Fawkinchit

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.

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.

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.

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. Marek GJ1, Aghajanian GK. Author information 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.

Did anyone end up uploading their mris? Can you guys that posted and had an mri please upload them?

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.

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.

Highly unlikely.

Heres the link tot he original study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861602/ Ive also attached an image of the neuronal tracts. That everyone can have an idea of what they are and or look like.

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.

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.

Thats weird, nicotine makes mine worse.

Whatever you do dont do any hallucinogens again, even if the symptoms reside. You should see some recovery. The degree no one will know for sure. Give it about 6 months. It took a while but eventually my visual snow went away. Primarily now I just have really bad anxiety issues.

lol

Jesus man 48 years?? I dont think I even plan on sticking around if I cant find a cure for this.

If you read my posts in the possibility of and idea for a cure thread, theres a great deal of answers and evidence of whats going on. The biggest problem is people just want to have fun and wont put time in to researching this.

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.

No, the article clearly shows that the excitotoxity is a result from 5htp2a receptor activation. did you even read the study?

https://www.ncbi.nlm.nih.gov/pubmed/22983118 more proof that hallucinogens cause neuronal excitotoxic apoptosis. Also note at the end that when the receptors are blocked it aids in the prevention and even halting of apoptosis. So antagonists should be a treatment in emergency cases of hallucinogen treatment, in ERs that is. The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons. Capela JP1, da Costa Araújo S, Costa VM, Ruscher K, Fernandes E, Bastos Mde L, Dirnagl U, Meisel A, Carvalho F. Author information Abstract 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA (100-800 μM) or DOI (10-100 μM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based (MTT) assays revealed a concentration- and time-dependent neuronal death and mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a significant increase in caspase-8 and caspase-3 activities. At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA. In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons. Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an irreversible antagonist) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators. Death was dependent, at least in part, on the stimulation of the 5-HT(2A)-receptors.

More evidence for glutamate related overexcitoxicity.

The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons. Capela JP1, da Costa Araújo S, Costa VM, Ruscher K, Fernandes E, Bastos Mde L, Dirnagl U, Meisel A, Carvalho F. Author information Abstract 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA (100-800 μM) or DOI (10-100 μM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based (MTT) assays revealed a concentration- and time-dependent neuronal death and mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a significant increase in caspase-8 and caspase-3 activities. At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA. In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons. Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an irreversible antagonist) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators. Death was dependent, at least in part, on the stimulation of the 5-HT(2A)-receptors. This basically proves that apoptosis from hallucinogenic overdose is a key factor.

Sounds like you are a bit paranoid. Its not impossible, but it will take time to see if you have it. Based on what you are describing if you do have it its very mild. If youre paraplegia is caused by brain abnormalities rather than spinal it could make you more susceptible. Basically give it some time and see what happens. Basically though, DO NOT do hallucinogens again. They definitely do serious damage to the brain.

A Recent Discovery MDMA and MDA cause neurons to release a neurotransmitter called serotonin. Serotonin is important to many types of nerve cells, including cells that receive sensory information and cells that control sleeping and emotions. The released serotonin can over activate serotonin receptors. In animals, MDMA and MDA have been shown to damage and destroy nerve fibers of neurons that contain serotonin. This can be a big problem, because serotonin neurons have a role in so many things, such as mood, sleep, and control of heart rate. Scientists have recently found that the damaged serotonin neurons can regrow their fibers, but the fibers don't grow back normally. The fibers may regrow into brain areas where they don't normally grow, but not into other brain areas where they should be located. The new growth patterns may cause changes in mood, learning, or memory.

Lol thanks Jay. How have you been? Synapse plasticity most likely wouldn't be the case here, its a temporary condition and easily rectifiable. Im still leaning towards neuronal loss, be it whatever the route, and likened to that in lithium overdose.

6 years Edit: Man some people have had this a long time! I dont get the visual snow, dp/dr, or any visuals. I used to get the snow and dp/dr but they went away. Never had visuals. For me most of mine is manifested by a crippling anxiety, its almost unbearable, and just about anything can trigger it. As long as im not exposed to anything and dont drink too much coffee it typically ok. But to much coffee in the morning can make it bad. And some times it flares up and I dont have an explanation.