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00:02 This is cellular neuroscience. Election And what we discussed last lecture where

00:10 medications that are available that our pharmaceutical cellphone nine THC synthetic one made a

00:18 nine THC. And CBD cannabidiol CBD specific conditions specific symptoms in specific

00:29 Then we talked about how there is lot much more evidence that Canada's and

00:35 can help with other conditions that are listed on the specific pharmaceutical cannabinoid list

00:44 that there is this uh decision was by a group of very talented

00:51 Now it would be about five years . Since then there is even more

00:57 information that's emerging on their therapeutic potential capabilities of. Mhm. We talked

01:05 how in cannabis plants naturally you have production of Delta Mind THC because there

01:14 a Delta mind th C. That gets produced in the plant.

01:20 it's a civic version of DELTA nine A. That gets produced in the

01:25 and this is the neutral version of of latitude and this is Finding two

01:33 1 receptors and interacting With the receptors the brain. And we talked about

01:39 the we TV one receptors will control neural transmission and CB two receptors which

01:45 not shown in Lisbon infographic are controlling of the slower processes such as inflammatory

01:54 immune responses and mostly mediated by glial . We talked about cannabidiol CBD as

02:02 of the major cannabinoids together without the THC also C. E.

02:07 A specific version of it. And we discuss that there is delta eight

02:16 or delta eight THC. It's typically from CBD in a semi synthetic

02:23 So it is not made by the . And it has sort of a

02:29 falls within the medium range of binding to CB one receptor than ACB one

02:37 is responsible in the brain for causing intoxicating or the highest facts. Then

02:46 88 c. It's very likely essentially A certain high level of intoxication as

02:58 . What we don't know about Delta actually was not well studied and anecdotally

03:05 users don't process that plane as fast the process of natural daughter of

03:11 The other warning on the market that where the anatomy of the solvent including

03:18 is that there is no standard way producing. If there is a standard

03:23 we know that cannabis plant contains the THC a cannot be the C.

03:29 . D. A. We there multiple ways by which there is a

03:36 of this double bomb shifting of this bond from 9 10 to minus

03:44 And it's a har chemical prices and are not certain about the contaminants and

03:53 that might be left over. So is a great debate right now.

03:59 ongoing in the state and probably will be on a better level how How

04:08 Delta eight, there's also another version Delta 10 THC. That would have

04:14 double bond between 10 of carbon town here. So we don't know the

04:22 term of facts and we do not much information on the position of the

04:26 And in this situation here when we about the music effects of cannabis and

04:31 we're typically talking about THC and THC CBD and when we say THC capsules

04:39 least in this text here it is nine THC. Not that the versions

04:46 it. Canada's plans. As I , it comes in many different unique

04:54 just like when you go to the store for example, you can pick

04:59 the variety of the apples, granny apples and some golden crisp apples and

05:09 banana, crisp yellow apples whatever all the different apple trees, apple strains

05:19 we have. And so those we all know they look like apples

05:24 they are different, they taste they smell even different. But we

05:29 know that apple. These are different of apples. Just the same way

05:35 are different varieties of cannabis and what different about different varieties of cannabis is

05:41 expression levels and combinations of servant phenomenal terrapins that are produced in the tri

05:51 and terrapins. And these aromatic molecules cannabis is known for expressing a fairly

06:01 variety, dozens of different Karpin's and of these carbines are quite dominant in

06:10 sense that there will be significant concentrations one to several percentages in total mass

06:19 Canada's plant of these turkey wings Such Lemon 18 and then a curious feeling

06:27 carrier fill in is actually a selective two receptor agonist. So some of

06:36 therapy ins like carry a felon are can have been mathematics. They imitated

06:44 mimic activity of cannabinoids by binding to receptors to carry a filling in particular

06:52 can be found in clothes and hops binds to CB two receptors, it's

06:59 selected CB two receptor agonist. And why not? And so these terrapins

07:08 in different fruits and vegetables and herbs plants and they're also expressed by cannabis

07:18 . And if cannabis plants are dominated CBD for example and Lyman ian it

07:25 have a certain the fact that it be a certain strain genetically that produces

07:33 and it's typically produces this lemon flavor the CBD dominant strain. And if

07:40 strain for example is dominated by THC by Lionel. So then that cannabis

07:50 will have a different effect because THC CBD will interact differently with CB one

07:56 . So the psychotropic effect is going be different from these Canavan ons.

08:02 also the accompanying effect. These therapy can influence how that THC is processed

08:10 with lina low and how winnable would give Canada strains that are dominated by

08:18 . You see for example the lavender smell. So now you have different

08:24 of cannabinoids and Turpin's and uh while made this funny image uh this is

08:34 you walk through a Canada's garden and a hemp garden and hemp gardens,

08:40 an hour outside the Houston here federal . You will smell in some parts

08:46 that garden like lemon and some parts that garden will smell like skunk animal

08:53 , lavender and other parts will smell gasoline and blueberry. And quite often

09:00 Canada strength when they named they could incorporate or do incorporate the dominant

09:09 So there's blueberry this and blueberry that of the cannabis strength, there's also

09:15 strengths that are called skunk because of particular uh now that reminds people of

