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dasitmane

Bit of an idea for possible CURE. Has some weight to it.

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No, the article clearly shows that the excitotoxity is a result from 5htp2a receptor activation.

did you even read the study?

Edited by dasitmane

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Pretty much puts the nail in the coffin for me at this point. We know have numerous studies showing proof of cell death from multiple hallucinogens. Now how we get this information to the general public is the real question...

I don't get why the 5htp2a receptor needs to be activated in order for the cell death to occur though. That's serotonin, correct? 

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On 2/13/2018 at 8:04 PM, K.B.Fante said:

Pretty much puts the nail in the coffin for me at this point. We know have numerous studies showing proof of cell death from multiple hallucinogens. Now how we get this information to the general public is the real question...

I don't get why the 5htp2a receptor needs to be activated in order for the cell death to occur though. That's serotonin, correct? 

Yah, I'm not exactly sure either to be honest. But its clearly the link.

I do wish this information was publicized instead of the ridiculous researchers investigating the "pros" of hallucinogens, if this information were available I never would have done them.

Edited by dasitmane

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Today, I'm the bearer of bad news. This news was unforeseen, and is all in all, quite crushing. Looking through regenerative videos of salamanders today, I found and noticed that regeneration wasn't completely up to par. That even though the limb might regrow. It didn't grow back perfectly in most cases. Which had me wondering more about neuronal regeneration, and after just a little bit of reading, the reality of all of this has really, finally, and sadly, fallen in to place. Unless someone can prove me wrong.

I'm actually so depressed about this, that Ill hardly elaborate like I usually do. But to put it plainly, the brain consists of neurons, and as most of you might know, neurons have axons, what I failed to realize in the beginning of this 6 year escapade, is that those axons in certain areas of the brain, are actually quite long. Take for example the picture of the brain that I have uploaded, the long strands are actually called axonal tracts, theyre long communicative groups of axons from neurons. When the neurons die, the axon dies.

Heres where we lose. When these neurons are replaced with new neurons, the new neurons, do not and can not connect to the same long distance axonal path that was originally there. Rather, the newly generated neurons are primarily bound to attach its axons to the surrounding neurons. Thus not completely repairing the original function of the brain, even if humans could regenerate neurons.

This proof can be seen in this article of the axolotl salamander, in the link posted. Also, dont be confused by the title, neuronal diversity is the main topic of the article, but they elaborate on these long distance axonal tracts not being able to reconnect due to the distance. Its a lot like even if humans could regenerate limbs, if you severed a ligament it would detach from the bone, and even though it could regenerate, or have the ability, it does not have the ability to reach out and reattach itself to the site it was originally attached to. This has to be performed by a surgeon. 

I do beg everyone to read this thoroughly to see if I have made any mistakes in my understanding. Granted I know that some recovery is possible. But its fairly evident our brains will never be the same.

https://elifesciences.org/articles/13998

 

Adult axolotls can regenerate original neuronal diversity in response to brain injury

 

Abstract

The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species.

https://doi.org/10.7554/eLife.13998.001
Open annotations (there are currently 0annotations on this page).

eLife digest

Humans and other mammals have a very limited ability to regenerate new neurons in the brain to replace those that have been injured or damaged. In striking contrast, some animals like fish and salamanders are capable of filling in injured brain regions with new neurons. This is a complex task, as the brain is composed of many different types of neurons that are connected to each other in a highly organized manner across both short and long distances.

The extent to which even the most regenerative species can build new brain regions was not known. Understanding any limitations will help to set realistic expectations for the success of potential treatments that aim to replace neurons in mammals.

Amamoto et al. found that the brain of the axolotl, a species of salamander, could selectively regenerate the specific types of neurons that were damaged. This finding suggests that the brain is able to somehow sense which types of neurons are injured. The new neurons were able to mature into functional neurons, but they were limited in their ability to reconnect to their original, distant target neurons.

