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Multiple sclerosis pathophysiology

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Video transcript

- So here I have a brain slice of someone who's looking at you, and you'll notice that there's kind of this exterior portion and then there's this interior portion as well, and I've kind of color-coded both of them. We'll be, we won't be focusing too much on this blue part right here. So this exterior part is what we call the gray matter, and this interior part is called the white matter. And of course in this sketch, it's not actually gray and white, but if you look at a real brain, you'll notice that the exterior is kind of gray, and the interior is white. So what makes up the gray and white matter, well, if you'll remember, the brain is made up of about 86 billion neurons. Those 86 billion neurons are gonna compose the gray matter and the white matter. So let me actually draw a neuron over here. So here, you know, we have the dendrites, here we have the cell body, this is the axon, and this is the myelin. So you'll notice that I've kind of drawn the cell membrane in kinda the same color as this exterior. And the reason why I do that is because the cell membrane is what's gonna give that gray matter its gray color. So the dendrites and the cell body kinda have this cell membrane, and that's really what gives the gray matter its color. Now the axon also has some cell membrane, but the axon also has myelin, and it's the myelin that's gonna give the white matter its color. So the dendrites in the cell body are gonna compose the gray matter, and the myelin that's wrapped around the axon is gonna compose the white matter. To next, let's say that this person develops multiple sclerosis, and what we'll see are these lesions that kinda form throughout the white matter of the brain. That actually makes sense because in multiple sclerosis, the myelin that gives the white matter its color begins to degrade away. And the reason why it does that is because the immune system mistakenly recognizes the myelin as foreign, and attacks it. So how does the immune system actually make its way into the brain? Well, ordinarily, the immune system travels through blood vessels, so the brain needs to receive a lot of nourishment from these blood vessels, and the immune system is actually going to travel through these blood vessels. So what we're gonna do is we're actually gonna zoom in on a segment of the brain, so let's take a look at this particular segment over here. So here we have our blood vessel. So with this blood vessel, we're actually gonna have these cells that outline it, called endothelial cells. These endothelial cells will be really holding on to each other really tightly up here, like as if they're kind of holding hands really really tightly, and these points where they really hold tightly are called tight junctions. And these endothelial cells are kinda sitting on this foundation, right, kind of like a foundation of a house. So this red line that I've kinda drawn here, and we call this the basement membrane. Together, these will compose what's called the blood brain barrier, so the blood brain barrier. The blood brain barrier is a pretty special structure because it stops a lot of things from entering the brain, things that you really don't want to enter the brain. So for example you know, let's say we have a virus, and we really don't want that virus to enter the brain, because once it does, it'll start to do a lot of damage. So the blood brain barrier is gonna stop that from happening. It also stops your immune system from entering the brain. So you know, maybe you have a, maybe you have like a T cell over here, which is one of your immune cells, so let's say it's a T cell. It won't really be able to enter the brain, right, usually the immune system has some pretty limited access to it. But, in multiple sclerosis, these T cells are really able to squeeze past the entothelial cells and break through the basement membrane. And then that way, they can actually make their way into the brain. And so now, there really have access to a lot of the brain, and this is pretty bad, right, because this is actually an unfamiliar environment for that T cell, because it usually shouldn't be there. Now remember, in your brain, you have a whole bunch of neurons, right, so let me actually draw another neuron over here. So you have the myelin over here, and myelin has some pretty distinctive features on it, right? So it's gonna have some proteins that may kind of be at the surface of the myelin. The T cell may go to that protein and recognize it and say "hey, you know," "this for some reason doesn't look good." "For some reason, this looks foreign," "and I think that we should start to attack it." And of course, it's mistaken, because, you know, it thinks that it's foreign, but in reality, it's part of the body. So once the T cell kind of recognizes that part of the myelin, it'll start to go haywire, it'll kind of set off this alarm. So what it'll do is it's gonna release these chemicals called cytokines. And cytokines are gonna do a lot of different things. One thing they can do is they can promote the degradation of the blood brain barrier, so now the blood brain barrier becomes a lot more permeable to a lot more cells, right? So now, some more T cells can come in. The cykokines can also recruit other immune cells, so maybe we have a B cell over here, so here's a B cell, it's now able to enter the blood brain barrier, so now all of a sudden, you have these B cells in here, and they're gonna make these antibodies for the myelin. And once they make the antibodies for the myelin it's gonna target that myelin for further degradation. And then you may also even have some macrophages. And the macrophages are really gonna eat up that myelin and really physically degrade it. And then finally, those cytokines can actually be toxic to the myelin as well. So the cytokines can themselves degrade all that myelin. So now what you have is just a whole bunch of degraded myelin. So now we have a whole bunch of immune cells that are really clustered around a part of the brain, and when this happens, we call this neuroinflamation. So this is pretty bad, right? But, as it turns out, the brain actually does have a way of repairing itself. So, how does it do that? Well, let's say we have another neuron over here. So that myelin is actually gonna be provided for the neurons by these cells over here. These cells are not neurons, in fact, they're called oligodendrocytes, and when that myelin is degraded away, this oligodendrocyte will begin the process of remyelination. So it's gonna try to repair all that damaged myelin. And so this is great, right, this means that the brain has a natural healing process. And we call that remyelination. But, as time goes on, that remyelination actually becomes less and less effective. So the oligodendrocyte will really try to remyelinate the axon to the best of its abilities, but, it'll ultimately just become overwhelmed by the power of the immune system. And the immune system will be really persistent, right, these T cells will just constantly release all these cytokines, those B cells will always be around to release those antibodies, and the macrophages will always be around to actually phagocytize those, that myelin. So, ultimately what we have is this remyelination process that's being overpowered by the immune system.