神经生物学课件 脑缺血2013研究生
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Ischemia 缺血: shortage of the blood supply (oxygen, glucose, etc)
Hypoxia 缺氧: shortage of oxygen
Anoxia 缺氧: an extreme form of hypoxia, absence of oxygen
OUTLINE
1, Fra Baidu bibliotekhat is ischemic brain injury? 2, Why does ischemia cause brain injury?
Experimental models Prominent Mechanisms leading to brain injury 3, How does the brain repair/protect itself after stroke? 4, Translational strategies
back; see segh- in Indo-European roots + haima, blood ) http://www.thefreedictionary.com/ischemia
May also be spelled as: ischaemia or ischæ mia
Related Terms
全脑缺血模型中，海马神经元最易受影响
Hypoxia-ischemia model
ligation of the right (or left) common carotid artery of 7day-old pups, followed by 90 minute of hypoxia (8% 02 and 92% N2) at 37°C.
Right: Rose bengal dyephotosensitized dMCA thrombus
Images from http://neurology.med.miami.edu/x301.xml
光化学诱导模型可用于研究溶栓药物的作用
Images from http://sitemaker.umich.edu/lawrence.lab/files/page_4_01.html
Macrophages
Cyst formation
神经细胞受损
缺血1h再灌 24h，同侧和对侧皮层、纹状 体神经元变化（CV染色）
cortex
contralateral
ipsilateral
striatum
Severely damaged tissue
Low perfusion tissue
Ischemic core appears within minutes to hours.
大脑中动脉栓塞
Longa, E. Z., P. R. Weinstein, S. Carlson, R. Cummins (1989). "Reversible middle cerebral artery occlusion without craniectomy in rats". Stroke 20 (1): 84– 91. PMID 2643202
hypertensive rats)
Global brain ischemia：
➢ Four-vessel occlusion 四血管结扎 ➢ Common carotid artery occlusion in gerbils ➢ Two-vessel occlusion plus hypotention 两血管结扎并低
血压 ➢ Cardiac arrest cerebral ischemia (CACI) 心脏骤停 ➢ Hypoxic ischemia 低氧缺血 ➢ Intracranial hypertension and common carotid artery occlusion
Intraluminal suture MCAO
rose bengal 玫瑰红B 四碘四氯荧光素二钠
Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. (1985). Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 17(5):497-504
Brain ischemia 脑缺血: insufficient blood flow to the brain (eg: ischemic
stroke)
Ischemic cascade 缺血级联反应: a series of biochemical reactions that take place after seconds to minutes of ischemia.
Photothrombosis stroke model
Photosensitive dye: rose bengal
Specific lighting: 卤素灯或氙灯
Photochemical reaction products:
reactive oxygen species
Damage: Vascular endothelial cell injury Thrombosis formation
Focal brain ischemia (transient/ permanent)：
➢ Middle cerebral artery occlusion (MCAO) ➢ Photothrombosis 光化学诱导 ➢ Spontaneous brain infarction (in spontaneously
缺血性脑损伤及脑保护
Ischemic Brain Injury and Protection
2013-11
OUTLINE
1, What is ischemic brain injury? 2, Why does ischemia cause brain injury?
Experimental models Prominent Mechanisms leading to brain injury 3, How does the brain repair/protect itself after stroke? 4, Translational strategies
ISCHEMIA is:
A decrease in the blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of the blood vessels.
(New Latin ischaemia, from Greek iskhaimos, a stopping of the blood : iskhein, to keep
After hours to days, ischemic core territory expands.
脑缺血造成脑梗死
缺血核心区 ischemic core 缺血半影区 penumbra
Ischemic core:
➢ irreversibly damaged tissues distal to an occluded blood vessels ➢ < 20% of baseline blood flow levels ➢ depleted ATP stores ➢ irreversible failure of energy metabolism
Rat, mice, and gerbil are the commonly used model animals.
Monkey, cat, and rabbit are also used to establish stroke models.
