Ischemia Flashcards
How does the brain use energy?
75% for signaling
25% for essential cellular activity.
Are metabolic rates higher in gray matter or in white matter?
gray matter
How do energy-rich substrates enter brain from the blood?
Via the blood-brain barrier.
There are transporters for glucose and monocarboxylic acids at the barrier.
What does the brain use as fuel?
Glucose, glycogen, lactate, ketone bodies.
Carbohydrate oxidation is the main source of energy in the brain.
Why do excitatory and inhibitory neurons consume equivalent energy?
Because they do equivalent work.
Which cerebral vessel has a lower oxygen concentration?
cerebral venous blood.
What molecule is made in the astrocytes?
glycogen
Glycogen is converted into what molecule that is eventually diffused into neurons?
lactate
What metabolic pathways are used in the brain?
glycolysis
glycogenolysis
pentose phosphate shunt
malate aspartate shuttle
TCA cycle
What are some experimental models used for the analysis of ischemias?
Primary neuronal cultures or co-cultures
cell lines
brain
surgical methods performed in live animals
in vivo imaging techniques
What is a negative of brain imaging?
Changes in small structures are not detectable.
What does brain imaging do?
Shows metabolic rates of imaging for the whole brain.
What molecule is usd in PET imaging?
analogs of glucose. It relies on a metabolite, which enables assays of the hexokinase reaction in all regions of the brain in conscious individuals.
What is magnetic resonance spectroscopy?
An imaging method that uses glucose.
It allows assessment of glucose metabolites as they are formed in different pathways.
What is the purpose of magnetic responance spectroscopy?
To obtain an NMR that determines the metabolism of precursors via specific neuronal and glial pathways.
True or false: the human brain is inneficient in terms of energy usage.
True
What is Magnetic Resonance Spectroscopy (MRS)?
Allows for the assessment of glucose metabolites as they are formed in different pathways.
It is used to determine metabolism of precursors via specific neuronal and glial pathways.
What is focal cerebral ischemia?
Focal disruption of blood flow to a part of the brain due to occlusion of an artery by an embolus.
What is global cerebral ischemia?
Transient impairment of blood flow to the whole brain (e.g. during cardiac arrest).
What type of ischemia accounts for a majority of strokes?
focal ischemia
How does a focal ischemia occur?
When an artery supplying a brain region is occluded by an embolus, thrombus or platelet plug.
What is an ischemia core/umbra?
The core of neural tissue that is affected by the stroke.
What is the penumbra?
A rim/area surrounding the umbra.
It is an area of reduced cerebral flow, impaired protein synthesis and preserved energy metabolism.
In an acute focal ischemia, what is the focus on?
saving the penumbra
You enounter a patient who is experiencing a cardiac arrest. Prior to resusciation, they also experience an ischemia. What type of ischemia are they most likely suffering from?
global ischemia
How does a global ischemia affect neuronal populations?
They cause a loss of neuronal populations.
Neurons present within the same vascular position and juxtaposed to each other may be selectively vulnerable or resistant to insult.
As blood flow is reduced via an ischemia, how is energy metabolism affected?
Energy metabolism is decreased. This causes a reduction in ATP levels and dysfunction of the ion pump.
A disruption via ischemia ultimately results in what to cells?
apoptosis
What is the Pasteur effect?
A fall in PO2 leads to enchanced lactate production. This reduces the pH of cells, causing depolarization and the movement of calcium into the cell.
It also causes the release of neurotransmitters.
What do NMDA and AMPA/kainate overactivation do?
Contribute to excitotoxicity.
During excitotoxicity, the loss of ion gradients causes the buildup of what neutrotransmitter in the extracellular space?
glutamate
During excitotoxicity, the activation of glutamate receptors causes the influx of what ion into the intracellular space?
calcium
Glutamate receptor activation causes the activation of what pathways?
cytotoxic intracellular pathways.
What is the function of calpain?
It degrates the cytoskeleton.
During excitotoxic injury, what is activated?
calpain
generation of NO and ROS
Damage to mitocondria
Phospholipase A2
You treat a stroke patient wih NR2B intravenously. How does NR2B prevent cell death?
It binds to the NMDA receptor, preventing the binding of death-associated protein kinase 1.
How to reactive oxygen species affect the membrane?
They react with proteins, lipids and DNA, causing structural and function changes in biomolecules.
How do reactive oxygen species cause cellular dysfunction and eventual cell death?
By reacting with proteins, lipids and DNA found in the neuronal membrane.
What barrier is dapaged in the brain during an ischemia?
blood brain barrier
The adhesion of leukocytes in this region cause vessel plugging.
What is one cause of ischemic apoptosis?
exposure to inflammatory cytokines
Damage to mitochondria
oxidative stress
deprivation of growth factor support
What does the activation of death receptor Fas promote?
formation of DISC, then procaspase-8, then caspases-8 and -3, which eventually activates tBID, which translocates to the mitocondria to execute apoptosis.
This is the intrinsic pathway.
The altered activity of protein phosphatase causes translocation of what?
BAD
It promotes the mitochondrial apoptotic pathway.
In the intrinsic pathway, a loss of calcium from the ER causes activation of what three factors?
caspase 3, 9 and 12
What organelles does the intrinsic pathway affect?
mitocondria and ER
What do caspases do?
Cleave key structural components of the cytoskeleton and nucleus, a characteristic feature of apoptosis.
What is infused into the tissue during thrombolysis/embolectomy?
Tissue Plasmogen Activator (TPA).
Reperfusion reestablishes circulation but with risk, may cayse fatal edema or intracranial hemoorhage.
What is DHA?
On omega 3 fatty acid involved in brain and retinal development.
It has been used in patients with ischemia and spinal cord injury.
What does NPD1 act against?
apoptosis.
It also promotes cell survival and inhibits brain ischemia.
