CNS病理生理脑功能障碍课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,CNS病理生理脑功能障碍,CNS病理生理脑功能障碍,1,Brain dysfunction,脑功能障碍,Zhihua Gao,Neuroscience Institute,Brain dysfunction脑功能障碍Zhihua,2,Outline,Biology of the brain,Cognitive disorders,认知功能障碍,Conscious disorders,Summary,OutlineBiology of the brain,3,4,Biology of the,b,rain,inside the skull,skull provides protection,but confines the brain,Basics on human adult brain:,Weight: 3 pounds,Size: a medium cauliflower,4Biology of the braininside th,4,Brain nutrition,Blood supply from,twin vertebral arteries,(,椎底动脉,),and carotis interna,l artery,(,颈内动脉,) provides the brain nutrition.,However, nutrients have to pass through the,blood brain barrier (,血脑屏障,),to get into the brain.,Brain nutritionBlood supply fr,5,Blood brain barrier (血脑屏障),BBB consists of:,tight junctions around the capillaries,endothelial cells,a thick basement membrane,astrocyte endfeets,Blood brain barrier (血脑屏障)BBB,6,7,Blood brain barrier (BBB) provides a selective filter for the brain,BBB allows essential metabolites, e.g. oxygen and glucose to diffuse from the blood to the brain, but blocks most molecules (500 Dalton).,Protects the brain from foreign pathogens, e.g. viruses and bacteria,Shields the brain from hormones and neurotransmitters,Maintains brain homeostasis,7Blood brain barrier (BBB) pro,7,8,Brain,m,etabolism,Brain is t,he most active organ in energy metabolism (high demand for blood and oxygen supply).,Glucose is the primary energy source,for brain,; however, the storage of glucose in the brain is very limited.,Take home message:,Brain is highly sensitive to hypoxia and ischemia.,8Brain metabolismBrain is the,8,9,Brain components,100 billions of n,eurons,:,They are executors of brain function.,1000 billions of g,lia,l cells,:,They are supporters and sponsors.,Neurons and glial cells form a complex network to ensure normal brain function.,9Brain components100 billions,9,Cell,communicat,ion in the brain,Functional unit in the brain-synapse,Cell communication in the brai,10,11,Electrical current travels down the axon.,Vesicles move towards,and fuse into,the membrane.,Chemicals are released, diffusing,into the cleft,.,The chemicals bind to the,receptor,on the neighbour cell,opens up channels,and relays,the signal.,Pre-synaptic membrane,Post-synaptic membrane,Synaptic transmission,11Electrical current travels d,11,12,Brain function,Central control of the human body,Maintain cognition,Maintain consciousness,12Brain functionCentral contro,12,Lesion size correlates with symptoms.,Diffusive or localized lesion?,In general,the degree of dysfunction is in proportion to the extent of the damage and the size of the lesion area.,However, there is a r,egion-dependent consequence to brain injuries.,When the injury occurs in the brain stem, a small damage can cause complete loss of consciousness and even death.,Brain lesions: some principles,Lesion size correlates with sy,13,Location determine,s,the symptom,Cerebral cortex damage: cognitive or conscious disorder,Brain stem damage: conscious disorder,Phase determine,s,the symptom,Acute,:,conscious disorder,Chronic,：,cognitive disorder,Brain has very limited capacity for self-repair,-neurons do not regenerate.,Brain lesions: some principles,Location determines the sympto,14,15,Brain responses to lesions,Cellular level,:,Cell,death,of neurons,Degeneration,of,axon,s,/dendrites,Inflammation,triggered by,microglia, astrocytes,Demyelination,of,oligodentrocytes,Systemic level:,Cognitive disorder,(,认知障碍,),Conscious disorder,(,意识障碍,),15Brain responses