25 replies to this topic

[pi-]

I think I've found a molecule that can be orally administered that restores critical period plasticity.

 

It is in this 2011 patent here: Nogo Receptor Binding Small Molecules to Promote Axonal Growth
Stephen M. Strittmatter <-- this guy is a key player

 

Three years ago. So that means probably someone has manufactured it.

 

If not, is there anyone in this community with the power to manifest it? Calling all big fish that swim deep! Please PM or post!

 

Here is a summary of my research to date.

 

Firstly, animals have critical periods during which key brain wiring happens. Hubel and Wiesel received the 1981 Nobel Prize in Physiology or Medicine for showing that if you cover one eye of a mouse between days 20 and 32, it never learns to use that eye. But either side of that window there is no lasting damage. Actually it was kittens but I can't remember the window numbers. They use mice now.

 

The brain is inherently plastic; but the degree of plasticity is controlled region by region. There is some meta-plasticity machinery at work that solidifies structure over time, allowing our basic functions (motor, cognitive, linguistic, ...) to be resilient and efficient through becoming hardwired.

 

Neuroscientists such as T K Hensch used this finding to uncover these meta-plasticity mechanisms that underlie critical periods. Syringe out braincells before during and after compare chemical composition. Then figure out what is at the root of the cause/effect cascade.

 

One of the main players is Nogo66-receptor (NgR) on the surface of the axon.

 

(I take it you know that the brain is a bunch of neurons each of which has an axon and several dendrites. Each of these looks like a tree. Axons and dendrites connect via synapses. Electric pulse goes out of the  axon and gets picked up in the dendrites.)

 

As the brain ages, oligodendrocyte cells sent out tendrils that wrap myelin sheaths around axons (and dendrites for that matter). This myelin secretes three messagers (Nogo, OMgp, MAG), all of which activate NgR, which launches the signalling cascade that inhibits further growth of the axon (through destroying its growthcone).

 

However, if you can somehow disable this NgR,  then axons won't stop growing.

 

Does this lead to a persistent critical period?  The way to find out is to breed NgR-knockout mice (that receptor is just some protein, so they locate it's coding sequence in the DNA and cut it out. How? MAGICK!) and do the eyepatch thing. It works!

 

So, how to disable NgR?

 

I'm not sure exactly how they found this out, but they did find out that certain HDAC inhibitors have this effect. VPA (Sodium Valproate), a HDACi (class 2 I think -- grateful if anyone can tell me), has the effect of disabling NgR to some extent.

 

Time for a human experiment?  Valproate reopens critical-period learning of absolute pitch. In fact that paper is what started me off researching a couple of months ago. So everything I've written here -- that paper was the starting point for me!

 

Slightly dodgy results in that experiment. Nevertheless I tried it myself. VPA causes inflammation of my lungs, painful breathing, I had to stop. Apparently this is a known side effect that affects <1%. My shit luck. Bollocks. Fuckadiddle. etc.

 

So either I need another (class 2?) HDACi, or I need to specifically disable NgR. That's how I found the patent paper this morning.

 

Let me explain briefly HDAC inhibition, so that I can offer some explanation of what's going on in that paper.

 

 DNA winds around spools called HISTONES. DNA contains the codes for ~22k proteins, molecular machines attach at specific points and copy the section for a particular protein's coding sequence (this blueprint then gets sent out of the nucleus, built into the actual protein).  HDACi involves molecules attaching onto the tails of these histones that reduce their electrical charge, so the DNA loses its tight grip on the spool, and this means the transcription machine get round it. Sometimes HDACi is medicated for cancer because the DNA is wound too tight "kill a cell" messenger proteins can't get created, and cells don't get killed.

 

I've put up a starter kit for learning HDACi on my wiki http://mathpad.wikidot.com/hdaci

 

So HDACi results in increased for transcription rates of a ton of proteins.  One of them disables NgR. But which one?

 

If you look on that patent paper, you'll see that they start out with a test for whether a particular protein disables NgR. Then they throw a whole load of molecules through this test, patenting the winner(s). They don't say where they get these candidates from, but I'm guessing they are throwing every protein on the DNA strand through.

 

NOTE: be warned, I'm a computer programmer by trade by the way, with no experience in biology/chemistry/neurology. I've had to stop coding due to strain injuries, which gives me a lot of time for reading some papers and learning. I'm about six weeks in. So if I say something that reveals my understanding is completely wrong, please put me right!