09:23 skunk smell when you drive on the . Um and you smell skunk or

09:29 walk through the woods and and you smile itself. Now these turbines,

09:35 have their own physiological and therapeutic They're being studied and they have been

09:43 , I'm not saying that they're accepted pharmaceutical medication. I'm saying that there's

09:49 lot of indications and evidence that these et Merci finding and line a little

09:57 are some of the most dominant therapy that you will find um including better

10:03 film but they have their own properties what's interesting for example, is lying

10:13 the end has anti carcinogenic and Elliptic immuno stimulation properties in humans Morrison

10:22 anti inflammatory analgesic realistic, which is relieves anxiety. Now interestingly out of

10:29 is a cyclical industries you give So when we talk about all these

10:34 disease, I'm going to talk about common education and the common medications for

10:39 disease are colonists, terry's inhibitors and alba pining which is present in

10:46 Also counteract memory deficits that can be by THC. So all of these

10:53 Turpin's, you will not have to exactly what they do. But it

10:57 be important for example if you remember better carry opulent as a cannibal magnetic

11:04 in that seem to be too selective . That would be important to know

11:08 the test. It would be important milk with a task that uh different

11:14 of cannabinoids and Turpin's determined what what call the final output chemical outfit of

11:21 plant. And it depends on the , it depends on the growth

11:26 In the end, if you have , it's genetics for a certain strain

11:31 will express or supposed to express a phenomenon such as CBD and certain turkeys

11:38 environment. So that's important to It's I think important to remember this

11:45 Alba p. 19 is a silver colonoscopies inhibitor because that will come up

11:50 the following election. So now we different medical programs. We have national

11:56 international programs that these are pharmaceutical programs of duty calls all health insurance

12:03 We have national cannabis and international cannabis have in Germany and pharmacies that's marijuana

12:10 is solved in Germany pharmacies and it's from other countries. Also, health

12:15 is up to Saddam has to have regulated cannabis in the United States.

12:20 example in Massachusetts with many states Louisiana is another example in the states.

12:26 they have both medical and recreational programs medical patients will be getting a tax

12:32 of 20 that they don't have to but adult users they have to

12:37 Also, the distinguishing features is for , an adult use of recreational

12:44 It's also state regulated in the United . But also there are countries that

12:50 international levels such as Canada. But specifics of that free available cannabis.

12:58 is province specific and provinces have their rules for selling tobacco for somebody

13:04 And in this case in Canada for Canada's as well. Canada and

13:11 So for adults uses is typically full that's particularly controlled at the local level

13:18 can even be controlled by a city be controlled by quality. Uh and

13:24 far as what can be sold or facilities can be operated is very much

13:29 very complicated web out there. This the current state. This is December

13:35 . So it's not really current You can see dark, you have

13:40 and medical use regulated program everywhere you light like in texas, you have

13:45 and low TSC program. So we'll what you have in texas with a

13:49 we have green, you have comprehensive cannabis program. So you can see

13:55 I would say maybe half of the if you take Northeast New Jersey,

14:01 want adult actually. So New Jersey not dark, dark green too.

14:07 , and I think pennsylvania and Ohio to be soon anyways, if you

14:12 the Northeast michigan Illinois, this is recreationally or about these cannabis. And

14:19 in the west coast California, the states and but about half of the

14:26 , maybe not quite 45% of the has adult in medical use programs.

14:34 then you can see that there are states like Idaho, Nebraska and

14:41 which is also changing maybe even South that they don't allow any access to

14:49 at all. So what's happening is is no federal program for medical

14:54 The only federal program exists for So there are all of these different

15:01 and then all of these different state , you have different products. So

15:06 when you talk about them, they have a word system that you learned

15:10 . It's a vast system. Let's out the distributed throughout the body.

15:15 you inhale something which is smoking of authorization. The effect is immediate because

15:22 of cannabinoids or turkey means and so the lungs very quickly distributes hysterical into

15:27 blood. Now everything that is ingestible . Oral ingestion. So just sublingual

15:34 and swallowing oils and gummies that actually about it, you swallow half of

15:40 it goes into the digestive system, exposed to very low ph gastric

15:46 parts of the broken balance start getting and enters into the digestive system where

15:52 starts being observed, observed. And this oral ingestion rod can be a

15:59 effect. The onset of the fact you're talking about psychotropic onset for medicinal

16:06 concert from cannabis plants and turbines can half an hour. And some instances

16:12 the person has flown metabolize, we take you up to two hours for

16:16 effect to start showing also the fact something injustices prolonged and when something is

16:23 , it gets through the secondary And one of these is oxidized in

16:30 liver to produce delta nine THC seem . That produces 11 0.

