VideoPoints

• ••• • •• • ••••• • •
BIOL 6397 CELLULAR NEUROSCIENCE Mon-Wed 4-5.30 PM - Cellular Neuroscience Lecture 22 COVID 19 and CNS
Help Tour
© Distribution of this video is restricted by its owner
Transcript ×
Auto highlight
Font-size
00:02 Our last lecture of Cell. And added some uh materials for you to
00:09 a couple of articles. I got couple of figures that are in
00:13 And for the life of me, couldn't find the article from which I
00:16 to hear presentation. I spent earlier one location searching for, for half
00:22 hour. I spent another 15, minutes. I just cannot find that
00:26 . I don't know what happened to . So I may correct it and
00:30 that article. If not, we'll discuss the figures as it is in
00:34 presentation without that particular article attached to . But uh if you have not
00:41 COVID-19 is still around, we're still a lot of bad problems from
00:49 Uh and a lot of these problems you get hospitalized are neurological complications.
00:57 if you have a regular infection, have your main symptoms of head
01:02 vertigo, coughing, runny nose all of that and you get over
01:09 . That's one thing. But if get hospitalized, that means you have
01:12 significant infection. And we've seen that one third of all people that been
01:19 have neurological complications and the worse the are for their like acute respiratory,
01:28 acute respiratory syndrome. The more the more likely they are to have
01:35 . So the way that the virus enter into the brain, which is
01:39 focus is first of all through the viremia and the blood, which treat
01:44 C N S. Uh We talked the olfactory system and these olfactory nerve
01:51 that are in the upper nasal cavity . When they get exposed to the
01:57 and odorant, they also get exposed infectious agents in there such as viruses
02:04 are airborne in particular. So, something through the no, inhaling something
02:09 the mouth may still affect the upper areas here. And the virus can
02:16 cross through these little holes called demonstrations the skull. The part a part
02:24 cribriform formation right here. These are little openings in the skull that will
02:29 for the olfactory nerve endings or olfactory neuron axons to basically go through these
02:38 in the skull into the secondary water bulb neurons. And so if the
02:45 can cling on or cross through these in in fact, no factor of
02:51 helium. And we'll talk about that subsequently the brain. Uh third of
02:57 , independently of how much viral load have, if there is respiratory issues
03:04 lack of oxygen or hypoxia, that compromise the blood brain barrier and allow
03:10 the viral agents to enter into the . And in general for viruses to
03:18 cells and take over their hosts, need a two receptors. So there's
03:24 angiotensin converting enzyme two. Uh there's intense in converting enzyme. Two,
03:31 receptors are involved in blood pressure but they're expressed everywhere in the body's
03:40 pressure regulation, but they're expressed They're expressed in neurons and blea and
03:44 expressed in different organs, the the kidneys, hearts and in the
03:50 nervous system. In addition to see two receptors are present on the endothelial
03:58 , endothelial cell lining, which comprises blood vessels. Also, they're present
04:04 the astrocytes as well as neurons. if there is a compromise of blood
04:10 barrier that you recall, it's the and feed that form partly the blood
04:15 barrier together with parasites. If there a compromise here of blood brain
04:21 you will see that substances can much pass out of the blood into
04:27 into the brain tissue. And once in the brain, it has multiple
04:32 of infection and invasion through neuronal cells different cell subtypes as well. So
04:42 a couple of articles that I I . Uh and maybe this is the
04:48 . Uh no, that's not There's another article I couldn't find about
04:54 in particular and this is a good 2021 description, neurologic symptoms occur on
05:00 , this is what I was just about. One third of hospitalized patients
05:05 Coronavirus disease. On these symptoms, encephalopathy develops in 1/5 of sphere
05:16 hypoxic encephalopathy, infection of the brain of the brain potentially can lead to
05:25 death. While ischemic stroke to strokes to thrombosis is common in one third
05:36 COVID-19 intensive care patients. So if in the hospital, one third will
05:44 neurological complications. If you in the U one third will have really bad
05:52 like a stroke, involvement of severe respiratory syndrome. SARS code two is
06:01 by several routes including hematogenous spread, entry through infected neurons or bacter nerve
06:09 epithelium. So besides entering through the of eli, it actually can enter
06:16 ocular Elum. So typically from touching eyes with infected fingers or something like
06:23 vascular and eli will already talked about the current blood brain barrier. So
06:30 is a good kind of a summary the main, main things that are
06:35 . And so this is a, diagram that shows your olfactory receptor sensory
06:43 here. Yeah, this on teams um so we have this uh
07:00 this is a where you have transsynaptic of Coronaviruses. So, coronavirus and
07:09 cavity can directly cross the transcript opening the ep bone to access the brain
07:16 perform transsynaptic retrograde migration using the vesical machinery used by neurotransmitters. Ok.