 

π

Edited by pi-, 19 August 2014 - 12:25 AM.

[StevesPetRat]

You could try fistfuls of butyrate to get around your valproate reaction.

Sounds interesting but the whole "destroyed growthcone" thing makes me hesitant. Would it be a bit like giving HGH to someone whose growth plates are fused?

[middpanther88]

Good research! Thank you!

[pi-]

@StevesPetRat, Butyrate is Class I, I have a feeling I need Class 2.  I did investigate Butyrate and it came up short.

 

Remember, experiments have been done successfully on mice and men, and knocking out NgR just results in a critical period that does not close. I don't see what you are worried about... maybe you can dig into the science so as to articulate clearly?  You may find in so doing that the worry evaporates.

 

@middpanther88, Glad you like it!  Don't forget to give me a badge!  I love badges, they are almost as good as hard cash

[StevesPetRat]

Not worried, I just don't see how knocking out Nogo in an adult could trigger axon growth when the growth cones are destroyed already.

Perhaps I fundamentally misunderstand adult neurogensis; I thought new synapses can be generated whenever, new neurons grow in regions of the hippocampus and striatum, but no new axons are grown past a certain age. This is hardly something I'm sure of, though.

Something like this, increasing expression of genes GAP-43 and CAP-23 to get the growth cones to regenerate, should be helpful too:
http://www.nature.co.../nn0101_38.html

Still very interested in your findings as I had untreated (albeit mild) sleep apnea most of my life http://jnnp.bmj.com/.../5/685.full.pdf
(Not to mention the booze...)

[serp777]

More neurons and axons doesn't always = good and smarter. Sometimes it just means schizophrenia or less efficient brain structures. THe brain is more complicated than that. 

Edited by serp777, 19 August 2014 - 03:21 AM.

[pi-]

@StevesPetRat, I haven't looked deeply into exactly how disabling NgR promotes axon regeneration/sprouting.  But it is in the literature. Difficult to find, I've just spent an hour searching without getting anything comprehensive.

 

However, several oblique references, for example (again from Prof. Strittmatter):

 

Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury

Limited axonal plasticity within the central nervous system (CNS) is a major restriction for functional recovery after CNS injury. The small GTPase RhoA is a key molecule of the converging downstream cascade that leads to the inhibition of axonal re-growth. The Rho-pathway integrates growth inhibitory signals derived from extracellular cues, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein, Ephrins and repulsive guidance molecule-A, into the damaged axon. Consequently, the activation of RhoA results in growth cone collapse and finally outgrowth failure. In turn, the inhibition of RhoA-activation blinds the injured axon to its growth inhibitory environment resulting in enhanced axonal sprouting and plasticity. This has been demonstrated in various CNS-injury models for direct RhoA-inhibition and for downstream/upstream blockade of the RhoA-associated pathway. In addition, RhoA-inhibition reduces apoptotic cell death and secondary damage and improves locomotor recovery in clinically relevant models after experimental spinal cord injury (SCI).

 

The abstract continues with an interesting statement that ibuprofen enhances plasticity(!):

 

Unexpectedly, a subset of "small molecules" from the group of non-steroid anti-inflammatory drugs, particularly the FDA-approved ibuprofen, has recently been identified as

(1) inhibiting RhoA-activation,

(2) enhancing axonal sprouting/regeneration,

(3) protecting "tissue at risk" (neuroprotection) and

(4) improving motor recovery confined to realistic therapeutical time-frames in clinically relevant SCI models.

 

Here, we survey the effect of small-molecule-induced RhoA-inhibition on axonal plasticity and neurofunctional outcome in CNS injury paradigms. Furthermore, we discuss the body of preclinical evidence for a possible clinical translation with a focus on ibuprofen and illustrate putative risks and benefits for the treatment of acute SCI.

 

This is very strange, I have never heard of this cited as an effect of ibuprofen. There is another paper on the same subject: Ibuprofen enhances recovery from spinal cord injury by limiting tissue loss and stimulating axonal growth

 

@serp777, what are you doing? Have you just written down the first thought that came into your head? Why do you think we are interested in that? I spent several weeks organising my own thoughts before posting. At least spend a few minutes to check that what you're saying makes sense and contributes to the discussion.