16:37 THC. And that is also psychotropic intoxicating molecule. So some of them

16:43 , some of the economic metabolized and the have a psychotropic, the fact

16:48 the adjustable products or very status laws christmas cookies, you never know what

16:53 states we're going to find when you about ratio ratio to see 1 to

17:02 . What does that mean? That that there is 10 mg of THC

17:06 10 mg of CBD in the service too long means that there is if

17:10 THC dominant for times of the THC if there's one time of the THC

17:16 for serving or totaling a product. that's very important that we consumers to

17:21 because THC has negative side attacks. And CBD can can reduce some of

17:30 negative side effects. And for THC can evoke is not recommended and

17:38 make problems worse with people that have , psychosis, schizophrenia or have those

17:47 of mental psychiatric disorders. Maybe the in most cases by health care practitioners

17:56 be to focus on CBD rather than of course they have top of those

18:02 , sounds chopsticks patches, depends what you're in or development in the state

18:08 texas. These are the two product that are allowed adjustable products and topical

18:15 flour, which is cannabis flower, buzz basically it's both the product and

18:22 commodity because you can have a final that you're selling out of this

18:27 not in the state of texas. you can have a commodity which these

18:31 and gummies and oils that come from . And so it's a commodity that

18:37 being sold for somebody else to make product. And I'm telling you a

18:41 bit now that the market, which interesting and some of the opportunities that

18:44 may actually be a part of in future, that's what your interests

18:51 So THC CBD cannot influence up to and the plants that can be produced

18:59 one g of high THC cannabis without . Pre rolled joint with, let's

19:05 20% of these, he contains 200 of THC. So Typace one joint

19:15 being shared dependent on the concentration we're on the person's tolerance of medicinal

19:25 But 200 mg it sounds like a . But if you ingest it,

19:30 it and immediately it also gets metabolized processed faster than the adjustable. Um

19:39 not the case with the adjustable and not the case with the doses for

19:43 . So in most cases doses for would be when you talk about delta

19:48 THC is about 10 to 20 And the fact like I said,

19:54 delayed, it's longer and it could stronger and that's the reason for it

19:58 it goes through the justice system of tabloids. And then when you talk

20:03 concentrates that are available in different concentrates. Traditionally we discussed how William

20:13 used hashish and Rosalind resin essentially, was either pressed or it was alcohol

20:20 . And then there are different variations these products on the market shattered battered

20:26 when new variations coming up And they're concentrating too. seems CBD or other

20:35 from natural Kwan's up to 90 and many instances there is an argument.

20:45 why do you need such strong ah of THC and if you have such

20:54 concentration, that's true. But most the people that are problems with Canada's

20:59 for with adjustable and would concentrate. because they don't understand that the difference

21:07 Canada's flour is 20 and cannabinoids and concentrate up to 90 and the way

21:16 body processes, it adjusted the way interacts with every step tourists, it's

21:22 at the same time. If you about medicinal delivery of something that you

21:28 to have concentrates because you want to as much as possible with as little

21:35 as possible when people inhale plant which is flour, There is remnants

21:43 everything else and the leaves that are and it's actually heated temperature. And

21:50 there's a lot of plant matter that not gonna happen. Cannabinoids are only

21:56 and then concentrates the plant matter essentially it's being removed. So for medicinal

22:03 , therapeutic purposes concentrates are going to gained popularity as well as they're going

22:09 be properly. Micro does the micro , so people use them responsibly to

22:16 the medicinal effect without getting themselves into panic attack in the emergency room.

22:24 , what's interesting about Canada's market in United States is that in general and

22:30 talk actually gonna give these talks, business colleges and a master's programs at

22:38 Business University. So you want to about the entrepreneurship and business aspect.

22:44 interesting in cannabis is that there are that are basically plant touching companies,

22:53 plant touching companies, if they're they're operating under the federal law and

22:58 they still need to abide by state because if there in South Dakota it's

23:05 no go even with them. But they're in marijuana, they have to

23:12 to the state regulators and follow all the regulations very closely and rules and

23:19 there is a mistake on this the fines are millions and millions of

23:26 in funds. So it's very very regulation and security around the marijuana high

23:33 cannabis plant touching businesses, manufacturing, , manufacturing, producing the products.

23:42 there is non plant structuring businesses and anything, it helps the plants grow

23:49 helps the extraction. So non plant businesses and cannabis can be microscopes that

23:57 at the tri cones and predict something tri cones that their online technologies and

24:07 , they are delivery services. They're plant touching a little bit but they're

24:13 not touching the product, they're just it. There's a lot of medical

24:20 around medical patients. Uh there's a of research is going on. Um

24:27 is a lot of white extraction solvents, fertilizers, cleaners, everything

24:41 related to basically this massive agricultural One of the interesting things that's popping

24:49 of these companies which is uh, jame or dutchy or what is this

24:56 for. And if you don't know website it is, maybe we'd laps

25:02 . Yeah, these are tech companies companies, Non planning budgeting companies.

25:09 has become accompanied and I believe $4 dollars valuation within two years because they

25:17 a technological solution for the consumers and businesses. Some of these companies analyze

25:24 lot of data and they know how use the data in order to drive

25:31 sales. It's a whole complete subset he technology, the whole complete subset

25:38 marshaling online marketing, social media, , influence of marketing. It's a

25:45 world of cannabis. Um There is standard, there's no standards products,

25:53 no standard of labels. You can from colorado to California and you will

26:00 find the same product. You will know if you find the same

26:04 you don't know what is labeled. th CSR just delta nine THC.

26:11 your C. D. G. ? And you test for C.