07:25 this is an a right here in circulation. It's some bad news going
07:38 . The virus can infect vascular athelia which further provide access to glial cells
07:44 C MS. Alternatively, it can the virus across leucocytes can transport the
07:51 across the blood brain barrier and facilitate infection of the C MS. In
07:57 when we talk about the blood So this is the entry of the
08:01 , right? But there are more with the blood vessels. In
08:05 COVID-19 is viewed as coagulopathy that the . Now in the peripheral nervous
08:13 the most common main symptoms are loss of smell and agua loss of
08:23 . We're focusing on C N So, C N S, what's
08:27 is imaging will show hypodense areas using T scans. So C T
08:32 if you recall it like a computer that uses x-ray, it's good for
08:37 up changes in tissue densities and uh growth of abnormal tissue also bones.
08:44 it is picking up some hypo hypodense . Hyperdense areas can be picked up
08:50 . In this case, it's hypodense of being picked up. The main
08:54 are a headache and vertigo made acute negro against the py and
09:06 So, brain bleeding, essentially blood bleeding, uh and treatments for central
09:14 system infections. There's a variety of treatments by different hospitals, different
09:19 different countries and it says no inclusive . It's not one thing that helps
09:26 but there are pretty standardized treatments. protocols for go in 19 infections in
09:32 brain. So yeah, we can at this or maybe, yeah,
09:42 can look at this. And uh one thing that we talk about,
09:46 called cytokine storms. So mechanism of of cytokine storm and SARS COV two
09:57 in SARS COV two syndrome binds these receptors expressed in endothelial cells and enters
10:03 bloodstream by endocytosis. The entrance of viral particle detected as a foreign body
10:10 to the activation of macro badges and . This consequently triggered the release of
10:18 from the cells and also from other of the ethel. The cytokines of
10:26 in particular are responsible for cytokine regulation cytokines. So if there's too much
10:33 the cytokines, now being released by cells, they will damage an athelia
10:42 and will make a leak. So why when we talk about cytokine release
10:49 microglial response, it's a, it's normal response to injury infection that microglia
10:57 activated that there is cytokine release. this is basically awakening the immune response
11:03 repair response in the brain. if you have this, what is
11:08 storm cytokine storm, it's too much these pro inflammatory molecules and then essentially
11:15 them to the lighting and make the brain barrier leaky. And that leads
11:21 more cytokines, more deregulation and potentially to hypoxia and stroke, rupture of
11:30 vessels. A stroke, hypoxia is of oxygenation because you are damaging the
11:38 brain barrier, it's being leaky. part of the blood and oxygen sort
11:41 leaking out, not specifically rather than through the specific architecture in this
11:48 vascular architecture of the brain. So it's interesting in my other
11:57 I actually had a better diagram to for the, for the entry into
12:02 brain. And so I'm gonna use diagram and then, so I'm gonna
12:09 to this presentation. I'm actually gonna this to you because I cannot find
12:15 article that I was telling you about uh uh imaging flare imaging that we're
12:21 about. So I'm gonna use this . But let's talk about once.
