Neurodegeneration Overview:
The Biggest Challenge of Current Research
What is neurodegeneration?
Progressive loss (death) of neurons beyond that of the
normal aging process.
However, for most of the “common” neurodegnerative
diseases AGE is the most important risk factor –
spontaneous loss of neurones in the brain and spinal cord
is part of normal ageing process.
It is a problem because neurons cannot be replaced once
they die – techniques involving iPS cells, neuronal
transplantation etc. work in animals and certain
treatments work to some degree in younger patients, but
not in older. Hence, most effective way to treat such
neurodegenerative diseases is likely to be prevention
rather than replacing lost neurones.
Where is it found?
Neurodegenerative diseases – AD, PD, HD (more common in
older patients but early onset versions can occur in
younger individuals, even children)
Other diseases of the nervous system that may cause
neuronal loss:
Cancer – brain tumours often result in neuronal death
Trauma (head/spine injury)- neuronal loss
Viral diseases/Infections e.g. Polio is one of the
most common viral infections that causes neuronal loss
Vascular/Circulatory disorders e.g. Stroke – one of
the main causes of neuronal destruction outside
neurodegeneration
Developmental disorders – inherited conditions often
result in neuronal loss
Vascular and Circulatory Disorders
Stroke: ischemia/infarction
Ischemia = an inadequate blood supply to an organ or part
of the body, especially the heart muscles
Infarction = obstruction of the blood supply to an organ
or region of tissue, typically by a thrombus or embolus,
causing local death of the tissue
Outside of neurodegeneration, the biggest risk factor for
neuronal loss is a stroke (interruption in blood supply
, to the brain). Can be caused by a variety of
mechanisms/risk factors that result in damage to the
brain due to changes in blood circulation…
Atherosclerosis: Narrowing of blood vessels -
multiplication of cells lining blood vessels creating plaque
which restricts blood flow. Many treatments attempt to repair
blocked arteries. Also a risk factor for heart conditions as
well as stroke.
Thrombosis: Damages vessel, infarcts are non-hemorrhagic
Embolism: Heart valve problems, plaques (frequently
hemorrhagic), air trapped in capillaries travelling to
brain tissue
Vasospasm: Rare, but common after subarachnoid
hemorrhage. Subarachnoid membrane covering the brain
spasms, resulting in destruction of neurons.
Hypertensive vasculopathy: Lacunar infarcts. Alterations
in blood vessels in the brain leads to neuronal
destruction.
Transient Ischemic Attacks = a transient episode of
neurologic dysfunction caused by ischemia (loss of blood
flow) – either focal brain, spinal cord, or retinal –
without acute infarction (tissue death).
Two main kinds of stroke:
Ischemic stroke: a clot blocks blood flow to the brain
tissue
-- Pathogenesis: initially, an area of penumbra develops
in the brain, and as the ischemic stroke progresses, more
of this area develops infarction until the area of
penumbra no longer exists. Intervention must be quick to
limit area of penumbra (area possibly preventable in terms of
destruction), so that neurons can potentially recover and
become functional again.
-- Current concept: affected brain region can be divided
into… Core = central area where the effect is. Reversible core
= area of penumbra. Benign oligaemia – astrocytes and
oligodendrocytes are also damaged. A lot of study in terms of
reversing area that is recoverable (reversible core).
Haemorrhagic stroke: bleeding occurs inside or around
brain tissue
Venous Infarction
Venous infarction usually results from venous sinus
thrombosis
Rupturing of blood vessels, blood enters brain and
coagulates, forms huge deposits of hemoglobin in the
The Biggest Challenge of Current Research
What is neurodegeneration?
Progressive loss (death) of neurons beyond that of the
normal aging process.
However, for most of the “common” neurodegnerative
diseases AGE is the most important risk factor –
spontaneous loss of neurones in the brain and spinal cord
is part of normal ageing process.
It is a problem because neurons cannot be replaced once
they die – techniques involving iPS cells, neuronal
transplantation etc. work in animals and certain
treatments work to some degree in younger patients, but
not in older. Hence, most effective way to treat such
neurodegenerative diseases is likely to be prevention
rather than replacing lost neurones.
Where is it found?
Neurodegenerative diseases – AD, PD, HD (more common in
older patients but early onset versions can occur in
younger individuals, even children)
Other diseases of the nervous system that may cause
neuronal loss:
Cancer – brain tumours often result in neuronal death
Trauma (head/spine injury)- neuronal loss
Viral diseases/Infections e.g. Polio is one of the
most common viral infections that causes neuronal loss
Vascular/Circulatory disorders e.g. Stroke – one of
the main causes of neuronal destruction outside
neurodegeneration
Developmental disorders – inherited conditions often
result in neuronal loss
Vascular and Circulatory Disorders
Stroke: ischemia/infarction
Ischemia = an inadequate blood supply to an organ or part
of the body, especially the heart muscles
Infarction = obstruction of the blood supply to an organ
or region of tissue, typically by a thrombus or embolus,
causing local death of the tissue
Outside of neurodegeneration, the biggest risk factor for
neuronal loss is a stroke (interruption in blood supply
, to the brain). Can be caused by a variety of
mechanisms/risk factors that result in damage to the
brain due to changes in blood circulation…
Atherosclerosis: Narrowing of blood vessels -
multiplication of cells lining blood vessels creating plaque
which restricts blood flow. Many treatments attempt to repair
blocked arteries. Also a risk factor for heart conditions as
well as stroke.
Thrombosis: Damages vessel, infarcts are non-hemorrhagic
Embolism: Heart valve problems, plaques (frequently
hemorrhagic), air trapped in capillaries travelling to
brain tissue
Vasospasm: Rare, but common after subarachnoid
hemorrhage. Subarachnoid membrane covering the brain
spasms, resulting in destruction of neurons.
Hypertensive vasculopathy: Lacunar infarcts. Alterations
in blood vessels in the brain leads to neuronal
destruction.
Transient Ischemic Attacks = a transient episode of
neurologic dysfunction caused by ischemia (loss of blood
flow) – either focal brain, spinal cord, or retinal –
without acute infarction (tissue death).
Two main kinds of stroke:
Ischemic stroke: a clot blocks blood flow to the brain
tissue
-- Pathogenesis: initially, an area of penumbra develops
in the brain, and as the ischemic stroke progresses, more
of this area develops infarction until the area of
penumbra no longer exists. Intervention must be quick to
limit area of penumbra (area possibly preventable in terms of
destruction), so that neurons can potentially recover and
become functional again.
-- Current concept: affected brain region can be divided
into… Core = central area where the effect is. Reversible core
= area of penumbra. Benign oligaemia – astrocytes and
oligodendrocytes are also damaged. A lot of study in terms of
reversing area that is recoverable (reversible core).
Haemorrhagic stroke: bleeding occurs inside or around
brain tissue
Venous Infarction
Venous infarction usually results from venous sinus
thrombosis
Rupturing of blood vessels, blood enters brain and
coagulates, forms huge deposits of hemoglobin in the