26:15 . I don't know I just do spectrum, full spectrum refers when there

26:20 an extraction or concentrate made, contains full spectrum of all of the

26:27 Where's my CBD products? That's that's that's online with the CBD shop or

26:32 the gas station? Where do you by your medicine? Who's advised?

26:40 you gonna trust? What labels are going to understand? What brands are

26:48 going to be able to find the location? I want to talk about

26:53 and I'm talking about CBD other strange believing and if you can find it

26:59 across the States and can you find international. So the community is setting

27:05 standards on these products are very much in finding the solutions to these problems

27:10 myself. The technological level. what we have in the state of

27:15 is 1% THC level, which is mg THC program, Home Farm

27:21 which is helped 0.3% THC three mg THC program in a finished appliance

27:30 And also in the tropical products. a lot of edible products of three

27:36 per gram of THC. And you do the math. If you have

27:40 five grand products, you can have 15 mg THC does intend to hand

27:44 Bill and that was not intended by regulators. So this problem, 0.3%

27:50 nine THC. And now the problem Delta and Delta 10 th these are

27:56 to have to be sold and in , there's a bill that hasn't been

28:02 yet, institutional review board, which that there is going to be allowed

28:07 and medical schools and hospitals on the cannabis products that are sold in texas

28:14 if once that goes through, once is an alignment of the medical schools

28:19 hospitals and some sort of a federal that says, okay, we won't

28:23 everybody in medical schools and hospitals doing with dummies because only 20,000 people in

28:30 Vietnam. Uh, then at that in texas could become a leader and

28:36 cannabis research, But right now the is in 1% Texas has legislature every

28:43 years and so 2021 is one of last Round of Laws was acceptance of

28:51 . It's going to be a new of the laws in texas. It

28:56 not called the medical cannabis program. is called texas compassionate use program.

29:01 traditionally, not surprisingly because it's a long history recorded history. The first

29:08 and the first program that opened in allowed only intractable seizure disorders. Intractable

29:18 to be treated with these very low THC preparations and in 2017 that concentration

29:25 even lower. Now these conditions, you can see the list protects us

29:30 fashion abuse program is all neurological conditions cans but most of them are

29:39 Parkinson's peripheral neuropathy. Of course it's the periphery dementia, Annapolis. This

29:45 . S. Uh seizure of art is um cT And plus over

29:56 incurable neurodegenerative disorder. So in the of Texas is the Texas state of

30:03 . We have a partner of public texas DPS which are, you will

30:09 them on the highway as texas, troopers but they do a lot of

30:14 in the states like they teach people to paddle their kayaks and they also

30:20 Canada this program that's what we have texas now you've learned enough and I'm

30:28 to pause the supporting for the second to the next section. So now

30:35 we learned about epilepsy and medicinal historical uses of cannabis and cannabinoids.

30:42 even the historical use of medical Canada's in texas for treatment of epilepsy.

30:51 you started Migraines are don't believe on list that I just showed you.

30:58 on that other 100 uh neurological disorder so Migraines is probably the correct way

31:09 saying it because typically people have more one and they repeat. It's a

31:18 debilitating brain disorder characterized by recurring attacks moderate to severe headache is often a

31:24 by other neurological symptoms. They can enhanced sensitivity to sensory stimulation such as

31:34 , sound touch or all factories. there are different subtypes of migrating with

31:41 but also distinct critical features. A of the people that experience migraine experience

31:51 aura and so we talked about aura precedes seizures and there is an aura

31:57 precedes migraines and what that means is the severe headache is preempted by some

32:09 of sensory disturbances or motor disturbance and commonly a person that has migraine.

32:21 now we can speak from personal I suffer from migraines and my migraine

32:30 us are visual and what happens is start seeing little floaters, meaning that

32:40 cannot keep focused like see blurry parts the visual field in several areas and

32:49 typically starts in the same part of visual field, which indicates that it's

32:55 typically originating in the same circuit someplace communicating that information to divisional circuit and

33:05 that typically minutes there is an answer of pain and that pain can be

33:18 for other people. It's tactile sensations much sensitivity. They become too sensitive

33:25 touch. That's the hora. There be motor speeds, disturbance is actually

33:32 first migraine and the most severe migrants I have. I cannot properly

33:40 So I start either speaking in cyclically repeating the same thing or I

33:48 to stop speaking and very selectively select word and say followed by another word

33:56 saying otherwise. They kind of communicating items. So in the 19 forties

34:04 three hour dr milner proposed that the unified migraine aura may be secondary to

34:12 propagating quarter for formalin on that's called spreading depression before depression. Clinical depression

34:18 real. The slowest fraud and cortical of neuronal and glial decolonization followed by

34:26 of the community. You guys are smart to understand everything I understand.

