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Blood brain barrier and vasogenic edema
- [Voiceover] This is a really, really zoomed-in schematic view of neurons and their supporting cells in the brain, and we know that without enough oxygen, let's say there's a clot right about here, and that's reduced the blood flow to this area enough to cause a stroke here, without enough oxygen, neurons can start to break down as a result of a process called the Ischemic Cascade, so that's obviously not good, our neurons breaking down, but to sort of add insult to injury here, there's actually a few other events that happen after neurons start breaking down during this stroke. Let's look at these subsequent events. We know that in the initial part of a stroke, a few minutes without oxygen will cause our neurons to start breaking down and dying off. We know that, but later, around a few hours later, certain components of the blood vessels that serve the area, they start to get broken down, as well, so let me actually zoom in on this blood vessel here. Let's look at a close-up. You might have heard of the blood-brain barrier, the BBB. It's essentially this extra layer of security that separates what's inside your blood stream, for example, any drugs or harmful little toxins. The blood-brain barrier separates what's inside your blood stream from your central nervous system tissue, out here, and this is to make sure you don't get any weird and not-so-wonderful infections or any brain injury from things traveling in your bloodstream. What makes up your BBB? What makes up your blood-brain barrier? I'll just briefly describe it. It's partially composed of endothelial cells, which are these neat little cells here that line the inside of your capillaries, so you can see they're really close together here to help prevent unwanted leakages of any little substances, then there's the basal lamina, which is sort of the endothelial cells underlay. It's pretty thick, and it also helps to separate stuff in the blood from stuff in the CNS. Then there are these tight junctions, and I'll draw some of these in here. Let me just draw in some of these tight junctions. These are little connector proteins that really tightly seal up any space between our endothelial cells, and that further restricts any unwanted molecules or substances from getting into the CNS. These tight junctions will prevent them from slipping between your blood vessel cells, these endothelial cells. The last component of the blood-brain barrier that I should probably mention are these astrocyte processes here, these astrocyte endfeet, and they actually don't have too much of a structural role in the blood-brain barrier, but they do provide some nourishment to these endothelial cells, so you could say they help maintain the blood-brain barrier, in a way. So why am I telling you all of this? Why am I telling you this stuff about the blood-brain barrier? Because about four to six hours after infarction, after you lose your oxygen supply to this part of the brain, your blood-brain barrier starts to break down, and two of the major reasons this happens is because of ischemia in the area, and because of an inflammatory reaction that's going on post-stroke. So what happens? The combined result is that your endothelial cells start to get a little bit leakier, and this basal lamina loses its ability to restrict some molecules, so it gets a little leakier, too. And really importantly, these tight junctions stop being true to their name, they loosen up a little bit, and they also become leaky, so you can imagine that this is just a disaster. Everything is supposed to be nice and tight, and now things are pretty out of whack. Let's see what ends up happening because of this. Proteins and water from within the capillaries, within the bloodstream, because there's often still a tiny bit of flow happening, proteins and water start to leak out at will. What do you think is going to end up happening now to the brain tissue here? Now the extra-cellular space here is going to get a little bit flooded with proteins and water, right? This so-called vasogenic edema, vasogenic means originating from blood vessels, this vasogenic edema adds to the cytotoxic edema that's already happening in the area, and that just worsens the swelling of this part of the brain after stroke. Why is this important? For one, swollen ischemic brain can't really carry out too many of its functions, so we want to minimize the time spent swollen as much as possible, and for two, it can result in a mass effect, which is where the swollen brain area starts to push on, or displace, surrounding brain tissue. Unfortunately I'm not referring to the excellent video game series called Mass Effect here, I am referring to a physiological mass effect. Let me show you one of the most severe things that can happen with brain swelling. You can develop what is called brain herniation. This is where the brain swelling gets so bad that a bit of brain gets pushed totally out of position. Say this bit of brain here gets pushed over toward the other side, or say this bit of brain here gets pushed down through this part of your skull where your spinal cord exits your head. Both of these are known as herniation of brain tissue, and they're both often fatal, so we don't like brain swelling at all. What sort of timeline are we looking at, then, for this swelling? The swelling that occurs as the result of this vasogenic edema, it tends to get worse over a few days as more water and protein leak out of the blood vessels in the area, and it peaks at roughly three to five days post-stroke, and then after that it slowly starts to resolve over the next few weeks as the protein and the water slowly get reabsorbed back into the circulation. This, of course, is a good thing, and it brings the cerebral swelling down.