TNF Alpha and Brain Inflammation

Hello,

Humour me. I was watching a program on tv tonight that featured the use of a drug that has traditionally been used to treat rheumatoid arthritis (an immune modulator). The drug in question; Enbrel, is now being applied to the treatment of stroke in the states, and trials are commencing in Australia next year. Researchers interviewed in the program stated that they felt Enbrel is an exciting drug with potential for more widespread use in neurodegenerative conditions. Whilst tinnitus wasn't specifically mentioned, I cant help but wonder if addressing brain inflammation by reducing TNF alpha (as in the case of Enbrel) would be helpful? Are there any threads on this forum on this topic? Has there ever been a link made between raised TNF and tinnitus? Pardon my ignorance.

Dr google revealed a bunch of info on brain inflammation. I found some possible hypotheses for the generation of brain inflammation ..

. an increase in TNF alpha causes an increase in AMPAR (a neuronal receptor for glutamate) which leads to an increase in glutamic receptors, causing an increased sensitivity in surrounding tissue, and hence increased neuronal excitability.

. TNF alpha mediated inflammation leads to changes in the properties of helper brain cells (astrocytes) which regulate glutamic acid, leading to a loss of glutamic acid regulation, causing an oversensitisation of neurons.

. Other theories include: the suppression of the production of new hippocampus neurons (neurogenesis), and decrease in the microglial cell's normal ability to repair and maintain neuronal synapses.

So, where am going with all of this?

1. could immune modulators like Enbrel/other have a role to play in treating tinnitus assuming brain inflammation is involved?

2. what are the ways in which TNF alpha can be reduced?

3. Can changes in neurons (ie increased sensitivity to neurotransmitters) be reversed? Can synapses be repaired?

any thoughts?

 

did you research this more? are you onto something here?

 

No, I haven't researched it more yet......WOrk has kinda taken over my time again but I will...

 

Dramatic headline incoming by Mail Online:

"Drug to reduce brain inflammation CURED tinnitus in mice - paving the way towards a pill for humans"

• The condition was stopped in mice by blocking a protein that fuels brain inflammation
• The Arizona team are hopeful it will lead to a gene therapy to combat tinnitus and other hearing loss disorders
• More information: Wang W, Zhang LS, Zinsmaier AK, Patterson G, Leptich EJ, Shoemaker SL, et al. (2019) Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models. PLoS Biol 17(6): e3000307. doi.org/10.1371/journal.pbio.3000307

A pill to cure the misery of tinnitus could be on the horizon following a breakthrough by scientists. The debilitating condition was stopped in mice by blocking a protein that fuels brain inflammation. The US team are hopeful it will lead to a gene therapy to combat ringing in the ears and other hearing loss disorders.

The study, published in the journal PLOS Biology, suggests it is caused by a molecule called TNF-A (tumor necrosis factor alpha) that disrupts communication between neurons. Blocking it pharmacologically also prevented tinnitus in lab rodents that developed the condition after being exposed to loud noise for two hours. The findings suggest neuro-inflammation may be a therapeutic target for treating tinnitus and other hearing problems, said the researchers.

Study co-author Dr Shaowen Bao said: 'Genetic knock out of TNF-A or pharmacologically blocking its expression prevented neuro-inflammation and ameliorated the behavior associated with tinnitus in mice with noise induced hearing loss.' Analysis showed inflammation in a sound-processing region of the brain controls ringing in the ears in the affected mice that have noise-induced hearing loss.

Analysis showed inflammation in a sound-processing region of the brain controls ringing in the ears in the affected mice that have noise-induced hearing loss. Dr Bao, a neuroscientist at the University of Arizona, said: 'Hearing loss is a widespread condition that affects approximately 500 million individuals, and is a major risk factor for tinnitus - the perception of noise or ringing in the ears.'

Recent research suggests hearing loss causes inflammation - the immune system's response to injury and infection - in the auditory pathway. But its contribution to hearing loss-related conditions such as tinnitus is still poorly understood. Dr Bao and colleagues examined neuro-inflammation - inflammation that affects the nervous system - in the auditory cortex of the brain following noise-induced hearing loss, and its role in tinnitus, in the rodent models.

He said: 'The results indicate noise-induced hearing loss is associated with elevated levels of molecules called proinflammatory cytokines and the activation of non-neuronal cells called microglia - two defining features of neuroinflammatory responses - in the primary auditory cortex.'

Dr Bao added: 'These results implicate neuro-inflammation as a therapeutic target for treating tinnitus and other hearing loss related disorders.' But he pointed out that although the therapy was successful in the animals, its potential adverse affects need to be thoroughly investigated before any human trials.

 

:O

 

Awesome find! Even if this drug were to have adverse effects, there could always be an attempt to redesign just like Dr. Tzounopoulos is redesigning trobalt to LR-81.

 

Causing brain inflammation is definitely not benign and could lead to serious, severe, cognitive impairments on the long term, such as it has been demonstrated on multiple occasions by pathologies causing similar effects, this leads me to be rather skeptical about this drug, but if it does work and the side effects end up minimal, it's worth looking into and would provide great relief to a lot of sufferers.

 

@Autumnly so what happens now? Seems like they haven't even started a trial yet.

 

DMSO is very effective at rapidly reducing brain inflammation, and according to my understanding, has become the drug of choice in ERs to immediately administer for closed head injuries. The drugs they used previously apparently didn't even come close to matching the effectiveness of DMSO, which is being credited with saving many lives.

 

I think there’s something here. How can you get T from hearing loss, neck problems, sporadic with good hearing, drugs, and I’m sure other methods. We know it’s in the brain somewhere, I hope the Univ of Arizona is working quick on this. Maybe these electrical devised are doing this on a small scale, like a tens unit internally zapping the inflammation down. But maybe it only works to a degree. This site should be hounding these Arizona professors as much as Neuromod. Maybe I’ll start.