Term
Cellular Effects of Ischemia |
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Definition
•The primary trigger for cellular pathology is depletion of ATP.
•Three intermediate events facilitate amplification of cell damage
–Increased lactic acid
–Increased Ca+2 release
–Anoxic Depolarization
•Excitotoxicity
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Term
Ischemia and Ca+2 Influx Lead to.... |
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Definition
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Term
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Definition
•Excitotoxicity is due to increased extracellular levels of glutamate and aspartate.
•Glutamate (normally in synaptic terminals) is cleared from the extracellular space via energy dependent process that is compromised upon energy depletion (ischemia) resulting in an increase in extracellular glutamate.
•Results in opening of calcium channels which leads to Ca+2, Na+, and Cl- ion entry into cells and K+ leak.
•Multiple signaling cascades and enzymes are activated leading to membrane damage, inflammatory stimulation, and eventually cell death.
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Term
Modulation of Glutamate Receptor Activity |
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Definition
• Early studies of receptor
antagonists were unsuccessful
due to minimal efficacy and
side effects.
• However, advanced understanding
of receptor structure and function
have lead to development of
second and third generation
antagonists.
• Examples of selective ionotropic
NR2B antagonists are:
- ifenprodil
- eliprodil
• Modulation of Glutamate Receptor activity is an important emerging area
for stroke therapy/intervention
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Term
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Definition
-•Biochemical events in response to stimuli
–Production of arachidonic acid metabolites
–Degranulation and secretion of lysosomal compartments and oxidative burst
–Modulation of leukocyte adhesion molecules
•Recruitment, surface localization, and avidity/affinity.
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Term
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Definition
-•The ingestion of bacteria or other material by professional phagocytes.
–Recognition and attachment
•Opsinization- facilitate recognition (Fc IgG, C3b, etc)
–Engulfment
•Opsinized particle binding to FcR and/or Mac-1
–Killing or Degradation
•ROS generation via NADPH oxidase and Myeloperoxidase (MPO)- generation of HOCl.
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Term
Leukocyte Mediated Injury |
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Definition
•Leukocytes may also release cytotoxic agents into the extracellular space (e.g. frustrated or surface phagocytosis).
•Most important toxic substanes are:
–Lysosomal enzymes
–ROS/oxidants and/or reactive nitrogen species
–Productions of arachidonic acid metabolism
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Term
Irreversible Cell Injury Summary |
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Definition
-•Irreversible cell injury represents a committed step from reversible injury that leads to cell death.
•Acute inflammatory reactions and the generation of reactive oxygen species (free radicals) are primary mediators of reperfusion injury.
•Lethal injury may occur via necrosis or apoptosis, with cells in the ischemic core often undergoing necrosis and surrounding cells (in the penumbra) undergoing apoptosis.
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