The therapeutic potential of early exercise in Alzheimer's disease: Focus on the brain-spleen axis

 Now your competent? doctor needs to get you recovered enough to do this exercise and hopefully prevent Alzheimers.

DOES YOUR DOCTOR HAVE EXACT DEMENTIA PREVENTION PROTOCOLS? NO? So, your doctor is incompetent? 

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.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here: 

The therapeutic potential of early exercise in Alzheimer's disease: Focus on the brain-spleen axis

Author links open overlay panel, , 

https://doi.org/10.1016/j.arr.2025.102980Get rights and content

Highlights

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  Brain-peripheral immune crosstalk is evident in Alzheimer's disease (AD).
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  Splenic immune dysfunction exacerbates AD via brain-peripheral immune crosstalk.
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  The brain-spleen axis represents a critical pathway that regulates splenic immunity.
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  Extensive neurodegeneration in AD impairs the brain-spleen axis.
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  Early exercise may slow AD progression by modulating splenic immunity via the brain-spleen axis.

Abstract

Alzheimer's disease (AD) is the predominant cause of cognitive dysfunction, with global prevalence increasing annually. AD progression is principally driven by the accumulation of amyloid-β (Aβ) and hyperphosphorylated microtubule-associated protein tau (p-Tau), which trigger a subsequent cascade of neuroinflammatory responses within the central nervous system (CNS). This pathological cascade is regulated by reciprocal CNS-peripheral immune crosstalk. The brain-spleen axis has emerged as a critical conduit that orchestrates splenic immune activity and CNS-peripheral immune crosstalk during AD progression. Notably, through the brain-spleen axis, early-life and preclinical exercise may restore splenic vagal-sympathetic homeostasis, re-establish immune equilibrium, and then mitigate neuroinflammation. This review advances a testable hypothesis that early exercise prevents or attenuates AD pathology through the brain-spleen axis, potentially accelerating the development of innovative therapeutic targets such as non-invasive brain stimulation.

Abstract WP95: Splenectomy Protects Aged Mice From Cerebral Injury in the Experimental Stroke Model

What the hell made you think that spleen removal would help in stroke? You thought there was any chance in hell that this could be tried in humans? Was this problem considered?

Splenectomy Does Not Improve Long-Term Outcome After Stroke  Jan. 2017

Abstract WP95: Splenectomy Protects Aged Mice From Cerebral Injury in the Experimental Stroke Model 

Anjali Chauhan, Meaghan Roy-O’Reilly, Abdullah Mamun, Nia Harris, Javiera Bravo-Alegria, Louise McCullough

Stroke. 2017;48:AWP95

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Abstract

Introduction: Aging is a non-modifiable risk factor for stroke. Although aged animals tend to have smaller infarcts they have worse functional recovery after stroke, suggesting difference in mechanisms between young and aged. Splenectomy reduces infarct in animal models, but how the spleen contributes to brain injury in aged mice has not been as well studied.

Hypothesis: We hypothesized that peripheral inflammation increases over the lifespan. We predicted that the detrimental effects of the spleen would be reversed by splenectomy in aged mice.

Methods: Young and aged male mice were splenectomized (n= 8-9), 2 weeks prior to induction of 1 hour of middle cerebral artery occlusion. Ninety-six hours after reperfusion, behavioral and infarct area was assessed. In a separate cohort, peripheral and central immune cells were quantified by flow cytometry.

Results: After stroke, there was 13.3, 17.7, 25.9 and 5.88% mortality in spleen intact young, splenecyomized young, spleen intact aged and splenctomized aged mice respectively. Splenectomy led to improved behavioral deficits in aged mice as seen by lower neurological deficits scores,(1.63 ± 0.26 Vs 2.57 ± 0.20) and reduction in number of right turns in the corner test. There was significant reduction in infarct size in the splenectomized aged mice (p<0.05) as compared to spleen-intact mice. Splenectomy in aged mice lead to reduction in the frequency of CD3CD44+ T cells. Additionally, there was significant decrease in TNF-α, IL-6, IL-4, IL-12MIP-1b and RANTES levels in the aged splenectomized aged mice as compared to spleen-intact aged mice (p<0.05). In the brain, the frequency of CD45hiCD11b+ cells was reduced in the splenectomized MCAo aged as compared to spleen-intact stroke mice (p<0.05).

Conclusions: Splenectomy reduced the peripheral activation of T cells in the aged mice. Also less peripheral leukocyte infiltration was observed, which mirrored improved functional recovery and reduced infarct damage in splenectomized aged mice. Hence, this study provides new information regarding age specific peripheral immune responses and interaction with the brain after experimental stroke highlighting a need for the incorporation of aged mice in the basic stroke research. Funding: 16POST27490032

USF study shows spleen may be a new target for treating stroke-induced chronic inflammation

More research that will failed to be followed up by our failures of stroke associations. There must be tens of thousands of research studies not being followed up on since I started blogging 6 years ago.
http://www.news-medical.net/news/20150916/USF-study-shows-spleen-may-be-a-new-target-for-treating-stroke-induced-chronic-inflammation.aspx

