Transcript Jelly Fish

Brain dysfunction
Jinghua Jin
Department of Neurobiology
[email protected]
What you have learned about
human brain?
• Anatomy?
– Brain structure?
• Histology?
– Cell types?
• Physiology?
– Brain function?
• Pharmacology?
– Central nervous system drugs ?
Outline
• I: General conception about
human brain
• II: Cognitive disorder
• III: Consciousness disorder
• IV: Summary
1.Structural Characteristics
• It is located inside the skull, protects brain
from injury, confines the brain
• It is composed of neurons and glial cells
• The blood supply is from twin vertebral
arteries and carotis interna
• The brain blood barrier protects brain from
invasion of toxic insults
Human Brain
To understand the dysfunction of
the brain, it’s important to know a
bit about the brain…
The Brain’s Vital Statistics
•Adult weight:
about 3 pounds (~1.5kg)
•Adult size:
a medium cauliflower
•Number of neurons:
100 billion
•Number of synapses:
100 trillion
Inside the Human Brain
Cell Types of the Brain
Neurons
Glia
Structure of Neuron
Neurons
Specialized Regions of Neurons Carry out Different Functions
Hippocampus（海马）
Structure of typical mammalian neurons
Glia
Cellular Functions
• Neuron is in charge of different
functions
• Glia nourishes and protects the
neurons
How are neurons connected?
• Synapses!!
Spine
How does the Synapse carry the signal?
1.
2.
3.
4.
Electrical current travels down the axon
Vesicles with chemicals move toward the membrane
Chemicals are released and diffuse toward the next cell’s plasma
membrane
The chemicals open up the transport proteins and allow the signal
to pass to the next cell
2. Characteristics of Metabolism
• The most active organ in energy
metabolism
• Glucose is almost the only source of brain
energy
• The storage of glucose in the brain is very
limited
3. Characteristics of Brain Disease
• Region-dependent consequences to injuries
– When the cerebral cortex is damaged, the degree of
dysfunction is proportionate to the extent of the damage:
The more extensive the damage, the more severe the
dysfunction is likely to be. However, when the brain
stem is damaged, a relatively small amount of damage
may cause complete loss of consciousness and even
death.
When Specific Areas of the Brain
Are Damaged
3. Characteristics of Brain Disease
• Limited capacity for self repair
Three characteristics of the brain help it compensate
and recover after it has been damaged:
– Redundancy: More than one area can perform the same function.
– Plasticity: Nerve cells in certain areas can change so that they can
perform a different function.
– Adaptation: Areas with somewhat overlapping functions can
sometimes compensate for lost functions.
Brain responses to Injuries
• Cellular responses:
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Neuron death (necrosis, apoptosis)
Degeneration (axon/dendrites retraction, atrophy )
Inflammation (microglia, astrocytes)
Demyelination (oligodentrocytes)
• Functional responses:
– Acute brain damages will cause disturbance in
consciousness: Consciousness disorder
– Chronic lesions usually lead to cognitive dysfunction:
Cognitive disorder
Outline
• I: General conception about
human brain
• II: Cognitive disorder
• III: Consciousness disorder
• IV: Summary
1.Cognition
• The ability of the brain to process and
store information in order to solve
problems.
• It involves a series of voluntary
psychological and social behaviors, such
as study, memory, language, thinking,
emotion etc.
Structural Basis of Cognition
Cerebral cortex
Brodmann Mapping (52 areas)
Function of cerebral cortex
• Frontal cortex: voluntary movements,
complex intellectual activities such as
writing, memory, creativity, judgment,
vision and social responsibility.
– Lesions in this area will result in contralateral
hemiplegia (偏瘫), agraphia （失写症） and
frontal dementia （痴呆）.
– Damage in Broca’s area (44 and 45) result in
motor aphasia (Broca’s aphasia)
Function of cerebral cortex
• Parietal cortex: plays major role in high
level process and integration of sensory
information.
– Lesions in this area produce controlateral
sensory deficits.
– Lesions in the angular gyrus (角回) result in
alexia (失读症) .
– Lesions in the supamarginal gyrus (缘上回)
result in astereognosis (实体感觉缺失).
Function of cerebral cortex
• Temporal cortex: sensory receiving area
for auditory impluses.
– Lesions in area 22 (auditory association
cortex) can lead to Wernicke’s aphasia
– Lesions in temporal hippocampus can
produce spatial or emotional memory
impairment
Function of cerebral cortex
• Occipital cortex: vision
– Lesions in the primary visual cortex result in
visual fields defects.
– Lesions in the visual association cortex result
in a lack of recognition of objects and in
distinguishing the difference of animals (cat vs.
dog).
2. Cognitive Disorder
• The disturbance of the mental process
related to learning and memory, reasoning
and judgment, accompanied by aphasia
(失语), apraxia (失用), agonasia (失认) or
disturbance in executive functioning
Major Manifestations
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Learning and memory disorders
Aphasia
Agonosia
Apraxia
Dementia
Case: Patient H.M.
• Patient HM suffered from epilepsy to his medial temporal lobe (MTLs).
On September 1, 1953, surgeons removed parts of HM's medial
temporal lobe on both sides of his brain. HM lost approximately twothirds of his hippocampal formation, parahippocampal gyrus, and
amygdala. His hippocampus appeared entirely nonfunctional because
the remaining 2 cm of hippocampal tissue appears atrophic and
because the entire entorhinal (which forms the major sensory input to
the hippocampus) was destroyed. Some of his anterolateral temporal
cortex was completely destroyed.