12:27 you have a virus that climbs up into nasal epithelium, there is certain
12:34 architecture of the nasal epithelium that contains cells, microvillus cells, progenitor cells
12:41 the fact receptor neurons. So for virus to infect the factor in the
12:47 , it has to infect the cells have a two uh receptor and that
12:55 two receptor is not present in the factor receptor neurons, but rather it
12:59 present in these green susa cells. you can see that these sustentaculum cells
13:05 in the mucosal layer here. And migos layer is where you will have
13:11 odorous when you inhale in the nasal helium activating the cell factor receptor neurons
13:17 well as the virus. So the that virus infects it infects the tentacular
13:24 and then through trans cellular migration and the ol factor receptor neurons. And
13:29 Olfa receptor neurons, it migrates like . It migrates and crosses into the
13:39 water neurons in the olfactory ball. so annoy or loss of smell comes
13:47 basically losing some of these silly and some of these olfactory receptor neurons and
13:51 do have the ability to regenerate. nerve endings there will factor that you
13:57 the ability to regenerate. Some people with COVID-19 will lose this sense of
14:03 for two days, others for two . And there are reports of people
14:08 it losing it for months, sometimes years, even to have a student
14:13 said their brother lost so small for years. Why is that? So
14:18 the viral load. It's how effective immune response. That is right.
14:24 can have a really good effective immune or not. Such a good effective
14:28 response also circumstances diet, what vitamins consuming and and and things of that
14:40 . So, once it crosses the brain barrier, now it has an
14:44 field to play. Um and there three theories by which it crosses the
14:49 brain barrier. First of all, , it affects trans cellular cellular migration
14:54 the dial cells and then in endothelial cells infects glia and then infects
15:04 paracellular migration. In this case, type junctions have been compromised and they're
15:13 . So hypoxic potential if the virus crosses in through these loose tide junctions
15:20 asides and then infects neurons. Trojan hypothesis, which is which is carrying
15:29 virus will get inside and unleash the onto the C N S we uh
15:35 neurons. So horse remember the story the horse where big wooden horse was
15:41 to the city and they allowed for to come in and they thought it
15:46 a fantastic gift. And inside that trojan horse, it was an army
15:52 the city. So this is like good guy microphage and they let him
15:56 . He destroys the city. Neuro here by allowing for the virus to
16:02 infecting the brain tissue. So you three basically predominant mechanisms. One is
16:16 system activation and endothelial damage through the storm. So we talked about the
16:22 storm overproduction of cytokines will damage this lining like the blood brain barrier leaky
16:31 will cause uh abnormal inflammatory responses. second mechanism of action and a lot
16:38 people are viewing COVID-19 diseases is coagulopathy activation of pro coagulation factors and formation
16:52 the thrombus in the blood vessels. happens if you have thrombus formation of
17:00 blood vessel, the blood cannot There might be a pressure build up
17:06 . The blood vessel walls may stretch they burst and then end up having
17:13 a stroke um or swelling edema that talk about in a second. So
17:23 is the binding to H two So once it's inside the C N
17:27 , then you have infection of neurons glia and endothelial cells causing eventually through
17:35 immune system activation, necrosis and neuronal cell net. So, neuro
17:47 . Ok. So, on the nervous system side, the most common
17:54 is an S A A is a of taste. Here as we're talking
18:00 CD scans, we're coming back to same slide, headache and vertigo main
18:05 , major symptoms, stroke, A N E and hemorrhaging. So
18:12 is another a little bit of a . But another way to view these
18:16 in the periphery, you have virus mucosa inflammatory response and loss of smell
18:24 of taste. The virus gets into brain and the secondary olfactory bulb
18:30 It can essentially start infecting other neurons glia and the brain leading essentially to
18:37 and cerebral edema, which is the of the brain viral entry into the
18:44 viremia leads the virus to cerebral A two receptors. The same
18:50 breakage of blood brain barrier causing cerebral . Cerebral edema compresses the brain stem
18:56 alters respiration. So not the infection cerebral edema is altering respiration because edema
19:04 swollen and brain stem has nuclei and responsible for heart rate and breathing.
