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BIOL 4315 Neuroscience Tue Th 4-5.30pm - Neuroscience Lecture 23 Medical Cannabinoids and COVID-19 and CNS
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00:01 This is lecture 23 of Neuroscience, and Thursday are last in person meeting
00:09 that will be followed by uh midterm or final exam which is exam
00:15 It's non cumulative review. The following we ended last session talking about how
00:23 are accepted pharmaceutical medications that are made cannabis plants such as cannabidiol or T
00:35 C CBD combination that are planned And we also talked about synthetic pharmaceuticals
00:43 are basically made from chemicals in the . The Delta nine T H C
00:48 are through FDA approved prescription mechanisms that available to patients for very limited number
01:00 conditions. And we don't even have T H C CD D and the
01:08 is from the United States is only D for severe forms of epilepsy or
01:15 T H C. That's on a level. And at the same
01:22 I said that if you recall that and Delta nine T H C is
01:29 placed on schedule one of the D , schedule one in the 19
01:38 it's placed there as the most together the most dangerous other drugs such as
01:46 and to be placed on that schedule , the substance or plant or whatnot
01:55 no medicinal benefits is highly addictive and be dangerous. So now, despite
02:07 cannabis, despite these medications that are , there are cannabinoids and or plan
02:13 cannabis still on the federal level remains schedule one. And that's I think
02:19 a delayed reaction by the federal government probably will change in the next few
02:26 . So there are benefits that many smart people uh realize from research,
02:32 and scientific in the use of cannabis cannabinoids. We also discussed off,
02:37 don't have a separate section to discuss negative effects of cannabis. But I
02:42 that especially with Delta nine T H , it's pros psychotic potentially. Um
02:50 can be affecting an individual or a time depending on how the individual
03:00 It, it can be affecting that memory performance. So we talked about
03:07 use disorder, which is essentially a of addiction to cannabis. One in
03:15 or one in 11 users have that use disorder. And last I looked
03:21 the United States, I think 12% population or something like that use
03:27 So it's a, it's a fairly number. And we also talked about
03:31 Ais syndrome. And so the the pros psychotic pro panic attack effects
03:38 cannabis. And also uh a lot people ask me, well, I
03:43 this and it did this or it made it worse. I was expecting
03:47 to. And I, and when try something that is from unregulated
03:53 you tried something, you don't know it is, it's weed,
03:58 But you don't know the test It hasn't been run through H P
04:05 C. It doesn't come with certificates analysis from certified analytical laboratories.
04:16 So now we're here and we talk Delta nine T H C. We
04:24 about CD E and I also mentioned session about Delta eight and Delta 10
04:30 H C. And I said that are semisynthetic Annabi that are derived from
04:37 one from delta nine T H You can see this double bond here
04:43 between carbon line and down and it shifted between to d between carbon line
04:48 and nine. And this is uh D which has a different structure here
04:54 the uh cyclic versus the hydroxyl Uh And the point being is that
05:00 eight has been reported to be found , and planned. So some would
05:06 it a phyto Cannavino Delta eight. in reality, the Delta eight,
05:13 delta 10, the H H C is hexahydrate canna and all of these
05:21 of cannabinoids and Delta nine T H are now being sold through the hemp
05:30 and they're everywhere. I went to coffee shop yesterday and uh next to
05:34 coffee shop, it's like two miles from U f it's cool place.
05:38 a dispensary uh that sells all of different phyo cannabinoids derived from hemp in
05:45 concentrations. And so now we know this guy, we talk about this
05:51 , right? We know about CD , we talked about CD D.