to lesionsCe,15,16,Outline,Biology of the brain,Cognitive disorder (认知障碍),Conscious disorder (意识障碍),Summary,16OutlineBiology of the brain,16,17,Cognition and cognitive disorder,Cognition,-the process of the brain to sense, handle and acquire information,Involves a series of voluntary psychological and social behaviors, such as study, memory, thinking, judgment and emotion.,Relies on the normal function of the cerebral cortex.,Cognitive disorders-,the disturbance of the process related to cognition,.,usually caused by damages in the cerebral cortex.,17Cognition and cognitive diso,17,Structural Basis of Cognition,Brodmann Mapping (52 areas),Cerebral cortex,Structural Basis of Cognition,18,Structural Basis of Cognition,Structural Basis of Cognition,19,Cognitive disorder,Cognitive disorder,20,Major manifestations of cognitive disorder,Learning and memory def,ec,ts,Aphasia (失语),Hemiplegia (偏瘫),Agraphia (失写),Apraxia (失用),Alexia (失读),Agnosia (失认),Dementia (痴呆),Major manifestations of cognit,21,Frontal lobe,Controls voluntary movement, memory, writing, thinking, creative thoughts, judgment, understanding and social responsibility and personal morals.,When damaged:,Loss of simple movement,Loss of flexibility in thinking,Changes in social behavior,Changes in personality,Inability to express language,Frontal lobe Controls voluntar,22,23,When frontal lobe is damaged:,H,emiplegia,(,偏瘫,),:,paralysis of one side of the body,A,phasia,(,失语,):,partial or total loss of the ability to communicate verbally or using written words,Broca,s aphasia,:,inability to express language (areas 44&45),A,graphia,(,失写,):,A form of aphasia characterized by loss of the ability to write.,D,ementia,(,痴呆,):,loss of mental ability that interferes with normal activities of daily living ( 6 months), without a loss or alteration of consciousness.,23When frontal lobe is damaged,23,24,Processes and discriminates between different sensory inputs,When damaged:,Agraphia (失写):,inability to locate the words for writing,Alexia (失读):,Problems with reading,Agnosia (失认):,Inability to recognize objects,Contralateral sensory deficits,Parietal lobe,24Processes and discriminates,24,25,Is involved in processing sensory (auditory and visual) input, language comprehension and new memories,When damaged,Wernicke,s aphasia (感觉性失语),(area 22， can speak, but meaningless),Spatial or emotional memory,impairment,caused by,hippocampal lesion,(空间与情感记忆障碍),Temporal lobe,25Is involved in processing se,25,Differential diagnosis (DD),Brocas vs Wernickies aphasia,Aphasia is a disturbance of the comprehension and formulation of language caused by dysfunction in specific brain regions.,This class of language disorder ranges from having difficulty remembering words to losing the ability to speak, read, or write. This also affects visual language such as sign language. Wiki definition,Brocas aphrasia:expressive aphrasia (,运动性失语,),loss of the ability to produce language (spoken or written),Wernickies aphrasia: receptive aphrasia (,感觉性失语,),inability to comprehend language or speak with,appropriately meaningful words,Differential diagnosis (DD)Bro,26,27,Visual sensing and processing,Lesions in the primary visual cortex result in defects in visual fields.,Lesions in the visual association cortex result in,loss of objective recognition and of distinguishing the differences,between animals,cat or dog?,Deer or horse?,Occipital lobe,27Visual sensing and processin,27,28,Etiology and Pathogenesis,Chronic brain damage,Chronic systemic diseases,Mental and psychic disorder,Other