19:13 the brain swells, it has nowhere go. You know, skull cat
19:17 expand twice its size. Neither can neck that means the pressure and ran
19:23 and the meningeal pressure builds up and builds up so much that it actually
19:29 physically pushing on the nuclei in the system that are responsible for controlling breathing
19:36 causing respiration changes and respiration. It's upsetting neuronal function because of the
19:44 not because of the infection or cell , adverse immune response can lead to
19:50 infection. Cytokine storms that we've talked that leads potentially to Nero of Phil
19:58 hemorrhaging respiratory stress because they have loss oxygen in the lungs besides neurons which
20:07 very sensitive to loss of oxygen. , if neurons do not get oxygen
20:11 two minutes, they start dying. other organs, if they don't get
20:15 for a long period of time, they're deprived of oxygen, they also
20:20 an organ failure and other organs failing also lead to additional neuronal injury in
20:28 brain eventually leading to hemorrhaging encephalopathy or swallowing and neuronal cell death.
20:45 consequences are here again. About one of patients that get hospitalized will have
20:51 complications since the fall of encephalitis. very common scheming stroke, post infectious
21:00 complications could be different wants and intensive related neurological manifestations also can be different
21:10 . Uh but being in intensive care a, is a tremendous burden,
21:15 and mental burden. And if you're the intensive care, that means you're
21:19 much being intubated. And that means one of those three or four people
21:26 will not come back alive. So outcomes are are significant. And if
21:32 do come out of the IC you will remember for a very long
21:36 , all of the beeping noises, stress, the the emotional distress,
21:43 , and also the physical distress of of oxygen, organ failure, uh
21:49 brains fall. And for that I included this article here for you
22:00 your additional reading literature. It's because wanna tell you that COVID-19 will also
22:13 to cognitive impairment. So, besides stroke, besides the scheming stroke or
22:22 or thrombosis and rupture of blood vessels to thrombosis. This is uh also
22:29 good good diagram that summarizes everything. COVID, you have cytokines,
22:37 microglial reactivity go up, you have , neuronal glial disc, look what's
22:44 . Oligodendrocyte goes down. That means axons are going down because in C
22:50 S oligodendrocytes uh cause insulation, hippocampal goes down. Astrocyte reactivity, reactive
23:02 . Remember, and that's the process metabotropic glutamate receptor. Too much
23:07 too much glutamate release. So now talking about glutamate and calcium toxicity also
23:11 follows neural circuit disregulation and cognitive impairment the form of brain fog. And
23:23 brain fog. If you think about is brain fog, it's not just
23:28 you didn't have enough coffee. Somebody brain fog that is cognitively not as
23:35 . It's because of these underlying come call and structural changes that are happening
23:43 to COVID-19 infection. So, keep mind that it's not only uh especially
23:51 the long COVID neurobiology, it's not inflammation and cell death demyelination, all
24:00 these decreases, synaptic pruning goes up altered synaptic function and astrocyte reactivity,
24:08 of these processes they're happening in your . Therefore, they're gonna contribute to
24:14 mechanisms of cognition and brain fog is described that way. Um It's just
24:23 cognitive impairment and ability to remember a of things in a, in a
24:28 manner. I'm attaching a couple more for you. Now, finally,
24:33 was trying to, to find this lost uh image here right here because
24:48 talked about epilepsy and seizures. And talked about how in epilepsy, you
24:56 have epilepsies and seizures has come about of the infections. So this is
25:04 way phalli infections can cause seizures. in this article, this is really
25:13 , it's incidence of epilepsy and seizures the first six months after COVID-19
25:20 It's a retrospective cohort study, but really impressive. They analyzed 860,000 electronic
25:31 records and they compared the incidence of in the first six months of those
25:40 had COVID-19 infection versus those that had flu or the influenza infections. And
25:52 they found is that hazard ratio, and hazard ratio of epilepsy and people
26:03 had COVID-19 infections was greater. Was greater than it was in those
26:14 had infections with influenza. So this outcome probability, this is basically the
