u/barweis

Those amazing EVs - extracellular vesicles - are getting into a new scenario no longer in their native circulatory system. Question is whether they can function in a nasal spray to reverse brain fog in LC19 as they purport to do in another brain fog instance. Neurodegeneration shares many commonalities across the span of neuropathology. Nature is invariable in the very basic conduct of chemical reactions and other physical phenomena so one might expect similar activity in similar processes.

Now can we pull the Long Covid crews out of their silos to set up a course leading to an eventual trial on LC19 patients? I hope these pleas catch the eye of RECOVER dudes that are lagging several generations behind the dementia study folks to get in on the cutting edge of research.

Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus doi: 10.1002/jev2.70232 https://pmc.ncbi.nlm.nih.gov/articles/PMC12884020/

From the ABSTRACT:..."the hippocampus of animals receiving hiPSC-NSC-EVs exhibited reductions in astrocyte hypertrophy, microglial clusters, and oxidative stress, along with elevated expression of antioxidant proteins and genes that maintain mitochondrial respiratory chain integrity. Moreover, hiPSC-NSC-EVs therapy decreased the levels of various proteins involved in the activation of the NLRP3 inflammasome, p38/mitogen-activated protein kinase, cGAS-STING-IFN-1, and Janus kinase and signal transducer and activator of transcription signalling pathways."...

"3.2 Biodistribution of IN-Administered hiPSC-NSC-EVs in the Brain of Late Middle-Aged Mice The biodistribution of IN-administered PKH-26-labeled hiPSC- NSC-EVs was examined in multiple brain regions using markers of neural cells at 6 h post-administration (Figure 1E, F ) in both male and female mice. Such analysis revealed that hiPSC- NSC-EVs permeated virtually all brain regions within 6 h post-administration, as demonstrated in our earlier studies for naïve mice (Upadhya et al. 2020 ) and 5 × Familial AD (5 × FAD) mice (Attaluri et al. 2023 ). In all brain regions, EVs were taken up by microglia and neurons. EVs were also seen interacting with the cell membranes of astrocytes and oligodendrocytes."...

3.6 hiPSC-NSC-EVs Enhanced Mitochondrial Respiratory Chain Gene Expression in the Hippocampus

..." Thus, hiPSC-NSC-EVs treatment in late middle-aged male and female mice enhanced mitochondrial respiratory chain gene expression in the aged hippocampus. "

In plain terms the extracellular vesicles were introduced by the nose and distributed to and taken up by microglia and neurons and interacting with other "supporting cells" in the brain parenchyma. So they circulate in the entire brain. Mitochondrial support genes were activated.

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FYI: the press release for the study emanates from "Texas A&M University Division of Marketing and Communications" so you know their aim is to monetize it and reap profits from the captive public if it makes a hit. There aint no free lunch!

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"Scientists reverse brain aging, with a nasal spray New therapy is turning back the clock in aging brains, healing inflammation, restoring memory and reshaping the future of brain age-related therapies.

April 14, 2026 By Zaid Elayyan, Texas A&M University Division of Marketing and Communications ........................ The above presentation is a result of my speculations following the Alzheimer's literature and Long covid as well.

At present I recommend the web page at drugs.com for a comprehensive and detailed listing of over (700) seven hundred known interactions that either raise or lower lithium levels when taken within a close time frame. This is due to the varying metabolism of individual drugs as they are eliminated from the body. The nudge of a slight change can cause toxicity eventuating in variable timeframes due to persons habits, genetics, accompanying illnesses, diet, concomitant meds including herbs and supplements, alcohol and other 'recreational' substances, etc.