05:56 we know about this guy. These are semisynthetic. OK. So
06:03 are semisynthetic that are typically derived from . OK. And we don't know
06:10 about the facts. We don't know about how they bind to the C
06:14 one receptors. Anecdotally. People report C B one receptor binding level is
06:21 and as far as activation when it C B one receptor, but the
06:25 properties of how long it binds to receptor are known. Furthermore, what's
06:31 not known is that there is a of research with Delta on Delta nine
06:35 H C. Um A lot of is showing that it has bad
06:40 showing that it has good effects. Delta nine T H C for
06:44 is proconvulsant in 10% or so. all of the studies that tried to
06:50 Delta nine T H C to stop , it ended up making seizures
06:55 So it's instead of anti seizure and convulsant delta nine T H C in
07:01 instances with some uh syndromes can be . So that 10%. So
07:09 but they've been studied nonetheless for a time. Delta nine and CBD these
07:17 and anodes, they haven't been Plus how they're prepared is really not
07:21 . Typically, it's uh passed through acidification process. Uh and sometimes it's
07:30 clear if there are any contaminants that still remaining after it goes through this
07:36 . Basically. So buyer beware when pull up next to the gas station
07:41 you see Delta Eight is sold Delta 10 or something like that,
07:46 guys now learned all of these things that will help you navigate through the
07:54 . There are a lot of different . So we just talked about major
07:58 , DH C CV D CD There's CV N CDC CV D
08:03 CBD G, we mentioned that there's 100 15, over 100 in general
08:08 cannabinoids. We don't know if all them have biological activity. We don't
08:15 uh most of them are non psychotropic nonintoxicating like CBD for example, but
08:23 are, and we don't know a about their interactions and which plants and
08:28 strains. This is what somebody is to figure out a lot of geneticists
08:32 a lot of growers from the botanical . And from the growers perspective,
08:38 molecules can you express can this plant ? And so they find plants that
08:43 . For example, CBD D, plant may have 7% of CV D
08:49 it may have 0.1% of CD D . So it's a minor cannabinoid phyto
08:55 rare phyto cannabinoid. And then somebody uh another strain and they find,
09:01 , this is CD D D is 1%. So then they breed that
09:07 to try for that plant to increase percentage of the cannabinoid. So it's
09:11 done with T H C. It's done with CD D. It being
09:14 with other minor cannabinoids and minor cannabinoids in need of research. We really
09:21 know much about their medicinal properties or of these different cannabinoids. And as
09:27 as their interactions with our human body the cannabinoid system in controlling or helping
09:34 specific conditions. Yeah, turbines will talk about aromatic molecules. Remember the
09:41 mass when you smell the lemons, citrus, when you smell the
09:44 when you smell the globes. So have all of these different structures and
09:50 also have different functions. So the in the middle better carry a filling
09:56 ayin that is found in gloves that found in hops. It is also
10:01 in cannabis plants. This is a CV two receptor against. So some
10:10 these aromatic molecules now you can see to cannabinoid receptors. What does that
10:19 ? So when you inhale, when smell something, it's in the brain
10:23 bind to cannabinoid Reuss, they're actually re suris in an olfactory circus.
10:30 if you adjust it or if you it into the lungs, then definitely
10:34 can have an effect on the two receptors in the brain and the
10:38 because as you saw, it's distributed the body. Uh Liu is another
10:47 is found in lavender and cannabis plants we smell cannabis plants. And for
10:56 lot of people, the smell, a lot of people, the stench
10:59 cannabis plants, whatever way you view is, we're smelling TPS because Dennos
11:08 a lot of carbons in them. . How many carbons are you
11:15 And the structures that have over 20 typical in their chains? Do you
11:26 when we talked about olfactory system? we said that we don't have reception
11:30 these long carbon chain molecules. So cannot smell cannabinoids. But when cannabis
11:38 , it's because it has a lot turps and it has a lot of
11:44 which would be found in lemon and cannabis plants will smell like lemon and
11:48 will smell like lavender and others will like gasoline or earth and others will
11:53 like skunk. So it's a variety different turps. And these turps actually
12:01 to both the medicinal and potentially the or intoxicating effect of cannabinoids as
12:08 especially if they're inhaled. Yeah. these turbines on their own have medicinal
12:21 . And what I would like for to pay attention to is not all
12:28 the things I want you to remember little is analgesic as you're living onto
12:32 . I want you to remember this as ace inhibitor. Do you remember
12:42 we came across? Ace inhibitors when studied the cholinergic system, acetyl coa
12:50 down acetylcholine and Alzheimer's medications were there were a set of cholester inhibitors
12:59 colonus inhibitors. And so this urine in a similar way essentially as some
13:07 the mechanistically, I'm not saying it's drug or a medication for Alzheimer's
13:12 but it has the same mechanism of on a cellular level as the Alzheimer's
13:18 did. There's even this thing in in, in Japan, it's called
13:23 forest therapy. People walk around and smell these coniferous plants and they relax
13:31 they say that it's really affecting their . And so obviously, it's affecting
13:36 mood and if you ingest and inhale , it's probably also going to affect
13:40 memory because we know that's important for for a memory system, the acetyl
13:46 system because that's one of the symptoms Alzheimer's disease is loss of memory due
13:53 loss of acetyl coli neurons, So globally, we have different medical
14:01 programs. We have this pharmaceutical program we already discuss Marinol Tex pharmaceuticals.
