殷明，医学博士 药理学教授 34206836 13621816556 myin@sjtu

1. 殷明，医学博士 药理学教授 34206836 13621816556 myin@sjtu.edu.cn

2. Drugs that act in the central nervous system1, Introduction to CNS2, General anesthetics

3. Introduction to CNS Anatomy pathways

4. 学习要求（在了解中枢解剖学基础上） 1．掌握神经元、神经胶质细胞、神经突触、血脑屏障的构成与功能。 2．熟悉中枢神经系统重要递质与受体的分布、生理功能及药物作用机制。 3．了解相关神经精神疾病的发病机制与治疗药物。

6. Cortex（皮质，前称：皮层） • evolutionally formed last • receiving and processing information, control of sight, listening, movement, memory, wake, autonomic function…

7. Limbic system（边缘系统） A group of interconnected deep brain structures, common to all mammals, and involved in olfaction, emotion, motivation, behavior, and various autonomic functions. cingulate gyrus:扣带回；pineal：松果 fornix:穹窿；thalamus:丘脑 Pituitary:垂体；amygdala:杏仁 Mammillary body:乳头小体

8. Cerebellum（小脑） responsible for the regulation and coordination of complex voluntary muscular movement as well as the maintenance of posture and balance.

9. The cerebellum has been reported to play a role in psychiatric conditions such as schizophrenia （精神分裂症） autism（自闭症） mood disorders （情感障碍） dementia （痴呆） and attention deficit hyperactivity disorder (ADHD)（多动症）, suggesting …

10. Diencephalon（间脑） • complex of structures • major divisions : thalamus and hypothalamus • functioning • as a relay system between sensory input neurons and other parts of the brain • as an interactive site for the central nervous and endocrine systems • working in tandem with the limbic system

11. thalamus

12. hypothalamus下丘脑：integrative area of autonomic nerve regulation of temperature, water balance, metabolism, blood pressure, circadian rhythm, sex activity, sleeping, etc

14. brain stem 脑干

15. brain stem 脑干 tegmentum(被盖), ascending reticular activating system, NTS (孤束核), area postrema(极后区) regulation of sleeping, wake, eye movement, vomiting, cardiovascular and respiratory reflex

17. Spinal cord脊髓： pathways of senses and movement；autonomic reflex…

18. 神经元 （neuron）

19. 神经元 （neuron） Cellular organization of the brain 1012 neurons 1014 synapses complex networks What is more? Glia cells 90%

21. 神经元突触联系

22. 神经传递过程示意图

23. neuroglial cells (glial cells or glia) D: astrocytes E: oligodendrocyte F:Schwann cell G: microglia

25. Glia (Greek word = glue), not appropriate now. • strocytes, oligodendrocytes, microglial cells, ependymal cells, … • smaller, more in number, conducting no electrical impulses, … • Functions: • to surround neurons and hold them in place, • to supply nutrient and oxygen to neurons, • to insulate one neuron from another, and • to destroy pathogens and remove dead neurons. • More functions remain explored, for example, neurotransmission, … • Allen NJ, Barres BA. (2009). Neuroscience: Glia - more than just brain glue. Nature. 457(7230):675-7 • Those who do not pay attention to glia in neuroscience research are not good neuroscientists.

26. neuropathway 神经通路

27. Mesolimbic(中脑-边缘) pathway: memory and motivating behaviors Mesocortical(中脑-皮质) pathway: thinking and schizophrenia Nigrostriatal(黑质-纹状体) pathway: motor control Tuberoinfundibular(结节-漏斗) pathway: hormones secretion

28. The synapse and synapse potentials

30. pre-synaptic action potential ↓ voltage-sensitive calcium channels ↓ Ca2+ into the terminals ↓ transmitter(s) release ↓ EPSP or IPSP

31. Sites of drug action in synapse transmission 1, presynaptic action potential 2, synthesis 3, storage 7, degradation 4, metabolism 8, receptor 5, release 9, ionic conductance 6, reuptake

32. neurotransmitters at central synapses Ach: acetylcholine NA: norepinephrine DA: dopamine 5-HT: serotonin; 5-hydroxytrptamine GABA: γ-aminobutyric acid glutamate

33. opioid peptides 阿片样肽 histamine 组胺 prostaglandins 前列腺素 tackykinins 速激肽 glycine 甘氨酸 adenosine 腺苷 …

34. Neurotrophic factors （神经营养因子） • a family of proteins that induce the survival, development, and function of neurons. • Nerve growth factor • Brain-derived neurotrophic factor • Neurotrophin-1，3，4 • …

35. Modulators 调质: to modulate the response of a neuron to a neurotransmitter or hormone Transmitter and modulator: action changeable sometimes

36. Blood-brain barrier (BBB) • 1885: Paul Ehrlich: intravenous dyes in experimental organisms caused staining of all organs except the brain • 1913: Edwin Goldmann put forward hypothesis that the cerebral capillaries provide anatomical basis for a physiological barrier between brain and the rest of the body • 1950s: Electron microscopy demonstrated that the outermost layers of endothelial cells in brain capillaries are fused together

39. General anesthetics全身麻醉药学习要求1. 掌握常用全身麻醉药的药理作用及临床应用。2. 熟悉吸入麻醉药的药动学特点及全身麻醉药的作用机制；熟悉常用静脉麻醉药的作用与应用特点。3. 了解复合麻醉的概念。

40. 在比较有效的麻醉剂应用之前， 人们怎么解决手术镇痛问题？

41. 手术镇痛简史 • 针灸 • 公元前五世纪（战国时代）：扁鹊，记载中药麻醉，无从考证 • 公元前二世纪，华陀，麻沸散刮骨疗毒；后人认为主要系曼陀罗主要成分东莨菪碱的中枢抑制作用所致；“蒙汉药” • 19世纪中叶前，国外放血造成休克昏迷行手术；压迫肢体致发麻、冷冻止痛 • 19世纪30年代，国外捆绑或抓住病人进行手术 • 太监的产生：醉酒和/或敲头致昏后去睾丸

42. 1842.3.30, 美国乡村医生Long, 洒有乙醚毛巾捂鼻，切除颈部囊肿成功。未报道。 • 后来，“乙醚麻醉的发明者”

43. 韦尔斯（牙医）：告诉莫顿用氧化亚氮吸入可以麻醉韦尔斯（牙医）：告诉莫顿用氧化亚氮吸入可以麻醉 莫顿请教杰克逊（化学家），后者建议其用乙醚 1846.10.16, Wilian T. Morton（牙医） 首次在哈佛大学麻省总医院行乙醚麻醉演示，切除下颌肿瘤成功 为争发明权： 韦尔斯自杀 莫顿晚年潦倒，死于脑出血 杰克逊罹患精神疾病 Long拒绝加入此官司 莫顿

44. General anaesthesia: a state characterized by unconsciousness, analgesia, amnesia, skeletal muscle relaxation and loss of reflexes. (different from just pain relieving)

50. General anesthetics • airway→alveoli →blood →brain • airway←alveoli ←blood ←brain