title: [Comparison of dexmedetomidine and midazolam on neurotoxicity in neonatal mice].
abstract: Dexmedetomidine and midazolam have been widely used in clinical anesthesia and intensive care unit sedation. These two drugs differ in sedative mechanism. We hypothesized that the neurotoxicity of repeated exposure to dexmedetomidine or midazolam for neonatal mice might be different. Twenty four mice of postnatal day 8 were randomly divided into control (n=8), dexmedetomidine (n=8) and midazolam group (n=8) respectively. In the three groups, saline(10mL/kg), dexmedetomidine(10microg/kg) or midazolam(40mg/kg) was injected intraperitoneally once a day, in the next five days, respectively. Then the brains of the mice in the three qroups were removed and cryosectioned. Apoptotic neural cell in hippocampus region was detected with terminal deoxynucleotydyl transferase -mediated dUTP nick end labeling(TUNEL). Bcl2 and Bax protein expression level in the hippocampus were determined by immunofluorescent staining. In the present study, the number of TUNEL-positive cells from midazolam group ((20 +/-3) /mm2) was larger than that from dexmedetomidine group ((15+/-2) /mm2, P<0. 05) and control group((13+/-3) /mm2, P<0. 05); Bcl-2 protein quantity in hippocampus from control group((790+/-103)/mm2)was significantly lower than that in midazolam group((1187+/- 162)/mm2, P<0.05)and dexmedetomidine group((890+/-125)/mm2, P<0. 05). Bax protein level in control group((942+/-104)/mm2) was also significantly lower than that in midazolam group((1839+/-160)/mm2, P<0. 05)and dexmedetomidine group((1143+/-125)/mm2, P<0. 05); Bax/Bcl-2 ratio in midazolam group(0. 64+/-0. 13) was significantly lower than that in dexmedetomidine group(0. 78 +/-0. 14, P<0. 05) and control group(0. 84+/-0. 15, P<0. 05). Our results suggest that dexmedetomidine has lower neurotoxicity than midazolam for neonatal mice.
authors.affiliation: Department of Anesthesiology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Luo
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.forename: Dongmei
authors.initials: D
authors.lastname: Han
authors.forename: Huafeng
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D020927:Dexmedetomidine / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008874:Midazolam / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D020927:Dexmedetomidine; D008874:Midazolam