34:33 this is the schematic schematic representation of cortex and in relation to this trigeminal

34:46 pain talk would which reminds me I have a uh huh. It's slightly

34:56 presentation here that I wanted to insert few spies and activation during migraines the

35:10 and neurons they don't have pain receptors so the pain is explained through this

35:20 complex and try to grab them at vascular pathway and we'll look at this

35:26 when we talk about the war on we talked about cortical spreading depression,

35:32 talking about this cortical spreading depression that's from as was described away from the

35:39 organizations. And so the mechanism behind the cellular mechanism is that there is

35:47 rise at least. Professor Rist Edie's from brazil explain this by saying that

36:02 is an accumulation of the castle just selling the potassium and low ph in

36:09 extra salary would space. Okay. reach peel arachnoid on durable surfaces and

36:18 the dairy in vascular sensory appearance of trigeminal ganglion teaching neurons, signals are

36:27 . Men in general know susceptible know of pain receptors are related to the

36:35 nerve processing. So trigeminal nervous and nerves that will process it's a sensory

36:45 motor nerves but sensory it will process a receptors of the pain from the

36:53 but also know susceptible which are pain . The dye germinal cervical complex which

37:02 TCC it's situated in the medial aspect cerebral cortex. Okay sorry. In

37:11 brain style. And then from TCC goes into the thalamus and from thalamus

37:21 you know it goes into cc which the singular cortex also referred to singular

37:29 salt off of the Singulair vortex and in emotional and effective processing the season

37:39 ptolemy's in several regions of the frontal the temple for attacks. Yeah.

37:48 this is sort of that wave of . The surprises in fantastic with the

37:54 in ph activates neurons, neurons deep . If you increase expressivity of potassium

38:03 , remembering potential of neurons is going go up it's going to be

38:08 it's going to start firing action for shells, there's going to be a

38:13 sink for me. And this wave cortical spreading depression is a slow wave

38:21 so it is thought and typically that have for example visual disturbances the primary

38:28 cortex and the visual cortex in general located in that exhibit a world.

38:35 these cortical spreading depression wave fronts can in the exhibit a love that can

38:41 from the border of occipital parietal. could originate in that motor areas or

38:48 standing in motor areas rather than traveling them and therefore the fact is going

38:54 be more on the border areas. Professor is the one that described this

39:02 and I actually followed up on some his work experimentally and my students also

39:09 studying cortical spreading depression and it is phenomenon that cellular mechanism about phenomenon,

39:17 expression of that phenomenon. It is similar to the mechanisms that you see

39:24 seizures and epilepsy but there are also . So the headache phase activation of

39:31 trigeminal vascular system that conveys those accepted from the men energies. Central brain

39:39 of cortex you may have a transient in Egypt, you know what global

39:46 is. We there there are different of the media expressive receptive global

39:53 This is a transient global amnesia. each may temporarily forget everything. You

40:00 temporarily not be able to recognize the , forget your phone number, forget

40:05 to dial 911. So this is cortex it is not clear if it

40:14 but it modulates and amplify sensor Two if the hypothesis is that there

40:21 some sort of a hypersensitivity sensory inputs and mind you pardon? The migrants

40:28 often are also a consequence of stress . And it could be also a

40:36 of other things. So it is clear. But if it's a sensory

40:42 in other words, if there is parliament, there's hypersensitivity, the visual

40:54 or to the auditory impact. Then those could be the sides war.

41:03 could go through the salon of circuit uh singular cortex other circuits in my

41:11 path of physiology. So I'm a type of environment, brainstem, trigeminal

41:20 , all of the stops here. llama cortical okay hypothalamus. The hypothalamus

41:26 be involved brainstem because of the trigeminal here, trigeminal ganglion this is the

41:35 is that they're typically there's no self even following severe and prolonged migrants but

41:46 of neuro degeneration. What you have you have this massive, massive metabolic

41:53 on the brain. So the brain consumes 20% of your total body

42:00 Now as you're experiencing these particles starting waves and the pain and the

42:07 it's a huge metabolic drain of neurons it's also a huge physical drains a

42:13 of times when people undergo an attack migraine attack and they come out of

42:20 whether they're at home with the medication doing something or getting called from the

42:26 room, they typically feel that their have been beaten up with with the

42:35 bat and quite off of their bodies well. So there is this depression

42:41 that follows cortical spreading depression and this waves to speak in the pain.

42:48 lessons to the responsive Itty in the . Look at the cellular, we're

42:55 in business for this. Here is description. Trying to explain to you

43:02 trigeminal nerve vascular activation disease. These cascade of signaling events is depicted on

43:08 cortical surface following cortical spreading depression and transient opening of the national panics and

43:17 and this connections and foreign accents. junctions. So gap junctions and the

43:25 of these slaves. A lot of is implicated to the gap junctions.

43:32 . So side of teens across the that are released from real cells across

43:36 real limit mints to reach sensory axons discharge appeal and dural try general axons

43:43 are carried centrally to the trigeminal ganglion trigeminal nucleus for Dallas T.