MAIN INTERACTION CHECKER:

https://www.drugs.com/drug-interactions/lithium.html

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References:

Clinical Pharmacokinetics, 6th Edition; Lithium, pp.328-348 American Society of Health-System Pharmacists

Normal levels of lithium – Can it still be harmful? (2019) doi: 10.4103/psychiatry.IndianJPsychiatry_274_18 https://pmc.ncbi.nlm.nih.gov/articles/PMC6657541/

Drug-induced lithium toxicity in the elderly: a population-based study DOI: 10.1111/j.1532-5415.2004.52221.x https://pubmed.ncbi.nlm.nih.gov/15086664/

Drug‐drug interactions as a determinant of elevated lithium serum levels in daily clinical practice doi: 10.1111/j.1399-5618.2005.00199.x. https://pubmed.ncbi.nlm.nih.gov/15898965/

Drug-Drug Interactions Between Lithium and Cardiovascular as Well as Anti-Inflammatory Drugs DOI: 10.1055/a-1157-9433 https://www.thieme-connect.com/products/ejournals/abstract/10.1055/a-1157-9433

Lithium therapy and its interactions doi: 10.18773/austprescr.2020.024 https://pmc.ncbi.nlm.nih.gov/articles/PMC7358048/

Lithium Toxicity https://emedicine.medscape.com/article/815523-overview#showall

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The Science and Practice of Lithium Therapy. p.129

"7.2.5 Lithium Blood Levels A fifth difficulty that should also be taken in account is the variability of lithium response due to its blood level. As lithium has a narrow therapeutic index, plasma lithium levels can be measured safely and accurately and are reasonable proxies for concentrations in the brain. Titration of plasma levels according to clinical need and symptomatic profile is a useful approach (Kleindienst et al. 2007 ), and this individualization of lithium dosage, on the basis of polarity, is likely to enhance efficacy and reduce side effects. Severus et al. ( 2009 ) has also shown that depression-prone bipolar disorder patients are likely to benefit from prophylactic lithium levels of 0.4–0.8 mmol⁄L, whereas those predisposed to mania tend to benefit from higher levels of 0.6–1.0 mmol⁄L. Thus, as mentioned by Malhi et al. ( 2011 ), lithium needs to be measured both literally in terms of its plasma levels and metaphorically, with respect to its clinical and functional effects."... (Additionally lithium levels should be drawn on the convention of a fixed time from the last dose with other parameters applying to the patient. Also noted are the variations of the lithium level in tissues of different compartments of the body. Clinical Pharmacokinetics, 6th Edition; Lithium, pp.308-312 American Society of Health-System Pharmacists)

Highlighted above in the excerpt are levels referring to the regular high dose regimen of the BPD patient. They do not correspond to the healthy or normal individual including LC19ers taking trace or micro doses.

Lastly:

"The saying, "A physician who treats himself has a fool for a patient," is a well known-Oslerism." Get yourself a medical doctor invested in LC19.

Two months late but came a round about way, sidetracked on other posts, to lithium and sleep. Here are article excerpts for common use outside of bipolar disorder, cluster and similar trigeminal headaches and Kleine-Levin syndrome. In LC19 with multisystem disorders including circadian rhythm sleep cycle disruption or endocrine induced, MCAS, ME-CFS, or 'vanilla' LC19 effects, restorative sleep is a necessity of the highest order to enhance mitochondrial repair and glymphatic drainage of waste products from the brain which could lower brain fog(Glymphatic Dysfunction: A Bridge Between Sleep Disturbance and Mood Disorders DOI: 10.3389/fpsyt.2021.658340 https://pubmed.ncbi.nlm.nih.gov/34025481/).

............................ Lithium Carbonate: Effects on Sleep Patterns 01 Normal and Depressed Subjects and Its Use In Sleep-Wake Pathology (1987) doi: 10.1055/s-2007-1017102. https://pubmed.ncbi.nlm.nih.gov/3313443/

"Abstract The effects of lithium carbonate on sleep patterns have been investigated both acutely in normal and depressed subjects and chronically in depressed subjects. In normal subjects receiving lithium for two weeks total sleep time did not vary, REM sleep decreased and REM sleep latency increased. In depressed subjects, either on short term therapy or on long term therapy stages 3 and 4 increased, REM sleep decreased, REM latency increased and REM activity/time spent asleep (an index of REM intensity per minute of sleep) decreased. Plasma lithium levels were negatively correlated with REM sleep percentage and positively correlated with REM sleep latency. Besides, it has been shown in one paper that short term therapy with lithium caused small but significant delays in the sleep-wake circadian rhythm."...