More research is now needed to investigate how the axolotl brain recognizes which types of neurons have been damaged. It will also be important to understand which cells respond to the injury to give rise to the new neurons that fill the injury site, and to uncover the molecules that are important for governing this regenerative process.

https://doi.org/10.7554/eLife.13998.002

Introduction

Under physiological conditions, the neurogenic capacity of the adult mammalian brain is largely restricted to two neurogenic niches, the subventricular zone of the lateral ventricle, which gives rise to interneurons of the olfactory bulb and the subgranular zone of the dentate gyrus, which generates granule cells of the hippocampus (Ming and Song, 2011). Neurons in other brain regions are only generated during embryonic development and are not replaced postnatally.

In contrast to mammals, other vertebrates are endowed with superior capacity to regenerate multiple organs, including parts of the central nervous system (CNS). Among these, urodele amphibians like the axolotl (Ambystoma mexicanum) are endowed with the capacity to add new neurons to the brain throughout life (Maden et al., 2013) and can regenerate the spinal cord and parts of the brain after mechanical injury (Burr, 1916; Kirsche and Kirsche, 1964a; Butler and Ward, 1967; Piatt, 1955). Resection of the middle one-third of one hemisphere, but not the whole hemisphere, in the axolotl telencephalon results in reconstruction of the injured hemisphere to a similar length as the contralateral, uninjured side (Kirsche and Kirsche, 1964a; Kirsche and Kirsche, 1964b; Winkelmann and Winkelmann, 1970). Similarly, after mechanical excision of the newt optic tectum, new tissue fills the space produced by injury (Okamoto et al., 2007). Interestingly, in the newt, selective chemical ablation of dopaminergic neurons within a largely intact midbrain triggers regeneration of the ablated pool of neurons (Berg et al., 2010; Parish et al., 2007). In addition to urodeles, teleost fish have also been extensively studied for their capacity to regenerate the CNS and have led to the identification of some of the molecular signals involved in the regenerative process (Kizil et al., 2012). These studies highlight the value of regenerative organisms as models to understand the mechanisms that govern brain regeneration for possible application to the mammalian brain.

However, the mammalian CNS is notoriously complex, and its ability to compute high-level functions, like those of the mammalian cerebral cortex, relies on the presence of a great diversity of neuronal subtypes integrated in specific long-distance and local circuits and working within a defined tissue architecture. Disruption of brain structure, connectivity, and neuronal composition is often associated with behavioral deficits, as observed in models of neurodevelopmental, neuropsychiatric, and neurodegenerative disease. It is therefore likely that functional regeneration of higher-order CNS structures will entail the regeneration of a great diversity of neuronal subtypes, the rebuilding of original connectivity, and the synaptic integration of newborn neurons in the pre-existing tissue. It is not known to what extent even regenerative species can accomplish these complex tasks, beyond their broad ability to generate new neurons and to rebuild gross brain morphology. It remains therefore debated whether any vertebrates are capable of true functional brain regeneration.

Using the adult axolotl pallium as the model system, we have investigated whether a diverse array of neuronal subtypes can regenerate and whether their tissue-level organization, connectivity, and functional properties can also regenerate after mechanical injury.

In contrast to the teleostean pallium, the everted nature of which makes linking distinct regions to their mammalian counterparts difficult (Northcutt, 2008), the gross neuroanatomy of the axolotl pallium, organized around two ventricles, shows clear similarities to that of the mammalian telencephalon. In addition, while the evolutionary origin of the mammalian cerebral cortex remains controversial (Molnár, 2011), it is likely that the axolotl pallium contains a basic representation of several of the neuronal subtypes found in the mammalian cerebral cortex and thus may serve as a good model for investigating regeneration of neuronal heterogeneity and complex circuit function.

Here, we demonstrate that both pre- and post-metamorphosis adult axolotls are able to regenerate a diversity of neurons upon localized injury to the dorsal pallium. This process occurs through specific regenerative steps that we defined in live animals using non-invasive magnetic resonance imaging (MRI). Strikingly, newborn neurons can acquire mature electrophysiological properties and respond to local afferent inputs. However, they unexpectedly fail to rebuild long-distance circuit and the original tissue architecture.