[pi-]

I found another interesting paper: Membrane-type Matrix Metalloproteinase-3 Regulates Neuronal Responsiveness to Myelin through Nogo-66 Receptor 1 Cleavage

Strittmatter again.

 

MTxMMP (x in 1,2,3,4,5) is manufactured inside the neuron, and persuades it to shed it's NgR-s.

 

The paper doesn't suggest whether MTxMMP may have potential as a future safe drug.

 

I emailed Prof. Strittmatter asking whether any of the NgR-disabling molecules he has identified are sourceable, and got a brief reply saying that they are currently undergoing animal testing.

[serp777]

@StevesPetRat, I haven't looked deeply into exactly how disabling NgR promotes axon regeneration/sprouting.  But it is in the literature. Difficult to find, I've just spent an hour searching without getting anything comprehensive.

 

However, several oblique references, for example (again from Prof. Strittmatter):

 

Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury

Limited axonal plasticity within the central nervous system (CNS) is a major restriction for functional recovery after CNS injury. The small GTPase RhoA is a key molecule of the converging downstream cascade that leads to the inhibition of axonal re-growth. The Rho-pathway integrates growth inhibitory signals derived from extracellular cues, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein, Ephrins and repulsive guidance molecule-A, into the damaged axon. Consequently, the activation of RhoA results in growth cone collapse and finally outgrowth failure. In turn, the inhibition of RhoA-activation blinds the injured axon to its growth inhibitory environment resulting in enhanced axonal sprouting and plasticity. This has been demonstrated in various CNS-injury models for direct RhoA-inhibition and for downstream/upstream blockade of the RhoA-associated pathway. In addition, RhoA-inhibition reduces apoptotic cell death and secondary damage and improves locomotor recovery in clinically relevant models after experimental spinal cord injury (SCI).

 

The abstract continues with an interesting statement that ibuprofen enhances plasticity(!):

 

Unexpectedly, a subset of "small molecules" from the group of non-steroid anti-inflammatory drugs, particularly the FDA-approved ibuprofen, has recently been identified as

(1) inhibiting RhoA-activation,

(2) enhancing axonal sprouting/regeneration,

(3) protecting "tissue at risk" (neuroprotection) and

(4) improving motor recovery confined to realistic therapeutical time-frames in clinically relevant SCI models.

 

Here, we survey the effect of small-molecule-induced RhoA-inhibition on axonal plasticity and neurofunctional outcome in CNS injury paradigms. Furthermore, we discuss the body of preclinical evidence for a possible clinical translation with a focus on ibuprofen and illustrate putative risks and benefits for the treatment of acute SCI.

 

This is very strange, I have never heard of this cited as an effect of ibuprofen. There is another paper on the same subject: Ibuprofen enhances recovery from spinal cord injury by limiting tissue loss and stimulating axonal growth

 

@serp777, what are you doing? Have you just written down the first thought that came into your head? Why do you think we are interested in that? I spent several weeks organising my own thoughts before posting. At least spend a few minutes to check that what you're saying makes sense and contributes to the discussion.

Perhaps you should use this drug for your short term memory, as you seem to completely forget what you wrote. Clearly the point of this substance is to increase plasticity and axon growth. Look where you wrote:

 

 

"However, if you can somehow disable this NgR,  then axons won't stop growing."

 

And look where you write: "

 

"So, how to disable NgR?"

 

Is axon growth always a good thing? No--the brain sometimes reduces the number of neurons and axons in order to do processing more efficiently for a given task. 

[StevesPetRat]

Is axon growth always a good thing? No--the brain sometimes reduces the number of neurons and axons in order to do processing more efficiently for a given task.

I've heard of synaptic pruning but not axonal pruning - are you sure the latter is common? Also, axons are quite sensitive to inflammatory damage from things like hypoxia, trauma, chemicals, and autoimmune disease. Depending on one's circumstances the benefits of reversing such damage might exceed the risks of interfering with pruning. And surely such a drug would be pulsed, anyway.

[somethingstrange]

I think this would be more axons/dendrites growth would be beneficial only for people who experienced malnutrition/negligence in childhood or some developmental disorders.

[pi-]

It is true that as the cortex matures mechanisms set in to protect and optimise existing structure. Neuron/Neurite/Synapse pruning, myelination, etc.

 

This results in an adult homeostasis that is difficult to reverse.

 

Reopening the critical period will in many ways be an anti-nootropic.

