[jlpom]

This is cool but I don't see neural stem cells grafting and this hydrogel have clinical applications in humans, because the brain is very difficult to access, even via the CSF (diffusion is very limited), without very invasive way like trepanation.

I think a more realistic clinical approach is astrocytes to neurons reprogramming using vectors like AAV9 to pass the blood brain barrier and activate genes to convert them [1] to different types based on the genes (NGN2: glutamatergic, ASCL1: GABAergic, dopaminergic, cholinergic...). This has the added benefit of reduced cancer risk (direct reprogramming) and astrocytes have a regional identity [2].

[1]: https://www.embopress.org/doi/full/10.15252/emmm.202114797 [2]: https://www.science.org/doi/full/10.1126/sciadv.abe8978

[derefr]

> because the brain is nearly inaccesible, even via the CSF (diffusion is very limited), without very invasive way like trepanation.

If transorbital lobotomy is possible, presumably transorbital endoscopic hydrogel injection would also be possible, no?

Also, what about “going in through the out door” — entering the lymphatic system at the neck, and then endoscoping up into the brain’s glymphatic channels, and further back into the brain itself?

[Rastonbury]

What about neurons/nerves in the spine or eye?

[jlpom]

Spine: intrathecal or systemic via AAV9 (eg. Zolgensma) injection ; Eye: don't know

[moremetadata]

I'll stick with my mega doses of algal oil derived omega-3s they are not so fishy in taste or burps.

Of all the tissues in the body, retina contains the highest concentration of the omega-3 fatty acid (FA), docosahexaenoic acid (DHA). Up to 60% of the total FA in rod outer segment membrane phospholipids is DHA [1]. If you suffer from night blindness something that happens as we age, DHA improves the ability to see in low light conditions. [2]

The brain has the second highest lipid content behind adipose tissue, and brain lipids constitute 50% of the brain dry weight [3]. DHA makes up over 90% of the n-3 PUFAs in the brain and 10%–20% of its total lipids. DHA is especially concentrated in the gray matter [4]

After a 6month study researchers found DHA levels had increased by 200% with the spinal fluid content only increasing by 28% [5]. This study also didnt look at the effect of tyrosine in the substantia nigra which besides increasing the pheomelanin and eumelanin, that area of the brain also acts an antioxidant or filter for metals in the brain. [6]

What is ignored with omega 3 is the role it plays with neutrophils, if you have a lot of pathogens, your neutrophil numbers will go up which will reduce the amount of omega-3's which can go to the brain, because Omega-3 supplementation increases the EPA+DHA content of neutrophil membranes [7] which improves their function at sensing pathogens and interactive with other parts of the immune system. [8,9,10,11] especially when considering todays levels of air pollution from things like fossil fuels.

I'd also increase choline content for the brain [12] and alveoli gas exchange which improves physical performance and recovery rates. Some consider Choline should be consider essential nutrition, [13] but chemo brain fog, covid brain fog and baby brain pregnancy fog are all considered to be a deficiency in choline, and whilst the connections between neurons disappear, a stump is left on the neuron so when enough choline enters the diet, the connections can reform and you can get your memories back.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601701/#:~:tex....

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206354/

[3] https://www.frontiersin.org/articles/10.3389/fendo.2017.0006....

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772061/#:~:tex....

[5] https://www.nutraingredients.com/Article/2020/07/27/Pilot-st...

[6] https://www.sciencedirect.com/science/article/abs/pii/S03043...

[7] https://www.medrxiv.org/content/10.1101/2021.10.22.21264656v...

[8] https://www.youtube.com/watch?v=438EovW4tzs&ab_channel=NIAID

[9] https://www.youtube.com/watch?v=T4KJDIcx03

[10] https://www.youtube.com/watch?v=I_xh-bkiv_c

[11] https://www.youtube.com/watch?v=muoXWTv2QRw&ab_channel=Heinr...

[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585560/#:~:tex....

[13] https://lpi.oregonstate.edu/mic/other-nutrients/choline