The data provide the first proof for the precision with which axolotls regenerate a diverse set of neurons, which in turn become electrophysiologically active and receive local afferent inputs. Notably, however, our results also challenge prior assumptions of functional brain regeneration in salamanders by uncovering unappreciated limitations in the capacity of adult axolotls to fully rebuild original long-distance connectivity and tissue organization, a finding that redefines expectations for brain regeneration in mammals.

axonaltracts.jpg

Edited by dasitmane

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I don't get how you arrived at your conclusion from reading this article. A), we don't know what part of the brain is affected in HPPD. If it's the hippocampus then this articles doesn't really apply because it's well documented to be one of the few areas of the brain where neurogenesis is proven to occur. But again, we don't know this either way. And B), this article doesn't say anything about humans in particular or mention anything about how certain brain regions cannot recover from damage, only that it's not known how many regions are capable of neurogenesis.

Traditional brain science is almost getting turned over on a daily basis. Things that were considered set in stone even a few years ago are frequently up for debate with every passing study. It's well established that different parts of the brain connect and overlap when compromised, so even if HPPD results in cell death in brain areas that aren't well studied there's no need to believe they can't be fully healed. 

The problem with seeing this article as proof that we're out of luck is the simple fact that people who get HPPD do fully recover -- many, in fact. This has been well documented on this site and across the Internet. Though it takes many years for neurogenesis to run its course the countless recovery stories on this site alone are all the proof you need that whatever part of the brain is affected by HPPD clearly has the ability to regrow or reconnect and execute the functions it performed prior to damage. 

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The part of the brain that is effected is any area involving serotonin receptors. Which are very specific neurons that are compromised throughout the entire brain. The damage is very widespread.

This research disregards neurogenesis, so the hippocampus is a mute point.

Yes the axolotl brain is an animal brain, but is still compromised of the same cells, and similar architecture. Also, the axolotl is the absolute best example that we have of regenerative ability. If it cant do it, we definitely wont be able to.

The brain may do quite a bit, but it wont fully recover, even with neurogenesis. The study clearly shows that newly made neurons are incapable of reconnecting the long distance axonal growths that previously existed.

Give those who recovered enough coffee and they will realize they haven't recovered. People adapt, people will even lie to themselves that they are fine to get on with their day, day after day. Their neuronal loss maybe wasn't nearly as bad as those who dont "recover". All cases recover to a degree, but massive brain trauma according to what im seeing here can only be repaired to a certain degree and by the laws of nature herself will never repair to 100% functionality. Not from what I can see.

What you're saying is possible, that the brain can reconnect, is exactly what this study shows is not possible. The neurons that are newly generated simply just dont know to send their axons 2mm or more. The brain simply just wont reconnect like it was.

Sorry. I did my best.

Edited by dasitmane

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This should be the areas most effected by hallucinogens. The purple are all the neurons the most likely will die due to excitotoxic apoptosis. The purple areas are regeneratable. The red areas are the axons of these neurons branching out to other areas of the brain. Those axons are non regeneratable. So even under the circumstance of neurogenesis these serotenogenic channels are inhibited or cut off from their original areas of communication.

it should be noted too that the main area effected is the midbrain, which is associated with vision, hearing, motor control, sleep/wake, alertness, and temperature regulation.

the medulla also is strongly effected, which is critical in regulating heart rate, one symptom I definitely had was that my pulse went from 60s and 70s to 90s and 100s.

34B2D1D8-1D42-4588-9975-838596F0B5FB.jpeg

Edited by dasitmane

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The only possible loop hole in all this would be if for some strange reason in cases of neuronal apoptosis the axonal tracts are still maintained. Which I doubt would be likely. 

Edit: in the two Neuro degenerative diseases that i looked at, axonal tract death is synonymous with neuronal loss.

Edited by dasitmane

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One point too that deserves mention is Dr. Abraham mentions possible excitotoxic loss of interneurons. This is definitely probably a case being that they are shown to be excited by 5ht2a receptors. Which can be seen here in this study https://www.ncbi.nlm.nih.gov/pubmed/8819525. It would also explain the high activity recorded in hallucinogen use in the neocortex, which contains about 30% interneurons. Primarily relay ones with long axons, so non regeneratable. 