外周血液经两对动脉进入脑内：颈动脉和椎动脉 阻断血流（颅内、颅外）：脑缺血
Salvageable tissue is the target for therapy.
Ischemic penumbra:
➢ significantly depressed tissue perfusion ➢ barely sufficient to support basal ATP levels as well as normal ionic gradients in the presence of electrical silence and suppressed protein synthesis ➢ “at risk” region: functionally impaired, potentially salvageable
dysfunction occurs 10 seconds: no oxygen supply
within seconds to minutes of vessel occlusion
30 seconds: changes in brain metabolism 1 minute: no neuronal functional activities 6-8 minutes → neuronal death, Infarction
Stroke types and incidence
中风中绝大多数是缺血性中风
Blockage of a blood vessel (in the brain or neck)
脑血栓形成
脑栓塞
Cerebral ischemia
Ischemic Brain Injury
Neurological
Few seconds: little or no damage
缺血半影区的神经元病理变化：
ischemia
Damage Mechanisms
Protective Mechanisms
1，启动细胞死亡机制
2，激活脑内自身保护机制
Cell Fate
Live? Dead?
OUTLINE
1, What is ischemic brain injury? 2, Why does ischemia cause brain injury?
Ischemic injury and cell death continues in stages for minutes, hours, and even days of vessel occlusion
血栓使大脑中 动脉栓塞，供 血区血供不足
脑水肿
大脑中动脉缺血
Oedema
Red Neurons
Experimental models Prominent Mechanisms leading to brain injury 3, How does the brain repair/protect itself after stroke? 4, Translational strategies
Left: Cortical “spot” lesion, carbon black view at 4 h
Right: Occluded arteriole in pia, perfused at 2 min; SEM x4160
Left: 562 nm dye laser beam positioned on dMCA
MCAO-induced stroke model in rhesus monkey
大鼠行为学视频
MCAO induces brain edema (bottom left) and infarction (right). Top left shows MCAO-affected region in human brain.
Hypoxia chamber
Images from Journal of Cerebral Blood Flow & Metabolism (2004) 24, 259–270
In Vitro culture
Cell culture Organotypic brain slice culture
Hypoxia 缺氧: shortage of oxygen
Anoxia 缺氧: an extreme form of hypoxia, absence of oxygen
OUTLINE
1, Fra Baidu bibliotekhat is ischemic brain injury? 2, Why does ischemia cause brain injury?
Experimental models Prominent Mechanisms leading to brain injury 3, How does the brain repair/protect itself after stroke? 4, Translational strategies
back; see segh- in Indo-European roots + haima, blood ) http://www.thefreedictionary.com/ischemia
May also be spelled as: ischaemia or ischæ mia
Related Terms
全脑缺血模型中，海马神经元最易受影响
Hypoxia-ischemia model
ligation of the right (or left) common carotid artery of 7day-old pups, followed by 90 minute of hypoxia (8% 02 and 92% N2) at 37°C.
Right: Rose bengal dyephotosensitized dMCA thrombus
Images from http://neurology.med.miami.edu/x301.xml
光化学诱导模型可用于研究溶栓药物的作用
Images from http://sitemaker.umich.edu/lawrence.lab/files/page_4_01.html
Macrophages
Cyst formation
神经细胞受损
缺血1h再灌 24h，同侧和对侧皮层、纹状 体神经元变化（CV染色）
cortex
contralateral
ipsilateral
striatum
Severely damaged tissue
Low perfusion tissue
Ischemic core appears within minutes to hours.
大脑中动脉栓塞
Longa, E. Z., P. R. Weinstein, S. Carlson, R. Cummins (1989). "Reversible middle cerebral artery occlusion without craniectomy in rats". Stroke 20 (1): 84– 91. PMID 2643202
hypertensive rats)
Global brain ischemia：
➢ Four-vessel occlusion 四血管结扎 ➢ Common carotid artery occlusion in gerbils ➢ Two-vessel occlusion plus hypotention 两血管结扎并低
血压 ➢ Cardiac arrest cerebral ischemia (CACI) 心脏骤停 ➢ Hypoxic ischemia 低氧缺血 ➢ Intracranial hypertension and common carotid artery occlusion
Intraluminal suture MCAO
rose bengal 玫瑰红B 四碘四氯荧光素二钠
Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. (1985). Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 17(5):497-504
Brain ischemia 脑缺血: insufficient blood flow to the brain (eg: ischemic
stroke)
Ischemic cascade 缺血级联反应: a series of biochemical reactions that take place after seconds to minutes of ischemia.
