and dexmedetomidine are increasingly used in combination in pediatric patients. This study examined the hypothesis that dexmedetomidine attenuated ketamine‐induced neurotoxicity. Methods Neonatal rats were randomly divided into four groups ( n = 10, male 5, female 5). Group S + S received an equal volume of normal saline intraperitoneally and subcutaneously at an interval of 5 min. Group K + S received an intraperitoneal injection of 75 mg/kg ketamine followed by subcutaneous injection of normal saline 5 min later. Group S + D were given subcutaneously 25 μg/kg dexmedetomidine 5 min after injection of normal saline. Group K + D received a subcutaneous injection of 25 μg/kg dexmedetomidine 5 min after ketamine injection. The above drugs were given once daily for 3 days. Neuronal apoptosis in the CA 1 region and the dentate gyrus of rats was examined by transferase dUTP nick end labeling ( TUNEL ) assays. Learning and memory abilities of 2‐month old rats were examined by Morris water maze test. The results were analyzed by analysis of variance. Results The percentage of TUNEL ‐positive cells in group K + S ( CA 1, 49.0 ± 9.46 and dentate gyrus, 49.4 ± 5.41) was markedly higher than that in group K + D (CA1, 37.2 ± 5.54 and dentate gyrus, 35.2 ± 5.06) (F = 5.49, P < 0.05 and F = 13.51, P < 0.001, respectively). Group K + S took significantly longer time and swimming distance to find the hidden platform on the fourth and fifth training days than group K + D ( P < 0.05). Moreover, group K + D spent considerably more time in the target quadrant than group K + S ( P < 0.05). Dexmedetomidine alone caused a small but statistically insignificant increase in neuronal apoptosis of the CA 1 region and the dentate gyrus of neonatal rats compared with normal saline. Conclusion In conclusion, ketamine caused neuroapoptosis and impaired brain functions in the developing rat brain which can be effectively attenuated by dexmedetomidine. Dexmedetomidine alone was not neurotoxic to the developing brain.