LSD and the phenethylamine hallucinogen DOI are potent partial agonists at 5-HT2A receptors on interneurons in rat piriform cortex.

Abstract

Correlations between 5-hydroxytryptamine (5-HT) receptor binding affinities and human hallucinogenic potency have suggested that 5-HT2 receptors mediate the hallucinogenic effects of lysergic acid diethylamide (LSD) and phenethylamine hallucinogens. Electrophysiological studies have suggested that a subpopulation of gamma-aminobutyric acid (GABA)ergic interneurons in layer III of the rat piriform cortex are excited by serotonin (5-HT) via 5-HT2A receptors. These interneurons have inhibitory inputs on pyramidal cells in layer II. In the present study, we tested low concentrations of both LSD (3-100 nM) and the phenethylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI; 0.3-10 microM) on rat piriform cortical interneurons that were excited by 5-HT. Both LSD (3-100 nM) and DOI (0.3-10 microM) excited almost every cell excited by 5-HT. The maximal excitation achieved with LSD and DOI was 39% and 55% of the effect of a near-maximal 5-HT concentration (100 microM). Consistent with a partial agonist action, LSD and DOI blocked the 5-HT excitation of piriform cortical interneurons only at the higher hallucinogen concentrations tested. A specific 5-HT2A receptor antagonist, MDL 100,907, blocked excitation of these interneurons by 5-HT, LSD and DOI, but not by norepinephrine or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate. Again, consistent with a partial agonist action of the hallucinogens, intracellular experiments showed that a maximal concentration of DOI (10 microM) induced fewer postsynaptic inhibitory currents than did 5-HT (100 microM) in pyramidal neurons in layer II of the piriform cortex. Based on the present electrophysiological studies, we conclude that LSD and DOI, a phenethylamine hallucinogen, act as highly potent partial agonists at cortical 5-HT2A receptors.

Edited by dasitmane

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Anyone even reading all this?

At this point the only way out of this is if most of the excitotoxic damage is axonal related, and doesn't go in to wallerian degeneration, somewhat like multiple sclerosis. Then I could there being massive recovery. But its not looking likely.

Edited by dasitmane

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Another interesting note is that I made a huge mistake in my early research, thinking that axonal repair in the central nervous system is the same as in the peripheral, this is quite untrue however. Axons in the central nervous system are very limited to their ability to repair. Basically now im going over everything again to make sure I haven't made any mistakes and have already found a huge one. Im also going to get my MRI and review it as well. Heres an article that describes axonal recovery in the central nervous system and how limited it is.

If the case is just axonal damage, and the axons dont die, it should be easily recoverable. But Im pretty skeptical at this being the case. Heres the article though

http://www.brc.cam.ac.uk/principal-investigators/james-fawcett/axon-regeneration-in-the-central-nervous-system/

Axon Regeneration in the Central Nervous system

Many forms of brain and spinal cord (CNS)  damage cut axons. Where axons can regenerate, as in peripheral nerves, they can bring back function. However in the CNS axon regeneration fails. This is the main reason why paralysis and loss of sensation is permanent in conditions such as spinal cord injury. Many laboratories are therefore working to find out how to make it possible for cut axons in the spinal cord and brain to regenerate. Axon regeneration in spinal injury patients is one of the best hopes of returning useful function. Axon regeneration in the CNS fails for two reasons. First because the environment surrounding CNS lesions is inhibitory to axon growth, and second because most CNS axons only mount a feeble regeneration response after they are cut. The Fawcett laboratory is working on both these problems.

Edited by dasitmane

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I went and got a copy of the information of my MRI today, a lot of people report that their MRIs are normal. But i want to challenge everyone that has had one done to check their MRI reports and note the specifics. I was told my MRI was fine. But in reality, looking at the report, there are scattered nonspecific white matter hyperintensities. Hyperintensities in MRIs show changes in the white matter, and could be axonal damage such as demyelination, axonal loss, and neuronal loss.