factors,28Etiology and PathogenesisChr,28,Pathogenesis of cognitive disorder,Pathogenic factors,Changes in neurotransmitters, receptors, neuropeptides and neurotrophic factors,Genetic abnormalities,Chronic,viral infection,Chronic,ischemia,Metabolic abnormalities,Protein aggregation,Abnormal protein modifications,Reduced ATP production, acidosis, elevation of calcium, free radicals and inflammatory factors,Chronic,brain damage,brain dysfunction,Cognitive disorder,Pathogenesis of cognitive diso,29,30,Chronic Brain Damage,Alterations in regulatory molecules,Aberrant protein aggregation,Chronic cerebral ischemic injury,Environmental and metabolic toxins,Cerebral trauma,Brain aging,30Chronic Brain DamageAlterati,30,Alterations in regulatory molecules,Abnormal levels in,Neurotransmitters and receptors,Dopamine,Norepinephrine,Acetylcholine (Ach),Glutamate,Neuropeptides,Neurotrophic factors,Alterations in regulatory mole,31,Dopamine Pathway,Dopamine,Dopamine PathwayDopamine,32,Distribution：Dopamine pathway,Distribution：Dopamine pathway,33,Parkinson Disease,Parkinson Disease,34,Abnormal protein aggregation,Generally seen in a range of neurodegenerative diseases,e.g. Alzheimers disease, Parkinsons disease, Huntingtons disease, Prion disease,Caused by,Gene mutations,Abnormal post-translational modifications,Infection of prion protein in the brain,Abnormal protein aggregationGe,35,Cleaved to generate N-terminal polyQ fragments,Aggregates form in cytoplasm and in nucleus-amyloid-like conformation,Controversy over whether aggregates are toxic or protective,Gain of toxic function and/or loss of protective function,Q,Q,Q,Q,Q,Q,Q,Q,Q,Mutant Huntingtin,in Huntingtons disease,Q,Q,Q,Q,Q,Q,Q,Q,Q,Cleaved to generate N-terminal,36,Mutant,a,-synuclein,in Parkinsons disease,Mutant a-synuclein in Parkins,37,Alzheimers Disease,Alzheimers Disease,38,Alzheimers Disease,Gradual memory loss,Decline in the ability to perform routine tasks,Disorientation,Difficulty in learning,Loss of language skills,Impairment of judgment and planning,Personality changes,Alzheimers Disease Gradual me,39,Senile plaques,Neurofibrillary tangles,Senile plaquesNeurofibrillary,40,CNS病理生理脑功能障碍课件,41,Chronic Cerebral Ischemic Injury,Brain has low energy reserve. Brain is highly sensitive to ischemia and hypoxia.,Neurons die upon complete ischemia for 5 min.,Ischemia causes cognitive disorder likely by the following mechanisms:,Energy exhaustion and acidosis,Intracellular calcium overload,Free radical injury,Excitatory toxicity,Cytokines induced inflammatory reactions,Chronic Cerebral Ischemic Inju,42,Excitatory toxicity,Deficits in energy production, caused by ischemia and hypoxia, inhibits the activity of the Na+-K+-ATPase in plasma membrane, resulting in substantial elevation of extracellular K,+, depolarization of neurons, accompanied by overdosed release of EAA (excitatory amino acids). This leads to the over activation of EAA receptors and neuronal over excitement and death.,EAA: glutamate and aspartate,IAA: GABA and glycine,Excitatory toxicityDeficits in,43,Principles for Treatment of Cognitive Disorders,General neuroprotective treatments,Restore and maintain the normal levels of neurotransmitters and regulatory molecules,Surgery,Principles for Treatment of Co,44,Case studies of cognitive disorder,Phineas Gage,(18231860),Henry Molaison,(1926-2008),Case studies of cognitive diso,45,Phineas Gage- a case of frontal lobe damage,Left frontal lobe damage caused by a mental rod intrusion,He survived after the trauma but his personality had a dramatic change