26:23 of being diagnosed with seizures or epilepsy the first six months following in blue
26:32 influenza flu infections versus COVID-19 infections. you can see that there's a
26:42 much higher probability, almost 50% more probability to develop seizures and epilepsy following
26:52 infections versus your influenza flu infections. when people look at this virus lightly
27:01 discard, it is just like you're gonna get over it. There's
27:04 lot of things we don't know There are these dormant hypotheses that are
27:12 starting to circulate. Can the virus dormant just like herpes zoster virus does
27:19 shingles follow the chickenpox infection. There's virus in its state dormant someplace and
27:29 not really picking up through nasal you're not testing positive, but then
27:34 lose a sense of smell or something happens. And that's because that virus
27:42 or as it's sitting dorm at the low levels, it's not being
27:46 but it's actually causing some long term haul effects. COVID infection effects like
27:53 some patients. So there is definitely increasing uh knowledge base and trying to
28:02 the relationship between epilepsy and COVID-19. this seems to be at least in
28:08 to the flu infections, much higher . A seizure sy lys with
28:14 So it's more dangerous to the It's more dangerous to neuronal circus that
28:18 it can alter neuronal transmission of neuronal in a way in a much worse
28:25 than do the common flu viruses. , that's so as I mentioned,
28:35 can also look at this diagram. I may I ask you questions here
28:42 what we already talked about cyto gun and the invasion of COVID-19 virus factory
28:54 invasion of COVID-19 virus aside uh infection of microglial cytokine storms and then on
29:04 subcellular level, an MD A receptor amber receptor involvement too much calcium,
29:11 much glutamate leading to calcium cito toxicity glutamate exci. So I will not
29:18 you to label things in this But I will may ask you general
29:23 whether an MD A receptors are involved these processes or glutamate toity. Uh
29:30 then I have this really interesting but I'm not gonna discuss it because
29:36 just cannot find the article and I like doing that because I'd like to
29:40 you the reference point. And uh only thing that I will mention that
29:46 was gonna talk to you about is very interesting magnetic resonance imaging technique called
29:51 attenuated inversion recovery or flare technique that's emergent and uh can be combined in
30:00 case to record E E G S image brain activity. And this is
30:06 case where there was an increased seizure in a patient that had COVID-19
30:15 But I'm not gonna get into more . All right. And this actually
30:22 our last lecture of COVID-19. I in the subject matter and I have
30:30 brain injuries. I think that one view COVID-19 almost like a traumatic brain
30:37 . Because think about when we talked controlled cortical impact where you have damage
30:45 you have the fluid repercussion model where causing swelling, causing abnormal uh activity
30:52 neurons, but also in the blood . Um and I think COVID-19 infections
31:01 still a very important subject matter for to know. So if you can
31:06 some of these mechanisms by which virus enter into the brain, some of
31:11 major mech mechanisms to cytokine cell apoptosis or um called opathy, thrombosis
31:24 blood vessels, potentially leading to And what I did is I kind
31:30 combined two presentations into one. And I will do is I will combine
31:38 for you. So you don't have have to and replace the existing one
31:43 you to prepare for the exam. additional papers are there. So if
31:47 want to review some of these mechanisms we talked about or greater detail,
31:54 think in one of the articles that about the peripheral and and central effects
32:02 COVID-19 infection, you will find it the in the folder here. This
32:07 the one that I OK. So in your lecture folder. Um under
32:17 content. If you go to your folder and we'll show it to
32:22 lecture, reading, supporting materials and uh haven't activated yet. So we
32:32 be there in a second. But , this concludes our in life
32:38 We will have one more meeting for term three or exam three review on
32:45 . That will be over soon. we'll see everyone will resume on Wednesday
32:53 those that came into class especially you . Thank you very, very
32:59 I think Johnny was another one that constantly here most of the time.
33:05 appreciate that. Uh, and wishing you to have a good rest
33:11 the semester and good luck on the
-
+