Tachibana Kaori, Hashimoto Toshikazu, Kato Rui, Uchida Yosuke, Ito Ryoko, Takita Koichi, Morimoto Yuji
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Paediatr Anaesth. 2012 Jul;22(7):713-9. doi: 10.1111/j.1460-9592.2012.03810.x. Epub 2012 Feb 6.
The use of dexmedetomidine (DEX), a selective alpha-2 agonist, in pediatric practice is expanding as a result of its desirable properties. To clarify the long-term neurological consequences of neonatal administration of DEX, we investigated the long-term effects of neonatal administration of DEX on hippocampal synaptic activity.
The rat pups received a bolus intraperitoneal injection of either 5 or 10 μg·kg(-1) DEX, or an equivalent volume of vehicle on postnatal day 7 (P7). Nine weeks after administration, evoked potentials (population spike, PS) and long-term potentiation (LTP) in the hippocampal CA1 region of rats were studied in vivo.
Dexmedetomidine had a considerable sedative effect at these doses with little respiratory depression on P7. Nine weeks after administration of DEX, the amplitude of PS in the two treated groups was similar to that in the control group. DEX-treated rats showed no impairment in the induction of LTP. Furthermore, the response in PS to the paired stimuli was not impaired by neonatal administration of DEX.
These findings demonstrate that a single administration of DEX to rats on P7 preserves hippocampal synaptic plasticity as well as synaptic transmission later in life. In view of the some evidence that have demonstrated the permanent detrimental impact of commonly used anesthetics on neurological outcomes after neonatal exposure, our findings may suggest the relative safety of DEX administered as a sedative agent to neonatal animals with regard to the development of hippocampal synaptic functions.
由于具有理想的特性，选择性α-2激动剂右美托咪定（DEX）在儿科临床中的应用正在不断扩大。为阐明新生期给予DEX的长期神经学后果，我们研究了新生期给予DEX对海马突触活性的长期影响。
在出生后第7天（P7），给幼鼠腹腔注射一次5或10μg·kg-1的DEX，或等量的溶剂。给药9周后，在体研究大鼠海马CA1区的诱发电位（群体峰电位，PS）和长时程增强（LTP）。
在这些剂量下，右美托咪定在P7时具有显著的镇静作用，几乎没有呼吸抑制。给予DEX 9周后，两个治疗组的PS幅度与对照组相似。DEX治疗的大鼠在LTP诱导方面没有受损。此外，新生期给予DEX对PS对配对刺激的反应没有损害。
这些发现表明，在P7给大鼠单次给予DEX可在其生命后期保留海马突触可塑性以及突触传递。鉴于一些证据表明常用麻醉剂对新生期暴露后的神经学结局有永久性有害影响，我们的发现可能提示，就海马突触功能发育而言，DEX作为镇静剂给予新生动物具有相对安全性。