Im trying to learn as much about this as I can. If our damage is only "irreversable" demylination, our condition is actually potentially reversible.

I dont have much hope at this point though.

Edited by dasitmane

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This study gives some hope that the axon terminals are still intact and the the main route of damage is demyelination.

 

Toxic Leukoencephalopathy

Many toxic brain disorders preferentially affect the cerebral WM.145 A spectrum of severity has been described, ranging from mild, reversible confusion, to coma and death, with concomitant MRI and neuropathological WM changes.145 Cranial irradiation and cancer chemotherapeutic drugs, most notably methotrexate146,147 (Fig. 12), are leukotoxic, an effect that complicates the treatment of many malignancies.

Figure 12
FLAIR MRI in the axial plane of a patient with cognitive decline after receiving methotrexate.2

Toluene leukoencephalopathy (TL) is an intriguing disorder that convincingly illustrates the ability of pure WM damage to produce dementia.148152 Toluene (methylbenzene) is a common household and industrial solvent and is the major solvent in spray paint. It is abused by millions of people worldwide for its euphorigenic effect, an abuse that has a lifetime prevalence in the United States estimated at 18%.152 The intentional inhalation of toluene, often for years without respite, results in a dramatic syndrome of dementia, ataxia, and other neurologic signs.149,150 The effects are readily detectable on MRI and include diffuse cerebral and cerebellar WM hyperintensity (Fig. 13). The degree of cerebral involvement strongly correlates with the severity of dementia, which is the most prominent manifestation of the syndrome.148,150 Autopsy studies of TL reveal selective myelin loss that spares the cerebral cortex, neuronal cell bodies, and even axons in all but the most severe cases.151,152 TL thus ex-emplifies the toxic WM disorders and stands out as a convincing example of WM dementia (WMD).6,116,153

Figure 13
T2-weighted MRI appearance in the axial plane of toluene encephalopathy in two patients (A, B).

Inhalation of heated heroin vapor (colloquially termed “chasing the dragon”) produces a devastating, progressive spongiform leukoencephalopathy. The MRI appearance154156 is highly suggestive, if not pathognomonic (Fig. 14). Cocaine use may produce similar findings, including symmetric and widespread involvement of the posterior cerebral hemispheric WM, cerebellar WM, splenium of the CC, and brain stem (medial lemniscus and lateral brain stem), with sparing of the deep cerebellar nuclei. MRS in areas of parenchymal damage demonstrates elevated lactate and myoinositol, reduced NAA and creatine, normal to slightly decreased Ch, and normal lipid peak. Neuropathologically this is WM spongiform degeneration with relative sparing of U-fibers, whereas electron microscopy reveals intramyelinic vacuolation with splitting of intraperiod lines. Preservation of axons with no evidence of Wallerian degeneration, inflammatory cellular reaction, or demyelination is taken to indicate that axons may be relatively spared, consistent with the degree of recovery in some cases.154 Clinical manifestations include cerebellar motor findings of ataxia, dysmetria and dysarthria, bradykinesia, rigidity, and hypophonia, and the syndrome may progress over weeks to pseudobulbar palsy, akinetic mutism, decorticate posturing, and spastic quadriparesis. Death occurs in approximately 20% of cases. Clinical and MRI findings can progress after cessation of drug use, indicating that the toxic exposure precipitates an evolving injury. The lack of concordance between MRI perfusion and spectroscopy may reflect impaired energy metabolism at the cellular level. The lactate peak on MRS; mitochondrial swelling and distended endoplasmic reticulum in oligodendrocytes on autopsy; and apparent response to antioxidants and mitochondrial cofactors such as vitamin E, vitamin C, and coenzyme Q suggest mitochondrial dysfunction as a basis for this entity.154,155,157

Figure 14
MRI scans after heroin inhalation, known colloquially as “chasing the dragon.” FLAIR images in the axial plane (AD). Corresponding 1H MRS imaging spectra in two of the images show characteristic lactate peak and decreased NAA. ...