Stroke injures the brain, but a new University of South Florida (USF) study indicates an abdominal organ that plays a vital role in immune function, the spleen, may be a target for treating stroke-induced chronic inflammation leading to further brain cell death.
Neuroscientists at the USF Center of Excellence for Aging and Brain Repair found that human bone marrow stem cells intravenously administered to post-stroke rats preferentially migrated to the spleen and reduced the inflammatory-plagued secondary cell death associated with stroke progression in the brain. The study is reported in the September 2015 issue of the American Heart Association journal Stroke.
The USF study helps resolve a perplexing observation by many scientists evaluating the effects of stem cell therapies: Functional recovery occurs in experimental models of neurological disorders, including stroke, despite little or mediocre survival of transplanted stem cells within the injured brain.
"Our findings suggest that even if stem cells do not enter the brain or survive there, as long as the transplanted cells survive in the spleen the anti-inflammatory effects they promote may be sufficient enough to therapeutically benefit the stroke brain," said principal investigator Cesario Borlongan, PhD, professor and director of the USF Center of Excellence for Aging and Brain Repair.
Stroke is a leading cause of death and the number one cause of chronic disability in the United States, yet treatment options are limited. Stem cell therapy has emerged as a potential treatment for ischemic stroke, but most preclinical studies have looked at the effects of stem cells transplanted during acute stroke - one hour to 3 days after stroke onset.
Following acute stroke, an initial brain attack caused by lack of blood flow, the blood-brain barrier is breeched, allowing the infiltration of inflammatory molecules that trigger secondary brain cell death in the weeks and months that follow. This acerbated inflammation is the hallmark of chronic stroke.
The USF researchers intravenously administered human bone marrow stem cells to rats 60 days following stroke onset - the chronic stage. The transplanted stem cells were attracted predominantly to the spleen; the researchers found 30-fold more stem cells survived in this peripheral organ than in the brain. Once in the spleen, the stem cells dampened an inflammatory signal (tumor necrosis factor) activated immediately after stroke and prevented the migration from spleen to the compromised brain of harmful macrophages that stimulate inflammation.

This reduced systemic inflammation correlated with significant decreases in the size of lesions caused by acute stroke in the striatum--a portion of the brain controlling movement. There was a trend toward prevention of additional neuron loss in the portion of the brain affecting memory and thinking.
"In the chronic stage of stroke, macrophages are like fuel to the fire of inflammation," Dr. Borlongan said. "So if we can find a way to effectively block the fuel with stem cells, then we may prevent the spread of damage in the brain and ameliorate the disabling symptoms many stroke patients live with."
The USF researchers next plan to test whether transplanting human bone marrow stem cells directly into the spleen will lead to behavioral recovery in post-stroke rats.
The one drug approved for emergency treatment of stroke, the clot-busting drug tPA, must be administered less than 4.5 hours after onset of ischemic stroke, and benefits only 3 to 4 percent of patients, Dr. Borlongan said. While more study is needed, evidence from USF and other groups thus far indicates stem cells may help provide a more effective treatment for stroke over a wider timeframe.
"Stem cells are not a magic bullet, but a combination of stem cells and other anti-inflammatory agents may lead to the optimal therapeutic benefit for stroke patients," he said.
Lead study author Sandra Acosta, PhD, a postdoctoral fellow in the USF Department of Neurosurgery and Brain Repair, said targeting the spleen with stem cells or the anti-inflammatory molecules they secrete offers hope for treating chronic neurodegenerative diseases like stroke at later stages.
"We've shown (in an animal model) that it's possible to stop disease progression 60 days after the initial stroke injury, when chronic inflammation in the brain was widespread," she said. "If that can be replicated in humans, it will be powerful."

Source:

University of South Florida (USF Health)

Changes in spleen size in patients with acute ischemic stroke: a pilot observational study

I couldn't figure out the connection at first.
http://onlinelibrary.wiley.com/doi/10.1111/ijs.12022/abstract;jsessionid=5BCB8F56E42B7F750C6E98F8AFEB6ABA.d03t03

Background

In animal models, the spleen contracts after acute ischemic stroke, followed by release of inflammatory cells leading to secondary brain injury.

Aims

We aim to characterize splenic responses in patients with acute ischemic stroke.

Methods

In this prospective observational study, we measured daily spleen sizes with abdominal ultrasound in 30 patients with suspected acute ischemic stroke. Splenic ultrasounds were also performed in 20 healthy individuals.

Results

A generalized estimating equation, longitudinal regression model for adjusted spleen measurements showed the difference between baseline spleen volume (within six-hours of stroke onset) and the volume at the last measured time point (up to seven-days) to be statistically significant (volume difference of 51·9 cm³, P =  0·04). Healthy controls had significantly smaller day-to-day variations; the maximum observed difference in mean spleen volume between any two time points was 9·5 cm³, with the average change over the period of observation being 1·24 cm³. A statistically significant negative association was also observed between the pattern of change of total white blood cell count and spleen volume (P = 0·01). An analysis of individual cases demonstrated possible associations between daily spleen volume changes and clinical course.

Conclusions

We hypothesize that the spleen may initially contract after ischemic stroke followed by a re-expansion and that it contributes to ischemic brain injury mediated via cellular components. Characterization of the splenic response after stroke and its contribution to cerebral ischemic injury has the potential to provide new opportunities for the development of novel stroke therapies.