Some info on nerve damage / ALS / multiple sclerosis / neurodegeneration / myelin disorders

[cs3000]

(oligodendrocytes & Schwann cells repair myelin and signal growth factors , but in ALS they are impaired) https://www.futuremedicine.com/doi/10.2217/nmt.14.21

in ALS, reduced ability of the new oligodendrocytes to myelinate axons and to give trophic support to neurons

vitamin b5 (pantothenic acid)
Vitamin B5 (d-pantothenic acid) localizes in myelinated structures of the rat brain: Potential role for cerebral vitamin B5 stores in local myelin homeostasis
b5 supports myelin.
especially its used in high amounts in the brain for myelin. (ALS effects myelin & motor neurons)


so one approach could be looking for things that support repair of myelin,

thyroid hormone is needed for myelin . good core temperatures?

https://selfhacked.com/blog/myelin/
^ some more ideas there e.g Maybe vitamin D, iodine if deficient, thyroid t3 if low , etc

Grape Seed Procyanidins Extract helps myelination Effects of Grape Seed Proanthocyanidin Extracts on Peripheral Nerves in Streptozocin-Induced Diabetic Rats

After being treated by GSPE, the severe segmental demyelination was decreased and Schwann cells were improved

increases BDNF , which may not be good in cases like ALS, depending on severity of disorder


Lithium / lithium orotate.
lithium supports myelin repair. increases bdnf, probably lowers neuroinflammation like the other lithium form
Lithium orotate works in lower doses vs tradition form of carbonate because it probably crosses BBB and works in the CNS better
see -> https://onlinelibrary.wiley.com/doi/pdf/10.1002/brb3.2262

https://journals.lww.com/nrronline/...promotes_proliferation_and_suppresses.29.aspx

Lithium promotes remyelination by Schwann cells and improves peripheral nerve regeneration.

Peripheral nerve injury is a common clinical problem that may affect a patient’s sensation, movement, gland, or organ functions. After peripheral nerve injury, Schwann cells, which are the major glial cells of the peripheral nervous system, undergo dedifferentiation, activation, and proliferation.
Proliferated Schwann cells migrate toward the injured nerve stumps, eliminate axon and myelin debris, and form a regenerative tunnel known as the band of Büngner to guide axon regrowth.
Schwann cells then differentiate and myelinate the regenerated axons to facilitate the functional recovery of the injured peripheral nerve

Investigations of the underlying mechanisms of lithium-induced peripheral nerve regeneration demonstrated that lithium can significantly affect the remyelination process. Lithium also increases the promoter activities, transcript levels, and protein levels of the myelin-related genes, peripheral myelin protein 22 and myelin protein zero, elevates the expression of remyelination transcription factors, Oct6 and Sox10, and enhances the thickness of the myelin sheath

The induction of myelin gene expression and consequent formation of myelin sheaths by SCs in vitro is dependent on the presence of L-ascorbic acid (vitamin C)

schwann cells need vitamin C to do their thing
so daily vitamin C also Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation

In this one below they just used the highest dose of the previous study. instead they found lithium, in cell study, prevented new myelation , but helped preserve & strengthen existing myelation. but the dose used was too high for humans

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459683/

Lithium preserves the integrity of pre-existing myelinated fibers.
Our combined data derived from isolated and axon-related SCs indicated that lithium blocks myelination by halting the onset of differentiation while preserving [& improving] the integrity of pre-existing myelin sheaths.
LiCl moderately enhanced O1 and MBP expression throughout the culture area

Because the doses of lithium herein used cannot be used in clinical therapy, we anticipate the need for further research in order to better assess the potential for translation.

Net effect in animals is motor neuron growth
and enhanced remyelination , by 6 weeks
https://pubmed.ncbi.nlm.nih.gov/27185485/
https://www.researchgate.net/figure...nerated-axons-in-the-MC-nerves_fig5_303095722
https://www.researchgate.net/figure...-accelerates-axon-regeneration_fig3_303095722
they used ~1gram human dose of lithium chloride
Lithium orotate is more potent , so might work in milligrams instead, but i dont know the conversion

Bromelain may be worth a look into also
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944371/
It helped nerve regeneration
around 500mg human dose. by 21 days
and as a bonus it inhibits neutrophil migration (may lower inflammation in the brain?)

CCI induced axonal degeneration of the sciatic nerve (Fig. 6C). This was manifested by an increased occurrence of swollen, proliferated myelinated and non-myelinated neurons (Fig. 6C). There was a significant reduction in the number of Schwann’s cells observed compared with the normal control group.
Bromelain administration mitigated these observed features (Fig. 6E, F). There were increases in the number of myelinated neurons and the numbers of swollen myelinated and non-myelinated neurons were grossly abated in the group treated with bromelain. The sciatic nerve of the pretreated bromelain group (Fig. 6G, H) showed nearly fully recovered structural integrity similar to the unligated control group.