Other toxin-induced spongiform leukoencephalopathies with fluid accumulation restricted to myelin sheaths include those precipitated by cuprizone, ethidium bromide, actinomycin D, triethyl tin, hexachlorophene, isonicotinic acid, hydrazine, and cycloleucine.154,158

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So recently K. B. Fante brought to my attention the possibilities of the parasympathetic and sympathetic nervous system being involved. And after some discussion, thought, and contacting Dr. Abraham, its pretty clear that Dr. Abraham must not have meant the interneurons in the brain, but rather the interneurons of the spinal column. I dont have the initial report from Dr. Abraham's commentary that I had found in a book involving toxicological pathologies, but ill try to find it. He basically expressed that the interneurons are believed to play a critical role, a lot being that they are highly involved in GABA and glutamate release. This would have a direct modulation on the parasympathetic and sympathetic nervous system, nay, it seems to be one of the primary regulating components.

From Wiki, spinal interneurons

https://en.wikipedia.org/wiki/Spinal_interneuron

Neurotransmitter

The sensory information that is transmitted to the spinal cord is modulated by a complex network of excitatory and ihibitoryinterneurons. Different neurotransmitters are released from different interneurons, but the two most common neurotransmitters are GABA, the primary inhibitory neurotransmitter and glutamate, the primary excitatoryneurotransmitter.[9][10] Acetylcholine is a neurotransmitter that often activates interneurons by binding to a receptor on the membrane.[11]

One of the things that Dr. Abraham mentions is that this may be why GABA agonists(benzos) are beneficial.

 

We might have our guys. The best part about this is they are located in the CNS spinal column, which means there will be no scar tissue, AND they are primarily grey matter neurons, which means short axons and densely populated neurons, giving room for possible regeneration.

It would also explain the anxiety in HPPD, related to the sympathetic nervous system that K. B. Fante noted.

And would explain why brain MRIs come back for the most part, normal.

I dont know of anyone that has had spinal MRIs that have HPPD....

Also it lines up with the study that I think I posted, but did find that relates specifically to interneurons being excited by 5ht2a receptors, aka hallucinogenic use.

Edited by dasitmane
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Glutamate, GABA and acetylcholine are the three neurotransmitters that have come up time and time again in my Google searches based on my symptoms either improving or worsening. I made a post about glutamate a while back here:

http://hppdonline.com/topic/5453-glutamate/#comment-34490

And one about the category of vegetables called nightshades, which are anticholinergic, which you can find here:

http://hppdonline.com/topic/5431-nightshades/#comment-34336

I also made one about caffeine and its inhibitory affect on GABA:

http://hppdonline.com/topic/5371-negative-reaction-to-caffeine/#comment-33944

All these categories of foods make my symptoms worse. If these transmitters are the fuel for the interneurons of the parasympathetic and sympathetic nervous systems then it only makes sense that the foods they're found in have an enormous effect on HPPD symptoms. 

One area of interest I'm increasingly warming to is the vagus nerve, which controls parasympathetic nervous system function. The vagus nerve runs to many different parts of the body and specifically controls stomach function, which I've had terrible problems with recently. A diet high in sugar can damage the vagus nerve and cause damage to the blood vessels that carry oxygen and nutrients to the nerves. Well, I've had a very high sugar diet over the course of the last year as well as prediabetes due to an under-active thyroid (also connected to the vagus nerve) and all of a sudden my visual symptoms have gotten increasingly worse. In the past I've had symptom flare ups due to diet (mostly caffeine and nightshades), however once my stomach problems began my visual symptoms have gotten significantly worse and stayed that way 24-7. 

The vagus nerve controls exhalation, which I find interesting considering I had a very difficult time laughing when I first got HPPD. It was as if I couldn't breathe or exhale properly. This has improved over time but I thought it was really strange at first. It would make sense if my vagus nerve was damaged that I couldn't exhale properly, as laughing is a strictly exhaling activity. 