14:07 of them are national, some of are international. We have national cannabis
14:12 which are medical cannabis programs such as Germany or Canada or Uruguay or
14:19 So it's, it's spreading through the . The example in Germany is you
14:24 cannabis, flower buds at the So you have a prescription from a
14:31 , I think for any condition and go get your medicine at the pharmacy
14:35 it's health insurance subsidized, meaning that a plan, right? That maybe
14:41 insurance takes care of 40% of the of your cans. Now in the
14:46 , Canada programs are regulated by each differently. Massachusetts and Swan Texas is
14:52 one. Uh, and in those , patients don't have any health insurance
14:59 . So it's all out of pocket for very expensive products. Then they
15:04 be exempt exempt from now paying 20% tax on these products. As maybe
15:10 adult, the recreational users would have pay because the states would have two
15:16 , medical, you don't pay as tax, recreational, you pay more
15:20 , then you are more limited to type of products you can pro uh
15:25 and use essentially. So adult use recreational cannabis is present in the
15:32 in the United States, in many States, in the United States.
15:35 don't know the number now and nationally Canada, Germany just legalized it.
15:41 Canada, it's province regulated. So will regulate it in one way and
15:46 regulated by the state 9 to 5 Mont. So this would be in
15:51 Montreal on the, on the Quebec , on the, on the west
15:57 . Uh in Vancouver and British It's completely different. It's completely different
16:02 . It's the same country, but available uh for 18 and over some
16:09 , 21 over some provinces restrict a of it, others control it by
16:13 province governments. Uh Germany just passed adult use law which will allow individuals
16:21 grow their own cannabis and to go use cannabis in the social clubs.
16:27 uh this summer in Germany is gonna probably hundreds if not thousands of knock
16:34 the door, social clubs that open where every family member is growing three
16:41 . And so you need more cousins grandmothers to, to be registered to
16:45 flat. So you can grow more . So everybody controls it differently.
16:50 , it is full taxation that you through these programs. This is the
16:55 from 2021. This is old laws changing. Even Kentucky passed a comprehensive
17:02 uh use program, comprehensive medical cannabis . So it's going to turn way
17:08 green. Now, Texas will still what is called CBD low T H
17:13 program. And so we're gonna focus Texas but the darker the colors,
17:17 more open is the program uh with use uh Oklahoma, New Mexico has
17:25 adult use program. Um Colorado has use program and so on. There's
17:31 standard in the whole industry, there's no standard. Even if you go
17:37 these CD D shops or hem the advice that you're gonna be given
17:44 gonna be by this person who's behind counter, they call them but tenders
17:49 , D, tenders or something like . So when I go get my
17:54 for fun at the bar, I a little bit of this and that
17:59 that and I decide typically you kind do it with these products. They're
18:03 , you know, and then if is sensitive to canna, no,
18:06 know, something can happen in the like they fall asleep on you.
18:12 , so what do you do? you take the advice of the
18:16 you know, what is their level education? They probably know less about
18:22 than you will after taking this course they're gonna give you advice. This
18:26 , yeah, definitely from for Yeah, that's the one you
18:30 and, and then when the, know, when the consumers are
18:35 they're buying high concentrations of products thinking this is what is going to be
18:40 beneficial either medicinally or from the the perspective. And it may not because
18:47 you're looking just the concentration of one ingredient like CBD or T H
18:53 uh these preparations a lot of times have to use C CD D CD
18:58 , a lot of Turpin in them . But there is no standard in
19:03 the products are sold. There's no standard. There are, there are
19:07 standards for medical cannabis programs that are by state and then for him
19:14 it's kind of like a little bit a wild wild west right now for
19:17 far as regulation and what is being and how, and, and for
19:21 reasons. So, at the same in, in the United States,
19:28 have what are called unicorns. Unicorns companies that are worth more than a
19:34 , such as, for example, uh this company on top Duchy was
19:41 at $4 billion. And what they is they sell and have delivery services
19:48 you buy online and they process your card and they show up with a
19:53 delivery package at your door. And is both for medical and recreational
19:58 And here in the state of Texas medical programs, there are also deliveries
20:01 door to door basically from dispensary to patient's doors. Welcome to Texas where
20:09 are now today in Texas is 1% C limit in medical cannabis products.
20:17 only in ingestible forms. So they're gummies that we discuss and oil,
20:24 of them are sublingual. So not effective, right? We talked about
20:28 most effective ways to deliver these actives the brain for our purposes. And
20:35 tell you why. This is also to this program is by inhalation into
20:39 lungs or suppositories. But that doesn't in the existing program. Here,
20:45 are two licensed, uh, three uh, companies and two businesses that
20:50 operating. There is one of the who is in the heights here in
20:55 . Uh and it's sold at basically T E C which is 10 mg
21:01 DC per gram. And this is quick, pretty significant dose. Do
21:04 remember what Marinol was at? The ? I mentioned it was 2.5 mg
21:11 tablet. So this 10 mg of H C in some instances can be
21:17 mg per dose if, if it's weight by weight. Hemp farm bill
21:25 0.3% T H C in hemp So this is very strictly regulated.