43:49 C. CS. Ds do induced inflammatory response and mast cell degranulation within

43:58 inches plus reflex violation of physical Rbb of great satisfaction. So this

44:05 this metabolic burden causes a certain this of the pro inflammatory molecules. And

44:13 could potentially be that we're not sure this is actually the chicken or the

44:19 . Maybe there is over in just of some of these uh frosted wind

44:24 some side of kinds that that we're about. Um But you can see

44:30 neuronal real processes with this leo cortical depression. Wave split wheel wave migration

44:40 basically releases the floral inflammatory molecules um group protein one B one. And

44:50 we can one be one. Doesn't . I will not ask you the

44:53 but there's a pro inflammatory molecules. . And then you have the release

45:00 the side of kinds and the press noise and then you have basically accusations

45:07 the uh of the trigeminal ganglion and activation of moses receptors which now produces

45:16 perception of pain through the trigeminal But that is again community communicated back

45:25 the cortex. So this is actually conditions better there are larger. So

45:39 is the spreading depression the wavefront of and spreading depression. Then you have

45:47 massive deep polarization. This is extra recording here. Okay and this is

45:54 potassium concentration. K plus concentration. can see that there's a rise in

45:59 concentration. You can see that there a drop and sodium and chloride as

46:08 drop in calcium and there's a rise glutamate. And so these are all

46:15 the electro physiological and ironic features that the dendrite and Selma's recorded extra salary

46:25 to face these organizations. And if record and for cellular early you will

46:30 this from the resting membrane potential about 65 68 syllables have this massive

46:37 You see at the beginning of this polarization you have a few spikes that

46:41 produced But the rest of it is very prolonged you see this as 20

46:47 Timescale. Their prolonged in bed slow beds were reporting from one cell this

46:54 was going to move over this one in one minute it's very slowly

47:00 Gonna move to Mexico Mexico Mexico Mexico that's why it's very painful. So

47:11 you can have high potassium injections and producer of this particle spreading depression.

47:18 and one of the models to replicate models to replicate spreading depression is to

47:26 and increase the extra set of the concentration. You can also change as

47:34 sell the concentrations capacity sodium chloride. because because we just discussed so when

47:43 talked about seizures and we talked about and we talked about cellular mechanisms and

47:48 said oh look there's this synchrony and . G. And there's abnormal brain

47:56 . And then I said oh look these traces from neurons and these neural

48:01 them and these new inspire them. and word is kind of a was

48:08 and discussed on the electrophysiology and cerebral . When we talk about the period

48:16 the actual seizure activity which is referred as efecto activity and the activity that

48:24 between the procedure advance, which is indirect activity and what we looked

48:33 And we looked at seizures and We looked at the X. Selectivity

48:37 we looked at the interplay of excited the industry sells during the collectivity.

48:44 is a trace of a recording where have a wholesale reporting uh produced by

48:51 and an extra sound recordings And these repetitive seizures. This is a time

48:57 of 30 seconds. So there are 40 some seconds 45, maybe 60

49:03 in duration. You can see there's deep polarization, a lot of action

49:08 . This is a parameter all And this activity that you can see

49:13 the single south is also recorded extra . So we already talked about how

49:20 . G. Except activity through the and extra cellular electorate picks up activity

49:27 outside of neurons and it represents a of an average activity of that neuronal

49:34 . And you can see that these advance or it'll enhance our very much

49:40 in the extra several recordings. That that there is a significant synchronization of

49:44 number of parameters all cells producing these potentials and visualizations at the same time

49:52 between these equal advance, you have events and these interregional events are much

50:01 duration birth. So instead of 40 60 seconds in duration, these bursts

50:09 anywhere From 70 to 200 to few milliseconds in duration and just want a

50:16 action potentials. And often they may even be picked out by the exercise

50:23 recording traces because there might not be synchrony in the network to be reflected

50:32 exercise recordings. In other words, a few cells may be synchronized to

50:37 and Tariq traverse, but much much numbers of cells need to be synchronized

50:44 order to produce these efecto. She really about, this is for

50:51 it is before seizure. We looked this excitatory cells here in the

50:56 This is an inventory, sell, a neuron, this is the pre

51:02 phase and you can see that in predictable phase. This into neural was

51:07 , I think the peripheral cells were now during the battle phase. The

51:13 neurons went into this what we call polarization block. So this is different

51:18 cortical spreading depression. This is a polarization block. During seizures and then

51:24 have this interplay of gloom and his fails excited to ourselves. Fire.

51:31 when the seizures then is finished. after that you have a bursting activity

51:37 that bursting activity in this case persists inhibit their self but not an excitatory

51:43 and this is post victim first So basically immediately before seizure is predicted

51:51 after seizures. Post Picton during seizure perfecto and longer duration periods in

52:00 Such exchangers are incorrect and this is happening during seizure than some parameter

52:08 With these parameters themselves be polarized and a few action potentials. They sit

52:13 and be polarized for a very long . This is a one minute time

52:18 . So this is 1, 3, 45 minute duration of that

52:24 a single south and also in the salary recording and the extra cellular our

52:33 here and the way that these experimental spreading depressions were induced were with application

52:41 potassium chloride. So if you remember potassium levels go up and they

52:50 cortical spreading depression. These are the mechanisms of cortical spreading depression and to

53:02 the cortical sparkles group depression who reproduce experimentally, we can apply potassium chloride

53:11 will basically raise exercises the potassium concentration we produce these very slow moving events

53:20 you can see just produce a few for tom Charles son, there is

53:25 and co essence the rest of the . So this is the dynamics are

53:32 spreading depression are different. If you define very clearly predictable pixel plastic tile

53:39 rectal in seizures and cortical spreading You have this phase of globalization firing

53:47 it's very slow and there's really no little activity. Now this is important

53:56 in some instances these inter erectile bursts the bursts that are occurring between

54:05 This is extremely important for clinical purposes for clinical diagnosis purposes. As I

54:13 , the person that has epilepsy and seizures. Their brains will be

54:20 And one of the ways in which can definitively diagnose if the person is

54:24 seizures is to have an E. . Recording of that seizure. But

54:31 a person may spend hours or days that seizure may not happen. But

54:35 may happen in between the seizures is incorrigible bursting activity. And if you

54:43 up, they give them part of brain with the E. G.

