老龄患者对全麻药敏感性增加,易诱发爆发抑制(BS)和等电位(IE)脑电状态,导致预后不良。我们研究发现老龄鼠七氟醚诱发BS和IE最低肺泡有效浓度(MACbs和MACie)降低,脑室内注射OrexinA难以逆转BS和IE状态,可能与老龄鼠“睡眠觉醒”调控通路Orexin能和蓝斑NE能神经失能有关。我们研究发现突触前膜蛋白Synapsin1磷酸化异常在老龄普遍存在，导致突触囊泡神经递质释放障碍,可能参与Orexin能和蓝斑NE能神经环路失能。本研究重点观察老龄鼠Orexin能和蓝斑NE能神经突触蛋白Synapsin家族改变,和对吸入性全麻药MACbs和MACie的影响,通过动物行为学、神经生物学、神经药理学、光基因遗传学及膜片钳等方法,明确老龄性Orexin能和蓝斑NE能神经环路突触失能,增加全麻药物诱发BS和IE风险的解剖学基础、神经环路特征及分子机制,探讨预测全麻药效和预防不良预后方法。

Sensitivity to general anesthetics increased in geriatric patients, resulting in more risks for inducing burst suppression (BS) and isoelectric electroencephalogram (IE) during anesthesia,which are associated with unfavourable prognosis. Our previous study has demonstrated that minimum alveolar concentration of sevoflurane for inducing BS (MACbs) and IE (MACie) decreased in aged rats and can not be reversed by intraventricle injection of OrexinA, which implied an impaired function of “sleep-arouse”circuit involving orexin and locus coeruleus norepinephrine neuron. Our previous study revealed that decreased phosphorylation of presynaptic protein Synapsin1 is common in aging associated neural degeneration diseases, which will result in disorder of synaptic vesicle release and may involve in dysfunction of orexin and locus coeruleus norepinephrine neural circuit in aged population. Present project focuses on aging asociated changes of synapsin family in orexin and locus coeruleus norepinephrine neural circuit, and it relationship with the increased sensitivity to volatile anesthetics. Take the advantage of advanced techniques in animal behavioristics, neurobiology, neuropharmacology, optogenetic methods, and patch clamp techniques, we aim to reval the anatomic structure,neural circuit characteristics,and molecule mechanism of synaptic dysfunction in orexin and locus coeruleus norepinephrine neural circuit, and its relationship with the development of higher sensitivity to volatile anesthetics and increased risks for inducing BS and IE in aged population. Possible strategies for prediction of sensitivity to volatile anesthetics and prevention of unfavourable prognosis are also studied.