21:30 have to compete, you have to business, you have to have D
21:34 S supervising operations and this is kind a more open and available. It's
21:39 mg of T H C per But guess what if you have a
21:45 g product and it's controlled by how much T F C is gonna
21:51 in five g? 15 mg. that's what I explained on the radio
21:58 when I was on my way here , to school on N pr that
22:03 these hump programs, the producers will these products 25 mg 78 g chunks
22:10 gummies uh in the hemp products. then these guys will be limited to
22:18 maximal doses, which is now going be 10 mg right now. It's
22:22 to 20 mg. It we will back to 10 mg again. So
22:27 1% DC. It also is an component in Texas. There's a law
22:34 talks about institutional review board which allows of these products that got me some
22:41 with medical schools and universities. And is one of the pathways of bridges
22:46 I'm interested in building between the industry the academia and the research and medical
22:53 . That again, I said we study these chemicals and order them online
22:57 catalogs that are synthetic T H C CV D. But we cannot really
23:02 real dispensary products on real human beings a real university or clinical setting to
23:07 address? Does it really help or it a placebo for many of these
23:11 ? You know, so, but , it's interesting because a lot of
23:15 don't have this I R B component far in two years, nobody has
23:21 on this pathway. It's very Um Maybe we'll be able to,
23:27 , to do that here at the of Houston. Who knows we,
23:30 , we're trying. So this is compassionate use program. That's what it's
23:35 in Texas tea Cup. Texas compassion programs. Look at all of the
23:42 . It started in 2015 for seizure and severe disorders in particular, severe
23:50 epilepsies such as Dr syndrome and the had to fail on two other medications
24:01 they were allowed to have a uh that point half a percent of T
24:07 C preparation in 2017 when it became factor. So it was one condition
24:15 , in 2000 16 and 17, believe there were like 25 patients in
24:22 uh since 2021 and since 2019 and 2021 this has been expanded to look
24:32 all of these neurological conditions. Uh Alzheimer's autism, not any cancer,
24:40 traumatic encephalopathy, Parkinson's peripheral neuropathy, is peripheral neuropathy is damage to the
24:49 in the periphery. Like if you a broken arm and you can feel
24:54 your fingers or something, you have neuropathy that was qualified as a patient
24:59 . PTSD specificity, seizure disorders, neuropathy, dementia, epilepsy, multiple
25:05 , muscular dystrophy, and over 100 neurodegenerative disorders. In this legislative session
25:14 Texas, they're gonna add chronic pain this list too. So currently in
25:19 , there are over 50,000 patients next . It's gonna be over 100,000
25:28 I have a crystal ball and another years is gonna be over half a
25:33 patients even through this limited program. by the way, this limit of
25:39 T H C is gonna get lifted you can imagine uh I went to
25:44 hearing for the congressional Public Health and here in, in, in Austin
25:51 patients stood up and said my condition not allow me to swallow things.
26:00 need 200 mg of T H C my condition how much of the product
26:07 you taking? 20 g of the ? 20 mL of the product.
26:13 I barely can swallow my industry and no other route really to deliver
26:19 Number one. So they need other , depositories, they need inhalation
26:25 That thing is even if you can it, 20 g of something,
26:33 know, 20 g of oil, five tablespoons of oil or something like
26:38 every day or guney that has other in it for your body to process
26:45 digestive system. Again, it's it's difficult. So at this junction right
26:53 , this year, they're probably gonna that percentage of T H C and
26:58 gonna leave the dose to 10 But that weight of that dose doesn't
27:04 which means you could have a 50 product with 10 mg of T H
27:09 per dose and it could be a grain of rice. And now those
27:13 that we have needed to consume 20 , they can now just consume 20
27:19 of rice, equal one g like little tablet form or something like
27:24 So that's making progress, making We're still behind a lot of other
27:28 where, you know, people just out and party with, with
27:33 But this is my warning, you , look out for this semisynthetic.
