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More on notch inhibition and hair cells.

http://www.pnas.org/content/112/1/166



That is what the gamma secretase inhibitors are inhibiting, notch signalling.

https://en.m.wikipedia.org/wiki/Notch_signaling_pathway

There are many natural inhibitors of notch signalling that have been identified that may be safe enough to ingest orally to achieve high enough concentrations in the blood to accumulate in the endolymph in the cochlea to initiate mitotic proliferation of new hair cells. The study on mice with ly411575 states they were given it orally and it regrew their hair cells, but it was toxic to them.

Natural notch inhibitors:

Cowanin derived from the plant
Garcinia Speciosa
https://www.nature.com/articles/s41598-018-23698-4

Uscharin derived from plant
Calotropis gigantea
https://pubs.acs.org/doi/abs/10.1021/acs.jnatprod.7b00282

Xanthahumol
Derived from the female inflorescences of plant Humulus lupulus
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127464

The plant Nerium indicum contains 8 notch inhibitor compounds
https://pubs.acs.org/doi/abs/10.1021/acs.jnatprod.7b01031?journalCode=jnprdf
 
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Good point, that's an assumption. Music I've been listening too for years pretty much sounds the same. Songs I play on guitar sound the same. That being said I'm pretty sure I used to be able to hear up to 18-20khz and now I'm deaf past 16khz. My T matches those high frequencies too.
your tinnitus is super ultra hihg frequency?
 
your tinnitus is super ultra hihg frequency?
I have two tones. One is medium high and very faint mostly in my left ear. Theres another one that is like 16khz and higher that comes and goes and makes my brain feel like its being sliced with a light saber that sounds like a dog whistle. If I get good sleep it can be gone almost all day. I didnt sleep enough last night and its here today. When I wake up with it, it lasts all day. The sound that did it was from this phase effect on my 2×12 guitar combo amp and it has very high frequency characteristics that match the frequency of my T. This leads my to believe I did kill the hair cells associated with those frequencies and my brain is filling in the lost input with T at those frequencies. This shitz driving me crazy and I'm desperate to find a cure, hense my research efforts.
 
losing a lot of hearing is why you developed tinnitus in the first place.
Don't know for sure but I think some deaf people have no tinnitus and some do. Removing the cochlea does not guarantee termination of T, I've googled this but found no definitive answers. Imagine being totally deaf with severe tinnitus, a situation I would never risk being in.
 
Don't know for sure but I think some deaf people have no tinnitus and some do. Removing the cochlea does not guarantee termination of T, I've googled this but found no definitive answers. Imagine being totally deaf with severe tinnitus, a situation I would never risk being in.
so you can't hear much above 4k? you have 85dbT and you don't believe hearing loss is associated with your tinnitus?
 
someone needs to research the effects GABA has on the development and treatment of tinnitus instead of fucking more TRT/CBT-esque reports.
 
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noxacusis (painful hyperacusis) is related to cochlear damage directly.

The researchers that study know tinnitus is obviously evident in the brain due to changes in the DCN
 
@Contrast I apologize if I am refering to certain things incorrectly because I am not a scientist.

I see you make many posts regarding GABA in the brain. What are your thoughts on glutamate / glutathione levels? I would think that glutamate being known to cause oxidative stress and inflammation in the brain could play a big roll in tinnitus. It could be that glutamate causes inflammation in the auditory system, auditory nerve or DNC, which could make someone more susceptible to developing tinnitus because they auditory system is inflammed / damaged or it can cause the DNC to become more active /sensitive causing it to become overactive.

I can't remember where, but i remember reading somewhere that people with tinnitus are more likely to also have anxiety disorders (before onset of tinnitus). It has been well documented that people who suffer from anxiety disorders have higher glutamate levels and lower glutathione levels than a "normal" person. We all know the glutathione plays a very important roll in keeping our ears healthy and safe. Several studies have shown that NAC, which increase glutathione levels in the brain, helps regulate glutamate in the brain as well and has been shown to decrease hearing damage in loud environments when compared to control groups.