 

However I am interested in rewiring my brain at a low level. If temporarily losing efficiency is the price to pay, so be it!

 

π

[somethingstrange]

I hope you will find the answer but bear in mind that reopening critical period is not sufficient you need mental exercises to modulate/refine neural network ( this applies to artificial networks too ).

Found interesting info on wiki

"The cholinergic and glutamatergic systems in the brain serve an important role in learning, memory, and the developmental organization of neuronal circuitry. These systems help to capitalize on the critical period and organize synaptic transmission. Autism and other learning disabilities have been targeted with drugs focusing on cholinergic and glutamatergic transmission. These drugs increase the amount of acetylcholine present in the brain by increasing the production of acetylcholine precursors, as well as inhibiting acetylcholine degradation by cholinesterases. By focusing on heightening the activity of this system, the brain's responsiveness to activity-dependent plasticity is improved. Specifically, glutamatergic drugs may reduce the threshold for LTP, promote more normal dendritic spine morphology, and retain a greater number of useful synaptic connections. Cholinergic drugs may reconnect the basal forebrain with the cortex and hippocampus, connections that are often disrupted in patients with learning disorders."

[pi-]

@labratdream, yes, but stimulus and LTP-enhancing-noots are the next level up. First you have to generate neural structure, then you have to train it.

 

@StevesPetRat, remember this axon-growth inhibition only kicks in once the neural structure has matured. Think homeostasis! As neurite structure matures, tendrils come out from nearby oligodendrocyte cells, which wrap myelin sheaths around these neurites. These sheaths emit messenger molecules (NogoA, MAG, OMgp) which get picked up by the NgR on the surface of the neurite, which goes through RHO->ROCK->... and results in sabotaging the ability of acting microfilaments to form structure.  And that is how growth cones grow -- by these microfilaments dynamically extending scaffolding.

 

So in the hippocampus, I would imagine this process is in different stages depending on how close we are to the region where new neurons get generated (dentate gyrus?)

Edited by pi-, 18 September 2014 - 03:00 PM.

[e Stone]

It is true that as the cortex matures mechanisms set in to protect and optimise existing structure. Neuron/Neurite/Synapse pruning, myelination, etc.

This results in an adult homeostasis that is difficult to reverse.

Reopening the critical period will in many ways be an anti-nootropic.

However I am interested in rewiring my brain at a low level. If temporarily losing efficiency is the price to pay, so be it!

π

[e Stone]

In other words. ..you can't teach an old brain new tricks. Additionally, brain size certainly doesn't = increased advantage especially in primates. Just look at cromagnon's voluminous braincase compared to ours. They had over 1 lb more brain matter than we do at present....

Just passing through.. good day!

Edited by e Stone, 25 November 2014 - 12:13 AM.

[wanderlust]

 Valproate reopens critical-period learning of absolute pitch.

 

after reading this paper  i orderd liver and kideny funtion tests  (every 2 weeks) and  began taking sodium valprate ,i then carefully intoduced  piracetam & dmae 

i then began spending one hour a day everyday on

http://www.lumosity.com/ & http://www.cambridgebrainsciences.com/

 

after 10 days my scores have inproved my 93% however this may infact be caused simply by my working hard and taking piricetam and dmae rather than the valproate .

 

in the same time period my moterbike's engine blew up . so as a beginner i set out to replace the engine, sprokets , chain , wheel barings, and more (expecting that i would have to take it to a garage when i failed) . i have worked on mecanical things before  on priacetam and dmae  with slight improvment. however this time .it was almost intuitive, as if i where learning somthing natural to me like walking. i was enjoying myself so much that i decided to stip  the bike down to a bare frame and then put it back to a working bike again insted of just fixing it which i did , i even replaced  the wiring loom the manufactures had put in as i knew could do a better job . my mecanical undersanding has incressed my ten fold , and was told i am a decent novice mecanic after 14 days of playing about with a bike

 

after 14 days i have stopped taking valproate and will be allowing my body 1 months rest before starting again .

 

i have taken a comprehensive check of my heatlh after and before which show my body as being heathy and happy

https://www.medichec...heck-PLUS_25MC/

 

i have also noiced a small lump below my ear (which i suspect is a tiny piece of  stainless steel shrapnel  ) however i need to have this checked out before continuing .

 

 

 

 

 

 

 

 

Edited by wanderlust, 09 February 2016 - 03:17 PM.