27:38 all over not knownn very well. know more about this and this and
27:43 is a program and if you have in your family, in Texas that
27:48 kind of a fed up maybe or get help from pharmaceuticals. There's a
27:53 you can explore a department of public with them or for them, how
27:58 register to be a patient and it all with the supervision of medical
28:03 So you cannot just like I'm gonna online, you know, you have
28:06 have a condition. So if you one of these conditions, that means
28:10 have been diagnosed, you have to a proof of your diagnosis from your
28:15 , then you contact the physician that a part of the tea cup and
28:21 you prove that you're this, that have this condition and they will work
28:25 you and they will work with you doses, they will work with you
28:29 product and stuff like this, So it's not just like,
28:32 in many other states, it is non medical. It's more like medical
28:39 recreational purposes with the qualifying condition is headache who hasn't had a headache in
28:48 life. Everybody is qualified. So a qualifying condition is headache and
28:53 you get a card and that's And the doctor doesn't recommend you anything
28:57 then you just go and shop for just as you like, you
29:01 So in, in Texas, this is actually has real medical aspects that
29:06 I I like it's restrictive, it medical aspects. And I think that
29:10 should uh change the laws in general cannabis in Texas because it would help
29:15 lot of people uh uh for medicinal and also prevent a lot of criminal
29:23 that is associated with it. All . So, and by the
29:32 in some states and in this cannabis is decriminalized in certain counties.
29:40 Harris County has cannabis, decriminalized cannabis possession, not if you're a
29:47 or a grower, but if you're with possessing cannabis, small amounts up
29:53 three ounces, which is a huge . Uh uh The officers in Harris
30:01 are supposed to uh give you a and tell you to take the course
30:07 learn about sobriety and stuff like So on the first offense, I
30:12 know on repeated offenses what happens. so anyways, let's talk about
30:19 Now we have a little bit of left to talk about that. Happy
30:22 20. We're with cannabis uh COVID-19 the path of physiology was still experiencing
30:31 still discovering things we're still experiencing effects COVID-19. Some of you walked up
30:37 me in this or the other section said my so and so or me
30:43 my cousin kind of still smell anything it's been three months or it's been
30:49 year, what's going on, you , so this is what we're talking
30:54 and it's not just a anosmia loss smell as a consequence. Of a
31:00 infection, but a lot of downstream complications that can stem from it.
31:08 for the viral entry, we talked this cry form formation, the
31:13 this is where the olfactory receptor, the optic nerve, uh olfactory nerve
31:20 in. Ok. And it can there. So you can have infections
31:26 the brain through viremia. You have in the blood. You, you
31:30 touching dirty counters and wiping your face you got infected. It's in your
31:35 system, it's in your blood. gets the viral load is is is
31:39 , it gets into your brain nasal . So you're right and you're essentially
31:49 it, inhale it in the It may not get in your
31:53 Why? Because from the lungs, gonna go into the blood and to
31:58 into the brain, it has to through the blood brain barrier and it
32:02 not always. So now, hypoxia , if you have lung infection,
32:10 you are typically having breathing problems. oxygen levels is one of the things
32:17 measure is oxygen levels right away. the pandemic started, everybody was trying
32:22 get these oxygen sensors because the minute felt a little bit queasy or
32:27 you know, they thought they had . So they put the little voltage
32:30 on their finger. And if you serious infection, you have problems with
32:38 , proper oxygenation. So they have hypoxia could be low level depending on
32:43 viral infection. It could be pretty hypoxia which will compromise the blood brain
32:50 . When the virus comes in, has to bind to a two receptors
32:56 is angiotensin converting enzyme to receptor. present everywhere and we'll talk about the
33:04 epithelium. Uh but it's also present the center of the peripheral nervous system
33:09 our purposes. That is important in . The function of uh of that
33:15 is to control blood pressure. anosmia, and if you have a
33:24 receptor, you are likely to be . And so here we have uh
33:30 odorant molecules, we talked about odorant . But you through the through the
33:35 cavity, can anybody can in inhale airborne viruses. And the first thing
33:43 they can encounter are the CIA of cul receptor neurons, but they don't
33:49 a ST receptors. Instead, these cells, these large long green cells
33:56 are called sustentaculum cells. These CYA have a two receptors. There are
34:04 some progenitor cells here and they also a two receptors. And because here
34:12 uh essentially these salts are facing sort with the mucous layer. They're also
34:19 to infections by COVID-19. But that not going to result in anosmia.
