Himmelseher S, Pfenninger E, Georgieff M
University Clinic of Anesthesiology, Ulm, Germany.
Anesth Analg. 1996 Sep;83(3):505-12. doi: 10.1097/00000539-199609000-00011.
There is a difference in the relative anesthetic potency of the isomers of ketamine. Neuroprotective differences may therefore also exist. After an 8-min exposure to 500 microM glutamate or axonal transection, cultured rat hippocampal neurons were maintained untreated or in the presence of ketamine-racemate, S(+)-ketamine, or R(-)-ketamine (10(-4) M, 10(-5) M, 10(-6) M). Cell survival was examined by dye inclusion/esterase activity, morphology by phase contrast and immunofluorescence microscopy, and [3H]arachidonic acid (ARA) release by liquid scintillation spectrometry. Seven days after glutamate exposure, survival decreased to 30% in the damaged, untreated group. Extracellular [3H]ARA increased fivefold. Dendritic length and branching decreased to a quarter and axonal extensions to the half. Ketamine-racemate 10(-4) M increased survival to 65%, and induced longer dendrites (P < or = 0.05). S(+)-Ketamine 10(-4) M increased survival to 80%, reduced [3H]ARA threefold, and preserved cytoskeletal arborizations (P < or = 0.05). Axotomy decreased survival to 60% and caused a minor increase in [3H]ARA after 7 days. Survival was 80% after 10(-4) M ketamine-racemate and 90% after 10(-4) M S(+)-ketamine (P < or = 0.05). Only S(+)-ketamine supported axonal reoutgrowth and decreased [3H]ARA (P < or = 0.05). R(-)-Ketamine was ineffective after both types of injury. Ketamine-racemate and S(+)-ketamine attenuated injury after glutamate exposure or axonal transection in hippocampal neurons in vitro. Neuroregenerative effects were uniquely demonstrated by S(+)-ketamine.
氯胺酮异构体的相对麻醉效能存在差异。因此，神经保护作用的差异可能也存在。在培养的大鼠海马神经元暴露于500微摩尔谷氨酸8分钟或轴突横断后，分别在未处理状态下培养，或在消旋氯胺酮、S(+)-氯胺酮或R(-)-氯胺酮（10⁻⁴M、10⁻⁵M、10⁻⁶M）存在的情况下培养。通过染料摄入/酯酶活性检测细胞存活率，通过相差显微镜和免疫荧光显微镜观察形态，通过液体闪烁光谱法检测[³H]花生四烯酸（ARA）释放。谷氨酸暴露7天后，受损未处理组的存活率降至30%。细胞外[³H]ARA增加了五倍。树突长度和分支减少至四分之一，轴突延伸减少至一半。10⁻⁴M消旋氯胺酮使存活率提高到65%，并诱导树突更长（P≤0.05）。10⁻⁴M S(+)-氯胺酮使存活率提高到80%，使[³H]ARA减少三倍，并保留细胞骨架分支（P≤0.05）。轴突切断术后7天，存活率降至60%，并使[³H]ARA略有增加。10⁻⁴M消旋氯胺酮处理后存活率为80%，10⁻⁴M S(+)-氯胺酮处理后存活率为90%（P≤0.05）。只有S(+)-氯胺酮支持轴突再生并减少[³H]ARA（P≤0.05）。两种损伤后，R(-)-氯胺酮均无效。消旋氯胺酮和S(+)-氯胺酮在体外可减轻海马神经元谷氨酸暴露或轴突横断后的损伤。S(+)-氯胺酮具有独特的神经再生作用。