• After the surgery he suffered from severe anterograde amnesia:
although his short-term memory was intact, he could not commit new
events to long-term memory. According to some scientists, HM is
impaired in his ability to form new semantic knowledge but
researchers argue over the extent of this impairment. He also suffered
moderate retrograde amnesia, and could not remember most events
in the 3-4 day period before surgery, and some events up to 11 years
before, meaning that his amnesia was temporally graded. However,
his ability to form long-term procedural memories was still intact; thus
he could, as an example, learn new motor skills, despite not being
able to remember learning them.
Learning and memory deficits:
Patient HM: MRI
HM’s lesion includes
medial temporal lope
structures in addition to
hippocampus
(amygdala, entorhinal
cortex…)
HM’s good news and bad news
• The surgery had a profound effect on declarative
memory
– Severe anterograde amnesia
– Mild retrograde amnesia
– Disability to transfer new short-term memory into long-term
memory
• But there was no effect on:
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–
–
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Personality
Attention
Intelligence
Many forms of memory were spared (short-term memory, motor,
implicit memory, etc).
3. Etiology and Pathogenesis
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Chronic brain damage
Chronic systemic diseases
Mental and psychic disorder
Other factors
Chronic Brain Damage
• Imbalance of regulating molecules in the
brain
• Protein aggregation in the brain
• Chronic cerebral ischemic injury
• Environmental and metabolic toxins
• Cerebral trauma
• Brain aging
(1) Imbalance of Regulating Molecules
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Dopamine
Norepinephrine
Acetylcholine (Ach)
Glutamate
Aberrant neuropeptide
Lack of neurotrophic factors
Dopamine
Dopamine
Pathway
Dopamine Synthesis and Storage
Tyrosine  L-DOPA  DA
Distribution：Dopamine pathway
Parkinson Disease
(2) Protein Aggregation in the Brain
• Gene mutations
• Abnormal post-translational modification
• Infection of slow virus in the brain
Mutant Huntingtin in Huntington’s disease
Q Q
QQ Q Q Q
Q Q
•Cleaved to generate N-terminal polyQ fragments
•Aggregates form in cytoplasm and in nucleus-amyloidlike conformation
•Controversy over whether aggregates are toxic or
protective
•Gain of toxic function and/or loss of protective function
Mutant a-synuclein in Parkinson’s disease
Alzheimer Disease
Alzheimer’s 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
Senile plaques
Neurofibrillary tangles
(3) Chronic Cerebral Ischemic Injury
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Energy exhaustion and acidosis
Intracellular calcium overload
Free radical injury
Excitatory toxicity
Inflammatory reaction by cytokine
Glutamate
Excitatory toxicity
• A general pathologic process beginning with the energy
and metabolic dysfunction caused by cerebral ischemia
and anoxia, which then result in inhibition of Na+-K+ATPase in plasma membrane, elevation of extracellular
K+ and depolarization of neurons. These changes then
cause overdosed release of EAA (excitatory amino acids)
into the synaptic cleft and overacitvation of EAA receptor,
ultimately over excitement and death of neurons.
Pathogenesis of Cognitive Disorder
4. Principles for Treatment of
Cognitive Disorders
• General neuroprotective treatments
• Maintenance of normal
neurotransmitter level
• Surgery
Outline
• I: General conception about
human brain
• II: Cognitive disorder
• III: Consciousness disorder
• IV: Summary
1. Consciousness
• The sense of awareness of self and the
environment.
• It consists of two aspects:
– State of arousal and content of consciousness.
2. Consciousness Disorder
• Parenchymal mental disorders in which
there is impairment of the ability to
maintain awareness of self and
environment and to respond to
environmental stimuli.
Structural Basis for Consciousness
Structural Basis for Consciousness
disorders
• Dysfunction of brain stem reticular
formation
• Dysfunction of thalamus
• Dysfunction of cerebral cortex
Major Manifestations
Coma
Drowsiness
Confusion
Delirium
3. Etiology and Pathogenesis
• Acute brain injury
– eg. Diffuse encephalic infection, diffuse brain
trauma, subarachnoid hemorrhage, etc.
• Acute brain intoxication
• Intracranial extrusion and destructive
lesion
Acute Brain Intoxication
• Endogeneous toxins injury
– Alteration in neurotransmitter
– Aberrant energy metabolism
– Nerve cell membrane injury
• Exogenous toxins injury
Etiology and Pathogenesis of
Consciousness Disturbance
4. Principles of Prevention and Therapy
• Urgent management
• Making a definite diagnosis as soon as
possible
• Monitoring vital signs and consciousness
state
• Brain protections
Outline
• I: General conception about
human brain
• II: Cognitive disorder
• III: Consciousness disorder
• IV: Summary
1. Glossary
• cognition, cognitive disorder, Broca’s
aphasia, Wernicke’s aphasia, hemiplegia,
agraphia, apraxia, agonasia, alexia,
astereognosis, dementia, consciousness
disorder, delirium, confusion, drowsiness,
coma, excitatory toxicity.
2. Questions
• 1. What is the characteristics of brain
disease?
• 2. What is the pathogenesis of cognitive
disorder?
• 3. What is the pathogenesis of
consciousness disorder?