34:27 have to have an infection or factory neuron O R N, which has
34:33 two receptors. How does this infection ? And one of the hypotheses is
34:40 you have essentially this trans cellular infection virus essentially crosses from one cell into
34:51 other cell and we'll talk about it little bit later. So if the
34:59 gets into the brain, it can neurons and can infect astrocytes because they
35:05 h two receptors. Ace two receptors also found in the endothelial cells and
35:11 lining between the blood capillaries and the . And so if there is a
35:19 or compromise of blood brain barrier, the blood brain barrier gets inflamed,
35:25 becomes loose, these molecules from the will start crossing into the brain is
35:32 infecting neurons and glia. And if recall, it's the aside and feet
35:40 are part of the uh the blood barrier um right here that surround all
35:48 the micro capillaries in the brain. . So let's say uh you have
36:00 an infection and if you have an in the blood, so let's look
36:09 the top. There are three theories which this virus COVID-19. SARS COV
36:17 gets in to the brain tissue And this is a larger figure and
36:26 is the figure that has all of descriptions so that you can uh read
36:33 of the details. Although these articles those figures that you're seeing here in
36:39 lecture uh in in your lecture there's one folder for COVID-19 updated and
36:49 has two or three PDF. So you're interested in rereading this in greater
36:56 , than just the figure led like paragraph or two on that figure,
37:01 welcome to open those materials. But , if you enter through this
37:11 you are not concerned about blood brain . OK. So if you enter
37:18 the olfactory epithelium, the infection is the receptor, neurons and cellular infections
37:25 the brain. Now what happens if in the blood? So following a
37:31 tract infections is virus is going to in the blood, is going to
37:41 these endothelial cells with the interaction of two receptors which they contain.
37:50 And if they infect essentially these endothelial , the tide junctions that exist,
37:58 normally, they become loose. And means that the control of what gets
38:06 from the blood into the brain has very loose gate now. And that
38:12 that the virus has a much easier to get in through uh through uh
38:22 the brain. Uh Now you have cellular migration, h two receptor
38:35 endothelial cells, infection of astrocytes infections of other glial microglial cells,
38:41 of neurons paracellular migration where it does infect the the the cell but rather
38:55 through the side junction and just infects and glial cell sub types. And
39:03 third mechanism is what is called the horse where the macrophage, right?
39:10 now you what is microphage is, here uh is the the the the
39:16 response. Now, macrophage engulfs this and this microphage has the ability to
39:27 into the brain and kind of a like innocent like Trojan horse of the
39:33 horse story, which was built from . And then in the Trojan horse
39:38 , what happened is inside that giant horse, it was an army.
39:44 . So they got the army and the gates of the city under the
39:51 of the gift of the Trojan So it looked innocent but inside there
39:55 an army that destroyed that city. this is the same Macri brings it
40:01 . Oh, you're one of We understand and then boom. Now
40:04 got this bomb inside of me called virus. We're all infected.
40:13 So this is another neurological involvement in . The potential mechanisms to review that
40:20 attached to in that same document fold I was discussing uh if you have
40:27 system activation and endothelial damage, what is if you recall microglial cells,
40:35 control cytokines and cytokine release in the . And so, first of
40:40 there's gonna be an increased systemic cytokine and then there's gonna be an increased
40:45 of cytokines and increased inflammation and sometimes inflammation in the brain contributed by the
40:54 cells because it will be overproducing these and it's called the cytokine storm in
41:01 brain of the body. So, of pro coagulation factors, COVID-19,
41:16 two is emerging more and more. as a blood and blood vessel disease
41:31 potentially a coagulopathy. Because if you up the lungs and clog up the
41:41 vessels, what happens if you you create thrombus, you block up
41:47 blood vessels. If you have a , the blood will not flow.
41:52 the brain area that has the thrombus the blood vessel will not be getting
41:57 supply and the nutrients or even the blood clot can bust the blood
42:05 causing a stroke. Ok. So can plug up and then eventually can
42:13 lead to the stroke formation. So it without even entering into the brain
42:24 . Now, we have a possibility very high viral infections circulating in the
42:30 and plugging up causing thrombosis in the vessels in the body and potentially in
42:36 brain. So now, of you have the direct viral invasion of
42:45 and cerebrovascular endothelial cells from the Ok. So here you have the
42:53 damage. Here, you have the endothelial damage as you ruin the entire
43:00 . Here, it's sort of that uh trans cellular migration, you infect
43:06 cells and then eventually what it leads really leads to neuronal necrosis and neuronal
43:15 , which is neuronal cell death. high viral loads of SARS called two
43:23 into the brain tissue will cause neuro , neuronal loss through these two
43:30 necrosis and apoptosis, which is So that as we talked about,
43:38 focused on C N S and C S. The main symptoms are headache
43:44 vertigo. Now, you understand these better hypodense areas and C T
43:49 you remember with C T scans are pomography scans. So they are like
