Zaidi. Reperfusion, ischemia Flashcards
How much energy does the brain consume and what does it use it for?
20% of body energy
> used for transporters, heat…
Which is more highly metabolic in nature: gray or white matter?
gray
What can the brain use for energy consumption?
> glucose
glycogen: stored in glial cells
monocarboxylic acid
ketone bodies
What metabolic pathways are most commonly used by the brain for energy restorations?
>glycolysis >glycogenolysis >pentose phosphate pathway >malate aspartate shuttle (gluconeogenesis?) >TCA cycle
What 5 methods are availabe to study brain metabolism?
1. primary neuronal cultures in lab > glutamate excite, GABA inhibit 2. cell lines 3. isolated organelles or brain tissue 4. live animals 5.Imaging
WHat two types of imaging are used in brain energy metabolism studies?
- PET: using glucose and 2-fluoro-deoxyglucose
2. MRS: use NMR spectra with carbon 13 or radioactive carbons
What is focal brain ischemia?
- localized disruption or the brain due to a thrombus or embolus
- other areas are prevented due to the vast anastomosis in place
- the Umbra grows over time. interventions are used to stop spreading of penumbra (outer rim of ischemia)
Global ischemia affects teh entire brain due to interruption of blood flow, most commonly from an MI. What areas are most and least susceptible respectively?
- most: CA1 pyramidal cells, purkinje cells, striated neurons
- least: CA3 region and granule cells in the dentate
The brain is the main computer of the body, if you will. What biochemical operations are interupted when the brain becomes ischemic?
- ion gradients are disrupted from inhibited operation of active transporters
- -depolarizations, voltage channels open, uncontrolled 2ndary messengers
- increased lactate production and increased glycolysis
What main compounds contribute to excitotic injury?
-Overactivation of NMDA, and AMPA/kaimate
What happens when NMDA and AMPA/kainate are overactivated, and start excitotic injury?
increased glutamate leads to an increase of Ca ion levels. The Ca ion influx activates the release of neurotransmitters which activate proteases, disrupt the cytoskeleton, and damage DNA. The Ca ions will also activate caspase which activate cellular apoptosis
What is a major concern after blood flow and oxygen levels are re-established to an ischemic area?
The ischemic area is now able to generate superoxide free radicals from the ETC, that can attack lipids, DNA and proteins.
-There is also an increased number of PUFA, and Fe from degraded RBC
The blood brain barrier begins to degrade after 3-5 hours of ischemia, what helps this process and what symptoms become more of a concern with the degradation of the barrier?
- metalloproteins help damage the BBB, and leukocytes adhere to the area.
- Hemorrhage is likely to follow due to weakening of the BBB, and hemorrhage leads to release of cytokines, inflammation, and then edema
Explain the basic pathway of the extrinsic cellular apoptosis pathway.
- The activation of FAS moves to activate DISC and FADD
- -DISC activates caspase 8 which in turn activates caspase 3 which attacks important components of the nucleus
- -DISC activates BID to convert to tBID, and induces apoptosis of mitochondria in the cell
Explain the basic pathway of the intrinsic cellular apoptosis.
-Influx of Ca ions release excess amounts of cytochrome c, which activate caspase 3 which moves to destroy key components of the nucleus