54:47 above the electrode. And you're lucky you picked up a circuit synchrony enough

54:54 recognize the directional verse in the G. Signal. That may suggest

55:00 you that this person or certain brain in that person are hyper excitable.

55:07 doesn't say that having seizures. So you saw intellectual burst, it doesn't

55:12 that I saw seizure spread from the 1617-12 and so on. But I

55:19 intellectual burst. And that is also indication of potentially epileptic brain. You

55:27 see that with cortical spreading depression. you put them in june recording.

55:34 wouldn't see much except that wave of polarization that would be very slowly

55:43 So there are two dominant hypotheses on etiology development of csd band harder than

55:52 eliminate hypothesis as a key regulator. is being in the initial D polarizing

56:00 of the csD. The extra celery and aspirated concentrations increase activation of metallic

56:08 is following by csD initiation compromises blood barrier permeability. High permeability of blood

56:15 barrier serves as a major reason for glutamate accumulation during the following CS.

56:21 . And more glutamate can come in the blood. In addition activation of

56:25 M. D. A receptor leads further deep polarization of glutamate release which

56:30 to see as deep propagation the high brain barrier from the ability also exposes

56:36 brains of the world concentration of magnesium is also an NBA receptor blocker if

56:43 remember. So if you lower magnesium you make the brain more prone to

56:48 spreading depression, resolving in further cell deep organization and outward potassium current therefore

56:56 accumulation on the outside of the So it's essentially extra cellular glutamate.

57:06 initial p polarization and then glutamate drives leaky blood brain barrier to allow more

57:14 to activate more than the receptors to the propagating legal activity. And then

57:22 of this deep polarization and self aspiring professional leaking outward and how national concentration

57:30 the second one is graph fest and hypothesis professed and proposed the release of

57:35 amounts of potassium during their own firing most accumulation of potassium extra seven which

57:41 colonized experience causes glutamate release followed by direction of normal excitation extra salary that

57:49 . And Natasha can also be. used the adjacent area. Yes.

57:57 he's saying that maybe that spread and potassium concentration slowly. Maybe even through

58:03 glial network with cause the origination of deep polarizing ways. So glued innate

58:12 versus like Cecelia potassium festo. And think that the truth lies somewhere in

58:25 or all together with potassium Alexa cellular leaky blood brain barrier and an accumulation

58:35 the polarization producing these cortical spreading So cortical spreading depression leaving corona will

58:41 a civilization that's present velocity of at six millimeters. And then at the

58:47 . Well across the federal quarterbacks, violator, physiological cellular live and migrant

58:55 response bottles of cortical spreading depression, potassium floor and application with mermaids.

59:05 manipulation of N. A. Pump. Why is that important?

59:10 does an ak pump do it rebuilds member of potential following the decolonization quality

59:17 action, potential firing. So it works against the concentration radio. It

59:22 needs a teepee. Energy, huge demand during? Mm hmm.

59:30 And what if you shut down the which works with a T.

59:35 What if there is a lack of teepee because it's being used for something

59:39 . And the pump doesn't have enough to a TTP. You now are

59:46 for themselves to be more D polarized the spot came not working. It

59:51 a presentation ingredients so you can manipulate ak pump and reproduce the cortical spreading

59:58 , mechanisms in the brain, electrical for hypothermia. So just like with

60:06 brow seizures, you can use hypothermia these people have seizures, you can

60:11 the tissue in the presence of hypothermic and also induce particles from compression.

60:21 injury can cause cortical spreading depression, frequency electrical pulses to stimulation, electrical

60:31 . All experimental particle spreading an apartment by high exercise at a level of

60:36 and glutamate induced excited toxicity. Wait second if there is glutamate induced excited

60:45 but there is a neuro degeneration, there is a significant toxicity from eliminate

60:52 can actually read. It's about the of neurons at least immediate neural regeneration

60:58 the sentences. All right. So do we see when we look at

61:06 from that trick imaging or functional imaging the brain for the migrants. When

61:17 talk about more For metric imaging, talking about the morphology and the metrics

61:24 that morphology is the shrinkage is the of certain cortex and altered gray matter

61:33 in the fizz Odjick migrant minors versus . So the study the study control

61:41 people that were having migraines, the that were not and they saw that

61:48 a cortical thickness and s warm. other sensory cortex has increased also an

61:56 all middle frontal for the migrant These are uh that bizarre rick

62:05 So but if you look at the versus the exotic migrant knows there are

62:11 differences chronic, the gray matter volume down. So there's a decrease in

62:19 late cortex and singular gyrus to talk frontal, temporal and occipital areas.

62:25 , mostly the motor auditory and visual , but there is a grave matter

62:35 increase and some matter something and the emotional processing attainment, which we don't

62:44 time to discuss the function. But you have varying effects. There are

62:48 interesting more from metric changes that are and the take home message is that

62:53 will have more from metric changes have reported between normal individuals and those that

62:59 migraines. And you'll also have more network changes that have been reported.

