January 20, 2014 (1)

Cytooxicity change in ionic balance membrane more

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Unformatted text preview: th Over release of Glutumate / toxic to the cells / killing the cells by apoptosis and necrosis/ mitochondria gets hit. Cytooxicity ( change in ionic balance /membrane more permeable allowing Ca and NA to come in the cell —cascade leading to cell death. Can occur following ischemic stroke Excitotoxicity, ionic imbalance, oxidative stresses, and apoptotic-like mechanisms. After ischemic onset, loss of energy substrates leads to mitochondrial dysfunction and generation of ROS and reactive nitrogen species (RNS). Additionally, energy deficits lead to ionic imbalance, and excitotoxic glutamate efflux and build up of intracellular calcium. Downstream pathways ultimately include direct free radical damage to membrane lipids, cellular proteins, and DNA, as well as calcium-activated proteases, plus caspase cascades that dismantle a wide range of homeostatic, reparative, and cytoskeletal proteins (Dalkara et al. 2003) Results of Ischemia -Immediate change in NA and Ca concentration across membrane/ 2nd messenger are activated /activation of proteins/as cell die with necrosis-release inflammatory agents microglia ( get activate)Il-1 and other agents Recovery-get rid of blood cloth( come cell recovery.. can go up to days .. years after the stroke Excitotoxicity and Ionic imbalance Lext of blood flow sets off a cascade of events that will cause T ack cells to die 1. Lack of oxygen causes the neuron to have reduced energy (ATP) 2. The Na/K pump that requires ATP to function will fail, allowing Na to enter into the cell and become depolarized 3. Allows calcium to rush into the cell and pumps are unable to transport it back out 4. Calcium in the axon terminal will cause more excitatory neurotransmitter glutamate to be released Effects of Stroke 5. Glutamate stimulates both the AMPA and NMDA receptors 6. 7. 8. 9. and allows more calcium to enter into the postsynaptic cells Over excitation of the cells causes the generation of harmful chemicals and enzymes (proteases, phospholipases) – this is termed excitotoxicity These enzymes degrade membranes and proteins Membrane becomes more permeable and more harmful chemicals will flow into the cell Mitochondria break down, releasing apoptotic factors into the cell Effects of Stroke • Restoring blood flow (reperfusion) will set off a cascade that leads to reperfusion injury • Inflammatory response starts – microglial cells start to phagocytise cells and engulf damaged but still viable tissue • Chemicals damage the blood brain barrier • Cerebral swelling (edema) occurs due to leakage of large molecules from the blood vessels through the damaged blood brain barrier restore blood flow to the brain-detrimental- sets of cascade reperfusion injury - microglia gets activated( releasing inflammatory ) we want to get rid of blood cloth-in case of stroke research ( minimize the reperfusion ( blood being restore in that area) injury) BBB gets broken down we use that...
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