43:54 x-ray. It typically is used for , but it can pick up the
43:58 in density. So the tissue can up cancerous growth and such. So
44:03 is a differences in density in C in the brains following infection and
44:10 The main symptom is headache and Major symptoms of stroke, meningitis,
44:20 , chronic encephalopathy, the hemorrhages. , hemorrhaging or bleeding essentially in the
44:28 , the C N S, there's conclusive treatment. Although there's a lot
44:32 different treatments, this is kind of and a lot of different hospitals will
44:36 their own treatment management and recovery protocols the significant C N S infections that
44:43 lead to these may, may major . And on the peripheral side,
44:49 still don't want you to, we're going to talk much about G BS
44:55 anoscopy and A is the main Um I may ask you that question
45:02 but mark the correct answer for an this time it's gonna be a
45:10 Ok. So we have the pathophysiology the peripheral system. We're talking about
45:16 chemo sensory dysfunction. So loss of loss of taste virus reaches globs and
45:22 cells in the nose. Virus reaches and inflammatory response. There's chemosensitivity,
45:38 have viral entry into the brain. , if this virus goes in into
45:43 nasal cavity, it can reach the in the olfactory bulb via the nasal
45:48 , essentially. And then it can uh neurons and and the the cells
45:56 or uh viremia leads to virus to circulation. So, a lot of
46:03 that comes from, from inhalation from lungs. And now when there is
46:10 lot of infection, there's gonna be of blood brain barrier ox on brain
46:18 . And when you have dying there is going to be intracranial pressure
46:24 rises and pain, it's very And you may have cerebral edema or
46:31 clotting area. Uh uh coagulations in brain. Uh cerebral may compress the
46:40 stem and alter respiration. Remember, stem has nuclei that are responsible for
46:46 body functions. And if you have of these changes in the pressure,
46:51 pressure, if you have changes uh and the cerebral edema, which is
46:58 , ok. If the brain tissue , that brain tissue cannot go
47:03 it's going to start pushing on the bones and surrounding tissues. And if
47:09 nuclei swell, that are responsible for body functions, they can start essentially
47:15 their functions, affecting breathing and heart . The adverse immune response is another
47:22 viral invasion could trigger cytokine over You have cytokine storm which leads to
47:29 acute necrotic encephalopathy and hemorrhages. hemorrhaging of the blood here, it's
47:34 swelling, edema is a swelling. could be because of the dysfunctions of
47:39 blood. But it could be because the inflammation in general in the
47:43 You have swelling of brain tissue And here you have hemorrhaging or the
47:49 blood uh spillage problems and coagulation and uh respiratory stress loss of oxygen in
47:59 lungs. So if it comes in lungs, respiratory stress, multisystem,
48:04 failure, oh boy. So the is not the only thing that is
48:09 to oxygen loss. If there's significant loss in the systemic, you can
48:15 a kidney, systemic failure of of organs, basically uh leading to neural
48:23 in the brain. So if somebody breathing for a while and you have
48:28 and start killing cells slowly but potentially again to hemorrhaging and acute neron
48:38 Yeah, neurological abnormalities have been described about 30% of patients who required
48:46 And I think I discussed that But I'll remind everyone that the more
48:51 the illness, the higher the percentage people uh uh experience neurological abnormalities,
49:02 and encephalitis. Remember it's an infection inflammation can cause swelling can cause cell
49:11 . Nice accurate necro necrotic phal You heard of encephalitis, probably encephalitic
49:22 and if they bite you, you get encephalitis and even end up in
49:26 emergency room unless you're vaccinated for certain and such. And this happens in
49:32 types of uh uh locations geographically, wise. And also certain times of
49:38 year, typically when there's a breeding for ticks, uh post infectious neurological
49:47 . Uh It's not uh doesn't sound bad but is hemic stroke sounds really
49:55 . So that stroke basically due to lack of oxygen due to lack of
50:02 supply. Um or uh are situations it's coagulation that busts the blood vessels
50:11 thrombosis, too intensive care related neurological . So a lot of people that
50:19 into intensive care and if they got , I think the it was like
50:27 and four were probably not gonna recover that procedure. And then to go
50:34 that is very difficult psychologically to be medically is, is difficult when people
50:42 their varied degrees of, you fear or, or uh or you
50:49 , other kind of a psychological or reactions to, to medical treatments.
50:57 But if you end up in intensive , it will also kind of have
51:02 heavy burden on you. Um can other neurological manifestations because you ended up
51:08 the IC U. That means that probably were intubated. That means you
51:13 lost oxygen for a while, probably some mild form of apoptosis or brain
51:19 death. Ok. And that recovery be very long. So once you're
51:25 the tube and you're breathing on your , that recovery can be very
51:29 Why do some people lost sense of ? For just a, a few
51:34 or a couple of days and others recover it for a long time.
51:39 think it also has to do with several factors. First of all,
51:45 amount of virus, the viral were you infected with just a little
51:50 of virus or were you eating it of it in the cafeteria? You
51:58 , and inhaling it. Number number two, your immune response.