63:04 we have decided by the nurse versus migrant workers that have much more

63:10 higher frequency and repetition of this migraine on the functional imaging, you can

63:18 a distinction here in typical predictable than of and when we talk about the

63:26 imaging, I believe this is with , which is blood oxygenation level dependent

63:32 . I because we're still metabolic in hunt. We're tracking, tracking camera

63:37 activity changes and had positron emission tomography is typically based on glucose turnover in

63:45 Tabernacle. But you can see increases one s one temporal power, surprised

63:52 directed activity. That means the migrant haven't increased bold activity signal already.

63:59 there blows a little bit more active like the nurse and this is what's

64:05 on. Um So I'm not going go over all of these differences.

64:12 obviously there is a good and they here. Feel free to discuss and

64:17 important. But also there's a gabba two. If you think about some

64:24 may be between cellular mechanisms of seizures according to spreading depression, you're now

64:32 there is some sort of a shortcut . There's maybe some sort of a

64:37 . This organization sponsored sensor service. affecting certain parts of the brain but

64:44 is also due to this increased potentially metabolic or yawning this regulation you

64:53 an increase with the names and you decreased. Yeah, I want and

65:00 is also where the distance of the and inhibitory balance that we discussed and

65:06 we're discussing here. What are some the medications for for we've for

65:14 So what is litigation used to relieve pain or his best when taking the

65:21 sign of an ongoing migraine and sit the sand. Acceptable project to there's

65:28 the reasons for my parents and we'll talk about it is the main reason

65:36 migrants is genetic reasons there is a situation because by the things but I

65:45 it in my family. So my also has my agreements and she has

65:51 whole routine as soon she also gets As soon as she sees these visual

65:59 she drops whatever it may be going because We cannot wait for longer than

66:06 five minutes. You know she starts the same issues of not seeing or

66:13 able to speak properly and you know don't want to be around people didn't

66:19 so drops whatever she's doing. She's a class or she's you know cooking

66:27 or walking her dog and she immediately her pain medications, pain relievers,

66:35 turns all eyes off all sound She puts black hat then cover over

66:44 eyes and she relaxes and a lay position. And if there is situations

66:54 moments actually there are migrating attacks that can stop. Well you don't have

67:01 and you have You have 10:15 minutes get home. You're driving in a

67:08 that that is you know to take medication you know that can be really

67:18 , not recommended to drive for If there is an urgent education's trip

67:25 calcitonin, gene related peptide receptor opioid help campaign and anti nausea drugs do

67:37 people buy it off and also experience that's related to migrants, preventive medications

67:45 migrants. What pressure lowering medications, depressants, anti seizure drugs and that's

67:54 of the old reliable two of the mechanisms simply talk interestingly enough Botox

68:02 That's the regulation of the civil Colin Tony and gene related C.

68:09 R. P. Monoclonal antibiotic So there are several solutions for

68:18 So I don't I think there are cures but some of them are very

68:25 and some of us are treating it pain relievers. There are two energy

68:33 ah bump, a noise are quite ah And alternative preparations. So just

68:45 but just CBD because there is evidence financial resources and mention of campaign.

68:53 yeah so taking medication right away and everything drawing making a salsa quite often

69:04 somebody to. So I've had situations my my migraine attack that's so bad

69:12 I couldn't dial my phone because I see that the dial pad. So

69:21 know if you if I had a to feel it maybe but then you

69:26 sensitivity and numbness. People also feel around her face and that's associated with

69:34 trigeminal ganglion complex that we'll talk about probably not today because I'm running out

69:42 time but we'll come back and review few more slides on on this sparkling

69:48 the trigeminal ganglion complex. Okay but what what happens if you wait too

69:55 then you're helpless You know that because cannot style how so what you do

70:03 you take the medication Surly and actually speaks for whatever attack you're having you

70:10 anxiety attacks. Panic attack. Tremor uh spasm attack because it could be

70:18 spasms or it could be pulmonary spasms will be shutting down or breathing.

70:27 you only have a certain amount of . So typically, and even with

70:32 and people say, oh, it's a headache. Okay, don't go

70:35 er headache. You don't feel like cannot do much, you know,

70:40 hours or sometimes in a day or after. You have a headache.

70:45 not a headache. We don't have us all those 1/3, but

70:51 So you alert somebody. So you yourself in a quiet space century and

71:00 organization. Darkness can call somebody hey, I'm having a migraine

71:07 The detail over at home and I checked on this evening medication should typically

71:14 acting just like with edibles Within 15 , 20 minutes, half an

71:20 That's why when you swallow any you have to wait for it to

71:24 this modern media. Okay, I'm end the lecture here today. We've

71:30 through pretty much all of the I wanted to share with you that

71:34 that I've uploaded. I want to with you also an additional slide on

71:40 causes of the most important emerging cause migrating as uh, as the familial

71:48 . And then moved into Alzheimer's disease COVID-19 and see how much we can

71:54 at that time. So all thank you all very much. And

72:04 hope to see you in person on , I'm

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