Blood–brain barrier 101 (tight junctions)

1:16:38>> Okay. All of that glucose, all of that oxygen, 20% is going to our brain. Okay. It's got about 400 miles of capillaries in our brain that is supplying energy to the neurons. >> Mhm. >> Now, all of that energy has to get through from the blood into the neurons. >> Right. And it has to go through something called the blood brain barrier. >> Mh. This is an incredible plumbing system that we have in our brain. Okay? It's different from everywhere else in the body. Everywhere else in the body, normal blood vessels, they carry blood. Okay? And they've got these like

1:17:19gaps. >> Mhm. >> Where stuff can go in, stuff can go out from the blood. So, you know, hemoglobin can go through, oxygen can go through, glucose can go through, little tiny metabolites can go through from, let's say, our muscles to the blood back and forth. >> The the junctions in the piping are loose. >> Mhm. >> Literally, >> there's there's like gaps. >> Yeah. >> In the blood brain barrier, the junctions are what we call tight junctions. >> Okay. >> Okay. These brain endothelial cells, which are the the cells that line the blood vessels in our brain, have tight junctions and they're so tight that 99%

1:18:01of large molecules and 95% of small molecules do not make it through. Not even glucose can go through unescorted. >> There are literally things called transport proteins that have to take glucose from the blood >> through a special kind of passage into the brain. >> It's like a clean room. It it the the analogy I think of it's like it's like flying regular blood vessels are like flying back in the day where there's no TSA. >> Yeah, dude. >> And then and then but the blood brain barrier is like TSA. >> Yes, it is. It is exactly >> take your shoes off. >> Yeah. >> Got to scan your bags. >> Yeah. Yeah. >> Random search. >> Random search. Come to the back room. >> Yeah. Exactly. Yeah. Exactly. Exactly. The brain is like because because the

1:18:44brain is like arguably the most important thing for our humans. Like there's a lot of security >> between what's coming in and what's going out. >> Yep. Which makes which makes sense. >> Totally makes sense, right? >> Um and >> if these bloodb brain barriers fail, if these junctions fail, the tight junctions, >> if they become leaky like with normal blood vessels, then that's going to lead to non-specific leakiness. We're going to get inflammatory compounds that come in. We're going to get cytoines. That's going to drive neuroinflammation and that's going to exacerbate any Alzheimer's related pathology. I see. I see. >> So now there's a new hypothesis here. Not the amyoid hypothesis but the vascular hypothesis. This is the

1:19:26hypothesis that says systematic vascular disruption >> caused by aging caused by high blood pressure. That's going to loosen up the capillaries in our brain. And that's actually a primary driver for neuroderadation. >> Okay. >> Yeah. So the the the idea is the the we have two sort of sort of uh thought processes here. One is this a myoid plaque accumulation >> is the driver of this neurodeenerative stuff. Then the other idea is that the the degradation of the blood blame barrier on on the capillaries the 400

1:20:07miles of capillaries in your brain >> is like the inciting incident that then enables a whole slew of derivative stuff like that is >> it's a precursor to the amoid stuff. >> Got ah that right got yes right like it's not just that the amoid piece is not connected at all. No, but it's not the first >> it's not the first thing. And perhaps there's something upstream that we can tackle, right? That we can put a dam on. >> Okay. >> Okay. And usually this stuff is a hurdle, right? Because the blood brain barrier structurally prevents most drugs from reaching the brain. Right. >> Right. We've we've heard about that like, oh, this thing can cross the blood brain barrier and then like the valuation goes up by a lot because it can cross the blood brain barrier.

1:20:48Right. People are trying to do like nanoparticles. You might have heard of like nanoparticles that go through the bloodb brain barrier. You can also do like sonic disruption where you like like send like high frequency sound and that sound disrupts the bloodb brain barrier. But it's like well if we're trying to fix the bloodb brain barrier, we don't want to, you know, like it's like a >> catch 22 type type situation. And this particular paper is leveraging that hypothesis to actually treat the brain by targeting that blood brain barrier itself. You're not going to pass through it. We're trying to repair the the plumbing. Yes. There. >> Yes. >> Okay. Yes. >> Now let's get into um this particular paper in this particular lab at UCSF. So

1:21:28they first started out by doing this technique called heterocchronic parabiosis. The idea is you take uh old mouse and young mouse and you join up their vascule, their blood. >> Okay. >> And so it's kind of like that thing on Netflix where like you know the old guy is getting like the >> Yeah, it's what Peter Teal's doing, right? Yeah, like the young person's blood. Well, this is like the the genesis of that. Okay. >> Okay. They did this in mice first. And the old mice that were exposed to the young blood showed neurological rejuvenation. So, new neurons, better memory. It was actually reversing the effects of dementia.

1:22:08>> Very interesting. >> Okay. >> The introduction of new blood was actually basically having neurological positive benefits. >> Exactly. And so now you can start thinking, well, okay, maybe other interventions could make the blood young. One of the easy things is aerobic exercise right? >> Like cardio. >> It's a potent intervention. It delays cognitive decline. And maybe that cardio and exercise is doing something else to the blood that is causing that blood to rejuvenate. >> Okay, I just want to pause really quick because I I'm tracking. So the idea is >> this uh uh heterocchronic parabiosis is this idea of a younger >> rodent

1:22:49>> uh has better the blood is >> the blood is better >> it's better. >> So if you're >> and it's like reversing all this like >> stuff. >> Yeah. >> And so if you put that younger rodent blood in an older rodent it makes the older rodent better.