"Finally, there was a study by Bert et al. (1977) comparing the sleep patterns of normal subjects to the sleep patterns of these same subjects during the last three nights of lithium administration for 17 consecutive days. The sleep patterns of normal subjects were also compared to those of depressed subjects treated for an average of 22 consecutive months. In normal subjects the only recorded modifications were a reduction in REM sleep duration and an increase in REM sleep latency. There was no modification of stages 3 and 4. In depressed subjects the duration of stages 3 and 4 was increased, REM sleep duration was decreased, and REM latency was increased in comparison with the control subjects.

In conclusion, these studies showed a reduction in REM sleep, a decrease in REM activity and a lengthening of REM latency, the degree of which varied with the different studies. Stages 3 and 4 were increased in subjects with affective illness, but not in normal controls, who had normal levels for these stages before treatment. These modifications were not specific for one c1inical state, as the same sleep patterns could be found in nondepressed psychiatric patients as well as in depressed subjects." .................................

The Effect of Lithium Carbonate on the Circadian Rhythm of Sleep in Normal Human Subjects (1979) https://pubmed.ncbi.nlm.nih.gov/476235/

"DISCUSSION In contrast with the placebo condition, lithium appeared to cause small, but significant delays (14.2 min or 3.64") in the sleep-wake circadian rhythm of these subjects, and the sleep-wake phase delay appeared related to lithium's effect upon endogenous biological oscillators, since neither quality nor quantity of sleep and napping were affected. Since these data were derived from self reported questionnaires rather than from empirical observations, the results were subject to inadvertant errors of recall, and studies with objective recording are needed. However, our preliminary data are fully consistent with the prospective hypotheses.

Even though the phase shifts which we have observed are small, there have been studies indicating that shifts of this magnitude have profound effects. Elliott (1916) found that a change in the 24-hr light-dark cycle of only 36 min was sufficient to initiate gonadal development and testosterone output in golden hamsters.

The effects in human subjects of phase shifts of this nature are not fully known, particularly if such shifts are maintained over a long term as in therapeutic lithium treatment regimens. This is to our knowledge the first report of lithium's potential effect upon circadian rhythms in a sample of normal human subjects, and results are promising enough to warrant further investigation using a more traditional methodology for the study of biological rhythms in man." ................................ Effect of Strenuous Exercise on Serum Lithium Level in Man (1982) doi: 10.1176/ajp.139.12.1593. https://pubmed.ncbi.nlm.nih.gov/6816076/

..."Our finding that the sweat-to-serum ratios for lithium and potassium were about 3#{189}to 4 times greater than those for sodium and chloride are in keeping with ratios calculated from the data of Amatruda and Welt (9), which showed a potassium ratio 2-10 times greater than the sodium ratio.

Exercise-related shifts among body compartments of water, electrolytes, and lithium could also contribute to the variation in serum lithium level, especially because plasma volume appears to be maintained at the expense of intracellular volume during prolonged exercise (10). It is also possible that changes in intracellular lithium level do not parallel those in serum, and, conceivably, tissue lithium levels could remain unchanged or even increase." ..............................

