Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 493 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:http://oc1dean.blogspot.com/2010/11/my-background-story_8.html

Friday, August 5, 2016

Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology

How much caffeine is your doctor prescribing? Or is your doctor doing NOTHING about your chances of getting dementia/Alzheimers? Don't do caffeine on your own, you know how dangerous drinking and eating is without a doctors prescription. And you don't know the quantities needed.
1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.
2. Then this study came out and seems to have a range from 17-66%. December 2013.
3. A 20% chance in this research.   July 2013.

Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology

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Figures
Fig. 1
Concentrations of caffeine and its metabolites in plasma and brains of chronically-treated animals. (A) Plasma and brain concentrations of caffeine and its metabolites (paraxanthine, theobromine, and theophylline) assessed using LC/MS. Caffeine is the main component found in the brain. (B) Brain:plasma ratio calculated from data given in (A) ratio is close to 1 for caffeine and is significantly lower for metabolites. Results are expressed as means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001 versus caffeine using 1W-ANOVA followed by a post hoc Fisher LSD test, n = 11/group. Results are given as average of pooled data from WT and Tau transgenic mice. Abbreviations: ANOVA, analysis of variance; LSD, least significant difference; SEM, standard error of the mean; WT, wild type.
Fig. 2
Caffeine prevents development of spatial memory impairments in THY-Tau22 mice. (A) Learning phase of the Morris Water Maze task. No difference is observed between groups during the learning phase using path length calculations following 2-way ANOVA. (B) Velocity is not modified regardless of groups following 1-way ANOVA followed by a post hoc Fisher LSD test. (C) Probe test performed 72 hours after the last day of learning. Results are expressed as means ± SEM of the averaged percent of total time spent in target quadrant (T) versus nontarget quadrants (NT). Data demonstrate that WT animals exhibit a significantly preference for target quadrant while THY-Tau22 mice treated with water did not. THY-Tau22 mice treated with caffeine significantly exhibit a preference for target quadrant as observed for WT animals. Results are expressed as means ± SEM. ** p < 0.01 versus Target, using Student t test; # p < 0.05 versus WT H2O using 1 way-ANOVA, n = 10–15/group. Abbreviations: ANOVA, analysis of variance; LSD, least significant difference; SEM, standard error of the mean; WT, wild type.
Fig. 3
Caffeine reduces tau phosphorylation and tau fragments in THY-Tau22 mice. (A) Western blot analysis of tau phosphorylation in THY-Tau22 mice treated with water or caffeine using antibodies targeting physiological (pSer214, pSer396, pSer404) and pathologic (pThr212/Ser214, pSer422) tau epitopes. We observe a significant decrease of phosphorylation of Thr212/Ser214, Ser396, and Ser422 epitopes as well as an increase of dephosphorylated tau using Tau1 antibody. Moreover, caffeine reduces tau fragments (f-Cter and f-Nter) concomitantly with an increased total tau levels (Cter and Nter). (B) Quantifications were performed over total tau levels (Cter). Total tau levels were quantified versus GAPDH, used as loading control. Results are expressed as means ± SEM. THY-Tau22 H2O versus THY-Tau22 caffeine: * p < 0.05, ** p < 0.01 using Student t test, n = 5–7/group. Abbreviation: SEM, standard error of the mean.
Fig. 4
Impact of caffeine on hippocampal tau kinases and PP2AC. Western blot analysis was performed using antibodies raised against total and/or phosphorylated forms of several tau kinases and PP2AC. Results indicate increased pErk and cdk5 in caffeine-treated animals together with an upregulation of PP2AC. Phospho-epitopes were quantified versus total form of respective protein. Total expressions were quantified versus GAPDH. Results are expressed as means percentage ± SEM of untreated animals. * p < 0.05, ** p < 0.01 versus nontreated animals, using Student t test, n = 5–7/group. Abbreviation: SEM, standard error of the mean.
Fig. 5
Caffeine modulates hippocampal neuroinflammation and oxidative stress markers in THY-Tau22 mice. qPCR analysis of hippocampal neuroinflammatory and oxidative stress markers. CD68, CD45, and TLR2 are innate immunity markers, GFAP is a marker for astrocytes; CCL4, CCL5, and TNFα are cytokines. Nrf2 is a transcription factor involved in the brain's antioxidant response. MnSOD catalyzes dismutation of superoxide anion and EAAT3 is a neuronal cysteine transporter important for de novo glutathione synthesis. All markers display increased levels in water-treated THY-Tau22 mice compared with WT animals. Caffeine treatment significantly reduced levels of CD45, TLR2, CCL4, TNFα, Nrf2, MnSOD, and EAAT3 in THY-Tau22 mice. Results are expressed as means ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001 versus WT H2O; # p < 0.05, ## p < 0.01, ### p < 0.001 versus THY-Tau22 H2O using 1 way-ANOVA followed by a post hoc Fisher LSD test, n = 6–10/group. Abbreviations: ANOVA, analysis of variance; LSD, least significant difference; qPCR, quantitative polymerase chain reaction; SEM, standard error of the mean.

Abstract

Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients.

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