I feel it is more of a glutamate / glutathione issue, which is causing the problem, than a GABA one. I feel GABA, having a sedative effect, helps relax people and making their tinnitus perception decrease. I very well may be wrong, but I think this is a interesting topic.
 
@JohnAdams Im so sorry i can't research with you, im super busy building a website for my friends.

I'm a graphic artist with a lot of responsibilities
 
so you can't hear much above 4k? you have 85dbT and you don't believe hearing loss is associated with your tinnitus?
I first noticed tinnitus in my early twenties and wrote it off as benign like eyeball floaters. It got louder and pulsed with my heart when I jogged, again, no big deal. When I had vertigo, ENT told me I had hearing loss, I didn't really care, it was the vertigo causing me big problems. I did notice one day when I used my cell phone, I couldn't hear in one ear like the other. No big deal, use the other ear and/or use speaker phone always.
Guess I'm now learning the correlation between hearing loss and tinnitus but still uncertain of a direct and proportional relationship.

Also, I can hear above 4k just need higher volume. I don't quite understand frequency, volume, tones of treble and bass. Easy stuff but at this point learning about acoustics doesn't help directly with my tinnitus issues as much as other subjects related to the psychology of coping.

But I'm now learning more here. Still I think some people have zero hearing and no tinnitus like Rush Limbaugh possibly and others?
 
I first noticed tinnitus in my early twenties and wrote it off as benign like eyeball floaters. It got louder and pulsed with my heart when I jogged, again, no big deal. When I had vertigo, ENT told me I had hearing loss, I didn't really care, it was the vertigo causing me big problems. I did notice one day when I used my cell phone, I couldn't hear in one ear like the other. No big deal, use the other ear and/or use speaker phone always.
Guess I'm now learning the correlation between hearing loss and tinnitus but still uncertain of a direct and proportional relationship.

Also, I can hear above 4k just need higher volume. I don't quite understand frequency, volume, tones of treble and bass. Easy stuff but at this point learning about acoustics doesn't help directly with my tinnitus issues as much as other subjects related to the psychology of coping.

But I'm now learning more here. Still I think some people have zero hearing and no tinnitus like Rush Limbaugh possibly and others?
Rush Limbaugh has tinntius.
 
There's an older youtube video made after Rush received his implant. William Shattner curiously asked Rush about tinnitus, being a sufferer himself. Rush's answer wasn't too convincing that he had tinnitus. Shattner is a sufferer, Rush I'm not too sure.
he said his tinnitus comes and goes in that video
 
reversing hearing loss should reduce tinnitus. read what i posted in the hair cell regeneration thread.

When the cilia are destroyed they pickup no vibrations. The brain misses these vibrational signals and tries to replace the input own its own, apart from the cochlear mechanisms.

So... if the cochlea is removed, these new neural pathways formed within the brain remain a circuit that produces hallucinogenic sound independent of the cochlea.

Restoring these missing vibrations of the cilia to cancel the hallucinogenic sound of neural circuits is something I have not considered.
 
Please read the scientific papers I have posted here. All of them. We need to become scientists and research towards a cure. This is some life and death shit right here. Please for the love of God. I'm begging you guys.
 
Please read the scientific papers I have posted here. All of them. We need to become scientists and research towards a cure. This is some life and death shit right here. Please for the love of God. I'm begging you guys.
JohnAdams I seriously love you and I'm going to give you my legit response. I'm too am dying for a cure, no less. But I do not think I'd be able to find one without a full-fledged advanced research team, super equipment and a of course huge budget for efficacy trials and the like. As you well know the human body is massively complex and the potential for error is a direct offshoot of that. That (and the massive bureaucracy of course) is why effective medicines and cures are so expensive to develop.
I do, however like to closely follow research currently being conducted e.g. FX.
Take care bro.
 

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