[Sleepdealer]

How did you get the sodium valproate? You have a prescription or you have another way?

 

And how are your mechanical skills and your overall learning skills holding up today?

 

This sounds like a potential treatment for stroke victims and others.

[medievil]

 Valproate reopens critical-period learning of absolute pitch.

 

after reading this paper  i orderd liver and kideny funtion tests  (every 2 weeks) and  began taking sodium valprate ,i then carefully intoduced  piracetam & dmae 

i then began spending one hour a day everyday on

http://www.lumosity.com/ & http://www.cambridgebrainsciences.com/

 

after 10 days my scores have inproved my 93% however this may infact be caused simply by my working hard and taking piricetam and dmae rather than the valproate .

 

in the same time period my moterbike's engine blew up . so as a beginner i set out to replace the engine, sprokets , chain , wheel barings, and more (expecting that i would have to take it to a garage when i failed) . i have worked on mecanical things before  on priacetam and dmae  with slight improvment. however this time .it was almost intuitive, as if i where learning somthing natural to me like walking. i was enjoying myself so much that i decided to stip  the bike down to a bare frame and then put it back to a working bike again insted of just fixing it which i did , i even replaced  the wiring loom the manufactures had put in as i knew could do a better job . my mecanical undersanding has incressed my ten fold , and was told i am a decent novice mecanic after 14 days of playing about with a bike

 

after 14 days i have stopped taking valproate and will be allowing my body 1 months rest before starting again .

 

i have taken a comprehensive check of my heatlh after and before which show my body as being heathy and happy

https://www.medichec...heck-PLUS_25MC/

 

i have also noiced a small lump below my ear (which i suspect is a tiny piece of  stainless steel shrapnel  ) however i need to have this checked out before continuing .

I dont see a point in taking a break of a hdac inhibitor unless you actually do notice tolerance, i beleive constant dosing produces the most benefits,

 

that said your results indicate that the hdac inhibition directly or indirectly acted or potentiated pathways that where allready functioning better then most ppl, kinda like how you push the first dominostone, if you dont they all stay standing up and then even if you have a brain thats capable of more you wont get the benefits

[William Sterog]

Curcumin seems to work as a HDAC inhibitor.

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo.

http://bmccancer.bio...471-2407-11-144

Although, it could be a bad thing:

Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity

 

http://journals.plos...al.pone.0134110

Edited by YOLF, 02 March 2016 - 07:24 PM.

[wanderlust]

,My mecanical skills .well i am currently designing a newkind of external combustion engine as i don't like how inefficant combustion engines are and i thought of a simple newkind of engine to drive an electric moter from any fuel source . such as wood ,oil , petrol ,  coal ,with out batterys ,  fun  times . it seemed obvious ,like anyone with any understanding of engines would see how to do it better.

my mecanical skills remain and are getting better natually and easily . its now a  talent i have

 

i continued the brian training excersises my scores continued to incress at roughly the normal rate  when i was only taking pracitam

 

 

After i stopped taking it my psychotherapist  stopped a session to ask me what had changed in my life  as i had been making fantastic progress toward being a " self-actualizing person" and was slowing down again. which was a big supprise
to me . i do feel better in myself but weekly psychotherapy and hours of brain training has that effect all by its self

 

 

I stop taking sodium valporite after such a short time  due to the hugh list of horrible side effects it can cause including death .

and due to getting a lump behind my ear ,under the skin which throbbed and  had remained and slowly incressed insize for a month. 

(it was a tiny peice of shrapnel as suspected)

 

blood tests showed my liver and kideny health as perfect from start to finish .

and any theorys as to why it had zero effect on learning the  brain training games but appeard to have effects on mecanical understanding . ?

 

i am considering taking sodium valporte along side injections of cerebrolysin any thoughts onthis ?

and if its a safe combination  .

 

 

with the addition of neurobiofeedback a type of biofeedback that uses real-time displays of brain activity—most commonly electroencephalography (EEG), to teach self-regulation of brain function.

 

i would be adding the addional saftey of having a psychotherpist monitoring my mental state with the ability to call a halt on the trial if needed . though he views my use of such things as dangerous, hes is willing to provide oversight .

 

 

i brought my sodium valporite from united pharmacies

Here in the uk its legal to have prescription drugs from outside of the uk. 