Photothrombosis stroke model
Photosensitive dye: rose bengal
Specific lighting: 卤素灯或氙灯
Photochemical reaction products:
reactive oxygen species
Damage: Vascular endothelial cell injury Thrombosis formation
Focal brain ischemia (transient/ permanent)：
➢ Middle cerebral artery occlusion (MCAO) ➢ Photothrombosis 光化学诱导 ➢ Spontaneous brain infarction (in spontaneously
缺血性脑损伤及脑保护
Ischemic Brain Injury and Protection
2013-11
OUTLINE
1, What is ischemic brain injury? 2, Why does ischemia cause brain injury?
Experimental models Prominent Mechanisms leading to brain injury 3, How does the brain repair/protect itself after stroke? 4, Translational strategies
ISCHEMIA is:
A decrease in the blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of the blood vessels.
(New Latin ischaemia, from Greek iskhaimos, a stopping of the blood : iskhein, to keep
After hours to days, ischemic core territory expands.
脑缺血造成脑梗死
缺血核心区 ischemic core 缺血半影区 penumbra
Ischemic core:
➢ irreversibly damaged tissues distal to an occluded blood vessels ➢ < 20% of baseline blood flow levels ➢ depleted ATP stores ➢ irreversible failure of energy metabolism
Rat, mice, and gerbil are the commonly used model animals.
Monkey, cat, and rabbit are also used to establish stroke models.
外周血液经两对动脉进入脑内：颈动脉和椎动脉 阻断血流（颅内、颅外）：脑缺血
Salvageable tissue is the target for therapy.
Ischemic penumbra:
➢ significantly depressed tissue perfusion ➢ barely sufficient to support basal ATP levels as well as normal ionic gradients in the presence of electrical silence and suppressed protein synthesis ➢ “at risk” region: functionally impaired, potentially salvageable
dysfunction occurs 10 seconds: no oxygen supply
within seconds to minutes of vessel occlusion
30 seconds: changes in brain metabolism 1 minute: no neuronal functional activities 6-8 minutes → neuronal death, Infarction
Stroke types and incidence
中风中绝大多数是缺血性中风
Blockage of a blood vessel (in the brain or neck)
脑血栓形成
脑栓塞
Cerebral ischemia
Ischemic Brain Injury
Neurological
Few seconds: little or no damage
缺血半影区的神经元病理变化：
ischemia
Damage Mechanisms
Protective Mechanisms
1，启动细胞死亡机制
2，激活脑内自身保护机制
Cell Fate
Live? Dead?
OUTLINE
1, What is ischemic brain injury? 2, Why does ischemia cause brain injury?
Ischemic injury and cell death continues in stages for minutes, hours, and even days of vessel occlusion
血栓使大脑中 动脉栓塞，供 血区血供不足
脑水肿
大脑中动脉缺血
Oedema
Red Neurons
Experimental models Prominent Mechanisms leading to brain injury 3, How does the brain repair/protect itself after stroke? 4, Translational strategies
Left: Cortical “spot” lesion, carbon black view at 4 h
Right: Occluded arteriole in pia, perfused at 2 min; SEM x4160
Left: 562 nm dye laser beam positioned on dMCA
MCAO-induced stroke model in rhesus monkey
大鼠行为学视频
MCAO induces brain edema (bottom left) and infarction (right). Top left shows MCAO-affected region in human brain.
Hypoxia chamber
Images from Journal of Cerebral Blood Flow & Metabolism (2004) 24, 259–270
In Vitro culture
Cell culture Organotypic brain slice culture