I know tinnitus is a commonly shared symptom for many of us. There is a connection between the vagus nerve here as well, as shown in this study where stimulation of the vagus nerve resulted in decreased tinnitus:  http://www.utdallas.edu/news/2011/1/13-8021_Findings-Show-Promise-in-Battle-Against-Tinnitus_article.html

I can't remember where I posted it but my first introduction to the vagus nerve was through this article, which links it to depersonalization -- another shared HPPD symptom -- and provides ways to stimulate it: https://www.selfhacked.com/blog/28-ways-to-stimulate-your-vagus-nerve-and-all-you-need-to-know-about-it/

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That would be unfortunate if cell death occured and the new-built neurons would be incapable of connecting with each other properly again. Is there some good way to measure if cell death occured in one's brain? And how long would neurons need to regrow and build new connections after apoptosis set in?
Hope these questions had not already been discussed.

Edited by fruitgun

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9 hours ago, fruitgun said:

That would be unfortunate if cell death occured and the new-built neurons would be incapable of connecting with each other properly again. Is there some good way to measure if cell death occured in one's brain? And how long would neurons need to regrow and build new connections after apoptosis set in?
Hope these questions had not already been discussed.

It would be extremely unfortunate. Normally in that instance it would be most notable of their inability to reconnect in axonal tracts, which are long and throughout the brain. The best way we have to measure or detect neuronal loss in a living subject is an MRI. Which apparently for the most part, most peoples HPPD related MRIs come back normal.

In the case of neurogenesis which does not happen naturally in the human brain on a large scale, it would most likely take 3 months to get a decent amount of new neurons, and I would assume 1 to 2 years for the most regrowth that you will get. Granted even in neurogenesis its unlikely that there will be 100% recovery. Even the liver when resected though it regenerates usually will only account for 90% of the size it originally had. 

If there is neuronal loss in the gray matter, there are no axonal tracts there, and the neurons are much more densely populated with short axons, regeneration of these areas would be much more notable for functional recovery.

There are also potentials for axonopathic toxicity, where only the axons would be damaged for the most part and suffer extreme demyelination, in this case everything in my opinion would be mostly recoverable. Some toxins act mostly on the axons, others, like glutamate, directly on the neuronal bodies. I dont know what 5 HT receptors act directly on yet, but I do know they alter glutamate production, which leads for potential in neuropathic toxicity. I do not know yet if neurons over produce glutamate under influence of hallucinogens.

If anyone can find answers to those questions it would be extremely appreciated.

Edited by dasitmane

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2 hours ago, dasitmane said:

It would be extremely unfortunate. Normally in that instance it would be most notable of their inability to reconnect in axonal tracts, which are long and throughout the brain. The best way we have to measure or detect neuronal loss in a living subject is an MRI. Which apparently for the most part, most peoples HPPD related MRIs come back normal.

In the case of neurogenesis which does not happen naturally in the human brain on a large scale, it would most likely take 3 months to get a decent amount of new neurons, and I would assume 1 to 2 years for the most regrowth that you will get. Granted even in neurogenesis its unlikely that there will be 100% recovery. Even the liver when resected though it regenerates usually will only account for 90% of the size it originally had. 

If there is neuronal loss in the gray matter, there are no axonal tracts there, and the neurons are much more densely populated with short axons, regeneration of these areas would be much more notable for functional recovery.

There are also potentials for axonopathic toxicity, where only the axons would be damaged for the most part and suffer extreme demyelination, in this case everything in my opinion would be mostly recoverable. Some toxins act mostly on the axons, others, like glutamate, directly on the neuronal bodies. I dont know what 5 HT receptors act directly on yet, but I do know they alter glutamate production, which leads for potential in neuropathic toxicity. I do not know yet if neurons over produce glutamate under influence of hallucinogens.

If anyone can find answers to those questions it would be extremely appreciated.

