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Current time:0:00Total duration:6:35

Video transcript

so we know that when you have a stroke a blood vessel has been obstructed somehow and brain tissue subsequently dies so I want to show you some of the more important things that happen to neurons on a sort of zoomed in cellular level during a stroke so here we've zoomed in quite a bit and you can see it's really really complicated but actually this is still a pretty simplified view of the setup of cells in our brain I mean I've shown just a handful here but they're actually about a hundred billion neurons in your brain so these here in blue these are the neurons here and they're connected to each other so that they can pass messages between themselves and that allows the brain to control our bodies so these connections are called synapses now just quickly these here in green these are astrocytes these are really important cells in the central nervous system for example they reinforce the blood-brain barrier they nourish our neurons and they have many many other roles these here in this sort of dark blue II purple here these are oligodendrocytes and what they do is they give structural support to our neurons and they also allow our neurons to transmit their signals a bit faster of course these are blood vessels here little bits of capillaries so during a stroke when a blood vessels been obstructed and I'll just show a bit of an obstruction here a clot of some kind let's just look at some of the key events that happen on a neuron level a series of events called the ischemic cascade which is actually a slight misnomer because many of these events happen at the same time and they don't necessarily depend on each other to happen but you'll see what I mean as we get into it a bit so the ischemic cascade so without blood supply and therefore a lack of oxygen neurons will lose their ability to create energy in the form of ATP through aerobic metabolism so the neuron then goes on to plan B for energy protection it switches over to anaerobic metabolism which is what happens in the absence of oxygen but there's two problems with anaerobic metabolism in humans first it doesn't produce even close to the amount of energy that we need it produces about 15 times less energy than aerobic metabolism and second it produces a byproduct called lactic acid which if in high enough quantities it disrupts the normal acid-base balance within the brain and it can actually damage your neurons so we don't want too much lactic acid hanging around so I mentioned that the cell has less energy production happening how exactly does this change the cell's function well in a few different ways so let's start with the cell's membrane transport system so you got this the sodium potassium pump embedded in the cell membrane and what it does is it pumps sodium out of the cell and it brings potassium back into the cell and without ATP this pump stops working because it relies on ATP energy it relies on that ATP energy to do its job so sodium starts to build up inside the neuron because it's not being pumped out right and when water in this extracellular fluid this ECF here notices this high concentration of sodium in the intracellular fluid and the ICF the water rushes inside the neuron to try to dilute out that high concentration of sodium in the neuron so what ends up happening from there is that the neuron now starts to swell because it's being filled with so much water that's trying to dilute that high sodium concentration and this situation is called cytotoxic edema saito referring to our cell here toxic because it can kill the cell and edema meaning swelling and this happens early this is one of the earliest things that happens when there's not enough energy around what else happens well this sodium calcium pump stops working as well and you'll see how important this is it normally brings sodium into the cell and sends calcium out of the cell but if it stops working you end up with this ever-increasing amount of calcium building up inside of the cell and that's not really what we want for three major reasons so for one and up here we'll just call this excitotoxin II and and you'll see what I mean in a second so high calcium in the cell causes messengers like glutamate to be released from the end of the neuron so these messengers are collectively called neurotransmitters so you get this neurotransmitter release because of the high calcium and this neurotransmitter then diffuses off and sites other neurons because it's an excitatory neurotransmitter and so in their excitement these other neurons bring in calcium themselves which in turn causes them to release more glutamate and then this glutamate goes on to excite other neurons and so on so it's a bit of a vicious cycle of neuron excitement and neurotransmitter release that goes on which ultimately is a bad thing because over exciting neurons is potentially toxic to them the second reason we don't want too much calcium in our neurons is because too much calcium will activate degradation enzymes so the calcium will activate proteases which break down proteins inside your neuron and the calcium will activate lipases which break down the neuron cell membrane obviously that sounds pretty bad so you can imagine that if your cell membrane starts to break down all sorts of other ions and and harmful chemicals will enter the neuron and start to cause damage so that's no good and the third reason we don't want too much calcium is that too much calcium causes free radicals and reactive oxygen species to be generated so these are little harmful chemicals that lead to further neuron damage particularly of the cell membrane so I described cells dying by cytotoxic edema and by calcium dependent mechanisms but there's also another important way that neurons can die after a stroke you might be familiar with mitochondria the organelle responsible for energy production in the cell well with all these toxic chemicals swirling around in the cell and and the lack of their normal environment happening in the cell the mitochondria themselves start to break down and when they break down they release proteins called a pop tonic factors into the cytoplasm so they have a funny name a pop tonic factor is about what they do isn't quite as funny because the the cause the apoptosis cascade to happen and that causes cells to essentially commit suicide so there's a look at some of the major events that happen as part of the ischemic cascade and and three ways that cells might die as a part of the ischemic cascade