Bromelain improved the sciatic nerve function in the ligated animals. Increased sciatic function has been linked with improvement in peripheral nerve regeneration and correlated with indices of muscular strength, as well as the electrophysiology and morphology of the peripheral nerves

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increasing BDNF may or may not be great for ALS - mixed studies whether its good or bad
tipping the balance with things too much can have opposite effects
too much BDNF can cause excitotoxicity through glutamate

potentiating BDNF has been one of the strategies to delay the disease progression of ALS. The modulation of TrkB via small molecule drug formulations to enhance BDNF signaling also enhanced neuronal survival in degenerating neurons in vitro (Guerzoni et al., 2017) and improved motor function and motor neuron loss in ALS model mice (Korkmaz et al., 2014).

BDNF potentiation has also been demonstrated to enhance MN survival in vitro (Tsai et al., 2013) and in other neurodegenerative diseases (Aytan et al., 2018). Additionally, transactivating TrkB by A2a receptors has also been reported to enhance survival of MNs in culture (Komaki et al., 2012). However, despite these neuroprotective effects observed there is also evidence to show that therapeutic interventions aimed at enhancing BDNF/TrkB are unable to promote survival or prevent death of neurons in vivo (The BDNF Study Group Phase III, 1999; Silani et al., 2001; Pansarasa et al., 2018).

This suggests that the detrimental actions of BDNF also need to be considered. Under certain circumstances, many studies report that BDNF/TrkB can exert negative effects on MN survival, making MNs more vulnerable to insults (Hu and Kalb, 2003; Mojsilovic-Petrovic et al., 2006). Moreover, BDNF is potent at enhancing excitotoxic insult, by enhancing glutamatergic activity in neurons (Kafitz et al., 1999).
Several studies report BDNF and TrkB to be key players in rendering MNs vulnerable to excitotoxic insult (Fryer et al., 2000; Hu and Kalb, 2003; Mojsilovic-Petrovic et al., 2005). Additionally, muscle from ALS patients expresses elevated levels of BDNF, suggesting the possible negative action of BDNF (Kust et al., 2002). Furthermore, BDNF can accelerate glutamate-induced death in rat neuroblastoma cells, and this effect was promoted by TrkB activation (Maki et al., 2015). BDNF also elicited glutamate excitotoxicity in cultured cortical neurons (Koh et al., 1995; Kim et al., 2003), and TrkB inhibition ameliorated these detrimental effects of BDNF (Kim et al., 2003).

It has also been shown that in vivo conditional deletion of TrkB in MNs of adult transgenic mice carrying a G85R SOD1 mutation attenuates SOD1 toxicity, resulting in extension of life span and motor function, slowing MN loss and causing persistence of neuromuscular junctions (Zhai et al., 2011).
Furthermore, in a recent study utilizing SOD1G93A rats, phrenic motor neurons displayed an increased expression of BDNF and phosphorylated ERK at end stage disease, consistent with possibly increased BDNF function and basal protein levels (Nichols et al., 2017).

Certainly, therapies that enhance endogenous BDNF have failed to produce any success in prevention or slowing of MN death in ALS. It is important to further investigate both pro- and anti-trophic functions of BDNF/TrkB in the hope of discovering novel therapeutic avenues to alleviate this devastating disease and other neurodegenerative conditions.

So it may not be a good idea to increase .
its confusing because the in vivo study of 7,8 DHF worked in animals , which mimics BDNF . and counters h2o2 also

7,8-Dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an enigmatic neurodegenerative disorder without any effective treatment characterized by loss of motor neurons …

www.sciencedirect.com

so maybe it comes down to individual levels tipped under or over. or late stage is not appropriate vs earlier stage?
maybe a way to tell don't need more BDNF is if have repeated continuous restlessness high mental activity seizures etc , from the glutamate. idk tho
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some targets
. help repair myelin / schwann cells & oligodendrocytes
[schwann cells are like oligodendrocytes but in the CNS , instead of brain]
. reducing neuroinflammation
[possibly through things that reduce neutrophil migration / chemotaxis as conditions like ALS = more neutrophils. & targetting h2o2 overload]
Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis

the ratio of neutrophils to CD16− monocytes (N:M ratio) is significantly increased in patients with ALS and better correlates with disease progression than any other single metric.

. helping mitochondria repair

 

[joaquin]

Magda Havas showed where a patient with MS started digressing when she bought a new plasma tv. Once the plasma TV was removed, the patient improved.