Dear all, does anybody has the idea about the major contributor to brain ischemic injury in different phases? i.e. In ischemia/reperfusion (I/R) model, the energy depletion values much in the ischemia phase, however, when the reperfusion start, oxidative stress begins to harm the brain cells. How about the fluctuation of immflammation along these two phases, then?
And, how about other brain ischemia models, like HIE, pMCAO, and etc. Thank you.
This is what is called as respiratory burst, during which there is activation of peroxidase enzymes that lead to increased level of free radicles that will cause a more harmful effect due to the leakage of these agents outside the neutrophils.
Depends of type damage i.e focal, global, total, partial, time of damage, phase, localization etc
Yes, actually I had a skype a talk with a person who shared a similiar opinion with you. He mentioned that usually energy depletion is the leading cause of ischemic brain injury, and inflammation may reach its peak 3 days after reperfusion, and decline later... ROS, however, may not be that important, according to his review.
but the increase of ROS depend of calcium liberation and the next nitric oxide generation, there are an disregulation of antioxidant homeostasis and the second increase of nitric oxide
Excessive accumulation of ROS, produciton of nitric oxide and disturbance of Calcium homeostasis (both in cytoplasm and mitochondria) are the main factors, since they both could harm the cells directly or activate apoptosis pathways.
Brain are the most susceptible organ to the damage due to oxidative stress b'coz neurons are rich in polyunsaturated fatty acids and level of endogeneous antioxidant enzymes (SOD, CATALASE, GLUTATHION PEROXIDASE) and non-enzymes (vitamine C and E) in neuronal tissue are low. After reperfusion several biochemical and molecular events occur as the xanthine oxidase which leads to production of ROS. These ROS cause cell membrane injury and finally neuronal cell death occur. Another events such as stimulation of arachidonic acid pathway, exitotoxicity by calcium, DNA breakup, caspase causes the neuronal death.
Excitotoxicity phenomenon caused by exacerbated glutamate release and NO production leads to necrosis of brain cell, being the most important events during ischemia phase.
In reperfusion period, the major villains are the reactive oxygen species that cause cell damage and push the cells into apoptosis.
The inflammatory process in the first phase is mediated by the microglia, which produce and release several cytokines, but when the flow is re-established, there is a strong migration of cells (neutrophils, at first) damaged brain.
With regard to the MCAO model, It's important establish the length of ischemia and reperfusion, and then you'll be able to choose the between phenomenon (excitotoxicity, necrosis, apoptosis or inflammation) in their analysis points.
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