I posted an article a while back about Robert Sapolsky and there might be some relevant information in there pertaining to this subject. You can find that whole post here: 

http://hppdonline.com/topic/5604-article-on-robert-sapolsky-stress-the-brain-etc/#comment-35473

The biggest thing with all this seems to be how much stress you were under prior to, during and after your inciting incident that gave you HPPD. It seems anxiety is the real killer in all this as it completely compromises your brain's ability to fight off disease and heal properly after injury. Here's a good quote from the article above on this topic: 

"The hippocampus is the most glutamate using part of the brain. This is so because learning and memory are so vital to survival that this excitoneurotransmitter is used liberally in this area. The energy crisis to the neurons created by excess glucocorticoids means the neuron doesn’t have adequate energy for reuptake of calcium and glutamate. It is through this lack of cleanup that these chemicals hang around longer; thus increasing calcium release into the cytoplasm, which produces enzymes that increase free radical damage to the cytoskeletal membrane of the cell, thereby bringing about cell death or apoptosis. To protect themselves from excitotoxin damage the neurons produce adenosine, GABA, taurine, heat shock proteins, antioxidants, feedback inhibition of Ca++ flow and increase glucose and lactate uptake to improve energy levels of the neurons. However glucocorticoids interfere with these defense mechanisms also."

As Dasitmane says, if HPPD is cell death of some sort whether you recover depends largely on how much damage occurred in the first place. If it was merely the dendrites then you can surely rebuild, but if the cell body itself suffers then you're less likely to experience regrowth. But again, much of this depends on the type of drug, how much, anxiety, proper recovery, where in the brain or body the damage occurs, etc. I think it's safe to say that as long as you refrain from doing drugs again, live a healthy lifestyle, eliminate stress and do all the things necessary to promote growth inside your body that you give yourself an excellent chance at a near or complete recovery.

I know in my case I've had all kinds of health issues after getting HPPD (everything from benzo withdrawals to anxiety to sugar addiction to thyroid issues to digestive complications to depression, heartbreak, you name it) and yet I've never had any major setbacks that I haven't been able to recover from. It's the exact same theory as trimming a plant or a flower: If you just clip the buds or part of the stalk it will grow back again and again, but if you start damaging the root then you risk killing it for good. In this same vein, nature knows which direction to move for a reason. Flora grow towards the sun due to photosynthesis and dendrites grow towards other dendrites for neurochemical benefits. I think the idea they would grow back and have no idea where to grow or connect to doesn't make a lot of sense, but this is just my opinion on the matter and I could be dead wrong. 

A few more paragraphs on this topic:

"For our growth, development, health and fulfillment we need stimulation rich environments...what this stimulation amounts to would differ between us monkeys...some would like more toys, others more playmates, others would want a bigger playground etc...

Big Fun is an attempt to generate more stimulating conditions in which growth is possible. Our brains form a million new connections for every second of our lives, revealing the huge importance of our everyday experiences in making our brains what they are. Boredom makes us stupid--the richness of our environment affects our brain structure. With a more stimulating environment our brains develop denser neuron growth and increase the amount of certain synaptic proteins that the brain uses to relay messages between neurons... 

When it comes to brainpower they say you either use it or lose it. Fred Gage of the Salk Institute for Biological Studies studied the hippocampus, a brain region involved in learning and memory and skills and found that activation of NMDA receptors affects the survival of brain cells. This study in mice suggests that the survival of newly formed adult brain cells depends on the amount of input they receive, via NMDA receptors - proteins that sit on the surface of brain cells and help them communicate with each other, suggesting that communication is essential for neuron survival. http://www.newscient...-job-to-do.html... 

This suggests that our interpersonal world, (how well we bond and communicate with others, whether we are repressed and if we easily forgive or hold grudges,) might also have a parallel in how well our own neurons communicate with each other and thereby impact the lifespan of those neurons. This resilience of neurons that communicate well with each other might also be key in how we each respond differently to stress and PTSD. Brains that are repressed or weak in self-communication might be more vulnerable to the effects of glucocorticoids and to neuron damage in general."

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Cool thing to note here as well is that glutamate, acting directly on the neuronal bodies, causes neuropathic toxicity, where as chemicals acting on the axons, generally cause axonopathic toxicity, and generally aside from extreme cases, leaves the neurons intact, localizing damage specifically to the axons. 5 HT for as far as I can find act specifically on the synapses. This leads to higher potential for axonopathic toxicity. Granted, 5 HT receptors do regulate glutamate, so glutamate still could be the end product of an excitotoxicity cascade.

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