 

 

[wanderlust]

though incressed mecanical aptitude  and perhaps greatly boosted psychogical wellbeing are fantastic,  Using sodium valporite and brain training tools to "rewire" my brain . failed . I can retake the tests to confirm ,but i still have learning disabilies.

 

 could the phyical nature of mecanical engeering and the phyical nature of learing a to hear perfect pitch somehow  be related to how sodium valporite effects the brain , learning at the "critical period " is mostly done phyically , such as walking or talking , or riding a bike.

 

and if so perhaps the brain can be rewired with valporite and targeted  phyical learning , such learning to play the violin for incressed fine moterskills .or phyically playing chess for problem solving

 

[Sleepdealer]

 

My mecanical skills .well i am currently designing a newkind of external combustion engine as i don't like how inefficant combustion engines are and i thought of a simple newkind of engine to drive an electric moter from any fuel source

 

Is this a new side of you then, or is there a possibility that you have always had this sort of engineering-ish side to you to begin with and it just got potentiated by sodium valproate?

[wanderlust]

iv always thought mechines where intresting persay , but a year ago i couldn't start a lawnmower . 

i am thinking of learning caligrapthy  next  as a test

my hand writing is terrible dispite attempts at inproving it   i have zero level of skill or intrest in writing things in an ornate pretty way .

so its the perfect test . Plus i need to inprove my fine moterskills

 

 

 

 

 

 

[pi-]

Be very careful with Valproate.  Just one week of the stuff has permanently fucked my body up. Now I cannot consume tea, chocolate, tomato, alcohol, etc. It's really shit.

 

Really ask yourself why you are stuffing these chemicals into your body. If your life is not enough right now, how likely is adding chemicals to tip the balance?

 

Beware of the placebo effect. Give someone chalk tablets telling them they are brain pills, they will probably report improved cognition.

 

If you must do Valproate, make sure you are taking omeprazole, which blocks the signalling cascade that produces stomach acid.

 

Get a blood test done in advance that checks your eosinophil count. If noticeably above-average, DON'T DO IT!

 

π

[BieraK]

Catalpol from Rehmannia apparently is THE HERB for axonal growth, as we know Catalpol inhibitos Nogo-A but it also enchances GAP-43

https://en.wikipedia.../Gap-43_protein

 

Growth Associated Protein 43 also known as GAP43 is a protein that in humans is encoded by theGAP43 gene.^[3]

GAP43 has been termed a 'growth' or 'plasticity' protein because it is expressed at high levels in neuronal growth cones during development, during axonal regeneration and is phosphorylated after long-term potentiation (LTP) and after learning (reference needed). This protein is considered a crucial component of the axon and presynaptic terminal, its null mutation leading to death within days after birth due to axon pathfinding defects.^[4]

Here is the study

Lyophilized Powder of Catalpol and Puerarin Protects Neurovascular Unit from Stroke.

Author information

 

Abstract

Hunting for an effective medicine for brain stroke has been a medical task in neuroscience for decades. The present research showed that the lyophilized Powder of Catalpol and Puerarin (C-P) in all the tested doses (65.4 mg/kg, 32.7 mg/kg, 16.4 mg/kg) significantly reduced the neurological deficiency, infarct volume and apoptotic cells in ischemic/reperfusion (I/R) rats. It also promoted astrocyte processes and prolonged neuron axons in infarct area. Further, it decreased MDA, NO, NF-κB/p65, TNF-α, IL-1β and IL-6 and enhanced the EPOR and GAF-43. 65.4 mg/kg and 32.7 mg/kg C-P could up-regulated EPO and VEGF significantly. In vitro, 49 μg/mL and 24.5 μg/mL C-P decreased the leakage of sodium fluorescein and increased the activity of γ-GTP. Additionally, it increased SOD and decreased MDA, NO, and LDH and decreased NF-κB/p65, TNF-α, IL-1β and IL-6 and unregulated EPO, EPOR, VEGF, and GAP-43. Only the dose of 49 μg/mL increased TEER and Claudin-5 and turned the typically damaged morphologies of neurons, astrocytes and endothelium into a favorable trend. These data imply that C-P improved the recovery of neurological deficiency in motor, sense, balance and reflex, and protected the whole NVU by anti-oxidative stress, anti-inflammation and up-regulating some protective factors. This research provides a candidate medicine for brain stroke and, at the same time, a pattern for drug study targeting NVU in vitro.

 

Edited by BieraK, 13 May 2017 - 05:05 AM.