afterwords.,Phineas Gage- a case of fronta,46,47,Learning and memory defects,Henry Molaison (,HM) Patient,An epileptic patient,47Learning and memory defectsH,47,48,HMs lesion includes medial temporal lope structures in addition to hippocampus,(amygdala, entorhinal cortex),Surgery removal of the temporal lobe,48HMs lesion includes medial,48,49,HM,s meomory defects,The surgery had a profound effect on declarative memory,Severe anterograde amnesia,(非常严重的顺行性健忘),M,oderate,retrograde amnesia,(轻微的逆行性健忘),Intact short memory,(,完好的瞬时记忆,),unable to commit new short-term memory into long-term memory,But there was no effect on:,Personality,Attention,Intelligence (normal IQ),Motor skill learning,49HMs meomory defectsThe surg,49,Outline,Biology of the brain,Cognitive disorders,Conscious disorders,Summary,OutlineBiology of the brain,50,51,Consciousness and conscious disorder,Consciousness,refers to individual awareness of self thoughts, memories, feelings, sensations and environment,Two aspects:,State of arousal (by subcortical regions),Responsiveness (controlled by cortex),Conscious disorder,refers to the impairments in maintaining awareness of self and environment and responding to environmental stimuli,51Consciousness and conscious,51,Structural Basis for Consciousness,cerebral cortex,Brain stem reticular formation,thalamus,Structural Basis for Conscious,52,B,rain stem reticular formation,上行激动系统,(ARAS),上行抑制系统,(ARIS),ARAS,的投射纤维终止于大脑皮层广泛区域,主要维持大脑皮层兴奋性，维持觉醒状态和产生意识活动,ARIS,发出的上行纤维行走于,ARAS,大体一致,主要对大脑皮层兴奋性起抑制作用,ARAS,ARIS,Brain stem reticular formation,53,Hypothalamus,由多个核团组成,特异性核团,:,向大脑皮层传递各种特异性感觉信息,非特异性核团,:,接受脑干,网状结构上行纤维并向,大脑皮层广泛部位投射，,参与维持大脑皮层觉醒状态,损害可致长期昏睡。,Hypothalamus由多个核团组成,54,Major manifestations,of conscious disorder,Delirium,Confusion,Stupor,Coma,谵妄,精神错乱,昏睡,昏迷,Major manifestationsDeliriumC,55,Delirium,：意识内容异常为主,的急性精神失常状态,常有睡眠,-,觉醒周期紊乱及错觉、幻觉、兴奋性增高为主的精神运动性改变等。,Confusion,：觉醒与意识内容均出现异常,，一种似睡似醒的状态，常伴有睡眠,-,觉醒周期颠倒。,Stupor,：觉醒状态与意识内容均降至最低水平,，强烈疼痛刺激可出现睁眼、眼球活动等反应，但很快又陷入昏睡状态，病人几乎无随意运动，但,腱反射尚存。,Coma,：觉醒状态、意识内容随意运动持续丧失（,6h,）,或完全丧失的严重意识障碍。可出现,病理反射，,强烈疼痛刺激可引出简单的防御性肢体运动，但不能觉醒。,Delirium：意识内容异常为主的急性精神失常状态,56,Etiology and Pathogenesis,Acute,brain injury,e.,g,. Diffuse encephalic infection, diffuse brain trauma, subarachnoid hemorrhage, etc.,Acute,brain intoxication,Endogenous poisonous lesion,Exogenous poisonous lesion,Intracranial extrusion and destructive lesion,Rapidly expanding or destructive lesions,Etiology and PathogenesisAcute,57,Pathogenesis of conscious disorder,Pathogenic factors,Acute brain lesion,Brain intoxication,Brain tumor,Direct damages to neurons,Axonal injury, cell swelling,Abnormal neurotransmitters,Suppress the brain and brain stem,Abnormalities in the cortex and BSRF function,Conscious disorder,Abnormalities in energy metabolism,Abnormalities in plasma membrane,Pathogenesis of conscious diso,58,59,Principles in Prevention and Therapy,Urgent management,Making a definitive diagnosis ASAP (as soon as possible),Monitoring vital signs and conscious,state,Brain protections,59Principles in Prevention and,59,Outline,Biology of the brain,Cognitive disorders,Conscious disorder,Summary,OutlineBiology of the brain,60,61,Glossary,Cognition, cognitive disorder,Brocas aphasia, Wernickes aphasia, dementia,Conscious disorder, delirium, excitatory toxicity,61GlossaryCognition, cognitive,61,2. Questions,What is the characteristics of brain disorders?,What is the pathogenesis of cognitive disorder?,What is the pathogenesis of consciousn disorder?,2. QuestionsWhat is the charac,62,A case study for you,A case study for you,63,