Lithium: how low can you go? (2024) doi: 10.1186/s40345-024-00325-y https://pmc.ncbi.nlm.nih.gov/articles/PMC10828288/

"‘Micro’ dose [5-20 mg ionic lithium] 5-20  mg lithium (equivalent to 27-107  mg lithium carbonate) can be purchased over the counter as a nutritional supplement, most commonly in the form of lithium orotate (Strawbridge and Young 2022)."...[My comment: Lithium aspartate is also commonly available and does not have questionable nocive effects of the orotate]

..."Survey data from 211 people taking microdose lithium purchased commercially suggest that people commonly find benefits to mood, anxiety and cognition (each rated by > 20% of people) with mood commonly reported as the greatest benefit, most frequently ‘moderate’ in magnitude (Strawbridge 2023). While microdose lithium may have potential, we argue that initial feasibility and subsequent substantive examination in clinical trials are warranted."

"‘Trace’ dose [< 5 mg ionic lithium] Elemental lithium is naturally present in most rocks, meaning that trace levels are found in mineral water and food grown in soil. This varies substantially across region, with some mineral waters containing up to 9  mg/L (Schrauzer 2002). As a result, average dietary lithium intake has been estimated to increase to as much as 80  µg Li/kg-day (Moore 1995)"...

..."Better known in our field is the increasingly-documented association between higher trace elemental lithium intake from drinking water supplies and reduced suicide rates from ecological studies; this was meta-analysed from areas in Japan, Greece, USA, Austria, UK, Italy and Lithuania (Memon et al. 2020), with similar subsequent studies in Argentina (López Steinmetz et al. 2021), Hungary (Izsak et al. 2022) and Lithuania (Liaugaudaite et al. 2021). Similar, albeit less frequent and/or consistent, reports have been published related to reduced hospital admissions, dementia rates, depressive and anxiety symptoms and violent behaviour (Eyre-Watt et al. 2021) as well as all-cause mortality and premature death (Fajardo et al. 2018). While these findings have not yet been established as associated with confounding factors, most examinations are at a population-level and findings remain uncertain as to individual benefits. "...

Finally the article lists factors to be determined regarding different salts to deliver equivalent amounts, confounding factor of food intakes which affect absorption and the need for more insight into the long term effects of trace and micro dose delivery. ............................

Lithium increases slow wave sleep: possible mediation by brain 5-HT2 receptor (1989) DOI: 10.1007/BF00442020 https://pubmed.ncbi.nlm.nih.gov/2498958/

"Discussion Our study provides the first evidence, as far as we are aware, that lithium may increase SWS in normal subjects. There are previous reports that lithium increases SWS in depressed patients (Chernik et al. 1973; Kupfer et al. 1974), but in these studies it is difficult to separate the effect of lithium on SWS from that of clinical improvement. An earlier investigation in normal subjects found only a slight, non-significant, increase in SWS (Bert et al. 1977). Interestingly, the effect of lithium in decreasing REM sleep, which was detected in this study with automatic sleep stage analysis, has been reported in both depressed and normal subjects (Kupfer et al. 1974; Billiard 1987)."... .............................

See also: Effect of Lithium on Mood, Cognition, and Personality Function in Normal Subjects\DOI: 10.1001/archpsyc.1979.01780080034010 https://pubmed.ncbi.nlm.nih.gov/378164/ ..................................... .....................................

Hope you enjoy a long restful sleep after slogging through this soporific topic. Good night and pleasant dreams all if your REM phase prevails for a short duration!

Jeffries and Schumer definitely have to leave. Their functioning is unable to deal with the playbook of unpredictable sadistic opposition from MAGA. We need fresh thinkers raised in the midst of our chaotic changing political landscape. Their 100% record of failures landed us in the worst possible morass from which we may be able to extricate ourselves in a prolonged effort were they to remain at the helm of the Democratic party. Even Kamala Harris is unappealing to put into play. Their views are regressive and way out of line with meeting our demands to refashion a more aggressive appeal to disgruntled voters. Fire the bosses and get new blood aboard.

Reference:

Mitochondrial vulnerability underlies myocarditis from COVID-19 mRNA vaccine https://www.nature.com/articles/s41467-026-71295-1