52:06 it's not necessarily whether you're weak or immune response, we have a different
52:13 that our immune system is also reactive different things that we've been exposed throughout
52:19 life. How we would develop to that we're exposed during early development is
52:24 all the kids get sick all the and bring all the runny noses and
52:29 the crab back home to their parents the first like 23 years. They
52:34 to daycare or elementary school. so immune, this is all stimulating
52:41 immune systems, all building their immune and they may not have been exposed
52:45 Simula or the same type of, , or in this case, Sim
52:50 Mogan, because SARS CO two has been around, it's called COVID-19 in
52:57 you don't remember because it's reared its head in 2019. But it's been
53:03 someplace. We don't know if it's around in some labs or it's been
53:07 in some animals, but it's been . Right. And, uh,
53:13 so the immune response is important. then depending on the amount of the
53:21 and the immune response, you may a loss or greater loss of these
53:28 receptor neurons and they will regenerate. hair cells will not regenerate, but
53:37 il endings that will regenerate, it have to do them with the overall
53:44 , the ability for the system to recover it could be a systematic
53:49 too. So there's no really good of why. But typically the higher
53:55 viral load and the weaker the immune could be related to age. For
54:01 , like in elderly people, this a problem as I was searching for
54:07 information to add on this material. today, I came across some really
54:12 reading and I was reading and reading and I just uh didn't add any
54:17 new information. But what I was is really uh almost uh do you
54:25 we talked the, when we talked the factory system, we watched a
54:29 TED talk and the lady said that patients said if they still have the
54:34 of smell, it's a very strong of memories through the limbic system and
54:40 emotional response. And now I'm reading Alzheimer's and annoy is one of the
54:46 indicators of potentially being diagnosed with Alzheimer's . So in many cases, Alzheimer's
54:53 will actually lose that sense of smell . But what I was reading in
55:00 to what we're talking about is that seems to be maybe an A A
55:06 problem already that has started with Elderly people had very difficult time,
55:14 difficult time recovering their sense of And if you think about it,
55:19 is all about plasticity, this is about sensory. Remember about sensory
55:26 you deprive the eye of the you rewire the circuits. So then
55:31 the the stronger the problem, the the recovery in a way. And
55:35 has to do potentially with the wiring with the plasticity in the brain and
55:40 rebuilding of the synapsis and the connectivity the olfactory nerves into the secondary neurons
55:47 the olfactory bulb. Um So on uh slide, it's not our last
55:58 , but this is it our last on this slide, I'm actually gonna
56:04 to this slide here and remind you we started. OK. So this
56:28 the first slide for the lot of that you saw. And this is
56:34 be the last slide that I want to look at have to go through
56:39 whole semester. But knowing that you really understand way way more hopefully and
56:47 just in your short term memory, also in your long term memory and
56:52 hippocampi engaged. And then um it's pretty humbling the structure. And I
57:02 and that it is pretty humbling. talking about billions of cells, trillions
57:07 connections A I hasn't cracked the brains but it may be, but it
57:14 be, it may be learning a from the brains. It may be
57:18 of building circuits like we have in brain. Maybe some of them will
57:22 able to process things sensor information similarly how we do. Um Maybe there
57:29 be organoid and we will use what called organoid intelligence. It's artificial intelligence
57:39 groups or networks of cells that can together and interact with each other.
57:45 the future robots will be these almost like putty like organo that you
57:51 on the desk and then like runs little wire and it has its own
57:55 and it actually grows and it changes it has plasticity and it's not a
58:00 of plastic but it's like a putty something like that, you know,
58:05 it's a life. So uh right? Uh I wish there was
58:13 neuroscience and kind of a psychology in when the first avatar came out and
58:19 went to that enchanted forest and connected um of course, their tails right
58:30 , to the network in this enchanted . I don't know if you've seen
58:33 movie and they get like connected to whole, basically this whole ecosystem,
58:41 whole environment, they become one of . And I was just sitting and
58:45 was like, they're going to talk the brain neuroscience, neurons, synaptic
58:51 called it a through the, you , I was imagining all of
58:54 And then do, do, do, do, do,
58:56 do it, ended up a big up at the end of the
58:59 But they missed, I think an . But it's still very interesting.
59:03 is a changing world. We have reality surrounding us. It is becoming
59:09 prevalent. I would like to, you to think about what Doctor Ramachandran
59:14 with mirror boxes and think about, , can this be done with the
59:20 reality? Can't you rebuild human motion , and rehabilitation? Can't you get
59:26 of phantom limbs using virtual reality? this is all for you and for
59:33 future uh to, to reveal. . Thank you very much. Thank
59:41 for coming and being here. I see everyone on Tuesday for the review
59:46 and uh have a good weekend,
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