Signaling Growth and Regeneration in Brain and Body

Micro needling the skin to a depth of 0.5 mm improves regeneration of skin and reduced aging of skin to a depth of 12 mm due to signalling and increasing growth and regenerative peptides.

Knees undergoing sham arthroscopy improved equal to "clean out" procedures.

Knee synvisc injections divided into 5 shots were better than 3 shots were better than 1 shot.

Red Near infrared laser light improved joint pain by signalling growth and regeneration.

Red Near infrared laser light treatment of leg bone marrow activated adult mesenchymal stem cells to travel and relocated to injured brain where they attracted growth and regenerative peptides including BDNF.

The concept is clear that growth and regenerative peptides can be increased and work through a variety of signaling mechanisms.

One should not have to needle the hippocampus to signal.  Transcranial direct current, transcranial magnetic stimulation, red near infrared light stimulation or deep brain electrical stimulators would probably all work!

http://www.kurzweilai.net/micro-needle-insertion-into-hippocampus-helps-brain-regeneration-in-animal-model-of-ad

Urosolic Acid May Prevent Monocyte Activation and Prevent Inflammatory Diseases

Ursolic acid is derived from Apple skins.  50 mgs per medium sized Apple.  Also available as a supplement.

This article below shows that urosolic acid prevents "monocyte activation." Monocyte activation mobilizes glial cells to home in on cytokine releasing cells that are damaged in some way such as ischemia reperfusion which results in pyroptosis (inflamed cells) and apoptosis (death of cells) of the cells.  In effect collateral damage is increased and recovery is thwarted for damaged cells.  Using other terms metabolically stunned cells are programmed to die by releasing cytokines and activating glial cells.  Blocking cytokine derived death would prevent cell death and promote cell survival and recovery.

 If this is true for all monocyte cells including Microglial cells in brain, Kupffer cells in liver and Muller cells in the retina, it might prevent the following:

bipolar inflammation and symptoms, 

systemic sclerosis inflammation and symptoms, 

Alzheimer's inflammation and symptoms, 

nonalcoholic liver disease and symptoms, 

Parkinson's inflammation and symptoms, 

atherosclerosis inflammation and symptoms

Acute kidney injury inflammation and symptoms

Macular degeneration and vision loss.

Antioxidant action of most antioxidants has been measurably active mostly against ROS or reactive oxygen species. Reactive nitrogen species RNS antioxidant activity should also be reduced after metabolic stress such as ischemia reperfusion  stress.

Is urosolic acid a unique buffer of RNS directly or indirectly as an exercise and calorie restriction mimetic?  I suspect that the action is indirect or epigenic as it activates Sirtuin pathways in the same way as calorie restriction or exercise, both indirect epigenic modifiers of antioxidant pathway.

 Reservatrol, another antioxidant derived from the skin of grapes,  is an exercise and calorie restriction mimetic.  These plant skin products likely evolved to protect seeds and plants from harsh UVA and UVB damage of nuclear and mitochondrial dna.  It is logical that they would also affect mammalian cells with similar protection.  In effect, plants cannot exercise or voluntarily avoid calories from sunlight, therefore they would require their exercise and calorie restriction mimetics be derived from the energy produced from their genes.  If that is true, plants at the equator or desert (without shade) would likely have greater levels of these mimetics.

Ironically, a stress like exercise or calorie restriction induces a stronger antioxidant capability in mammals.

Exercise is a potent antioxidant.

Highlights

• •
  Ursolic acid protects monocytes from metabolic stress-induced dysfunction or “metabolic priming” by preventing the induction of Nox4.
• •
  Ursolic acid restores p38 MAP kinases activation and chemotactic responses to MCP-1 in monocytes exposed to metabolic stress.
• •
  Ursolic acid prevents increased protein S-glutathionylation, including actin-S-glutathionylation, in metabolically stressed monocytes.
• •
  Ursolic acid prevents MKP-1 degradation and restores MKP-1 activity in metabolically stressed monocytes.

http://www.sciencedirect.com/science/article/pii/S2213231714000184

Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4 ☆

Build a Better Network, Build a Better Teen?

The heritage and lessons of hard physical work is not easily available to teens today.  Think we need a proxy?
As I think about wilderness adventures, boot camps, team sport and education camps perhaps there is a wage based expenses required experience to allow coming of age to mean something.
Philmont, scouts, sports camps, sports, and summer jobs were significant for me.  Church camp not so much.  Ironically the physical and social quest of the former engendered more spiritual assets for me than the chapel of church camp.  The former was real and the second felt virtual.  Isn't it ironic that emphasizing the physical and social leads to the spiritual.
Similarly, cleaning bricks and building a retaining wall during our church building program engendered more tangible spiritual assets for me.  How much of spiritual growth is physical? Struggle? Doubt?
Faith exist beyond the mind and heart and physical and social portals have less barriers to strong imputs of character building works.
My current science insight is that lifestyles that increase BDNF brain derived neurotrophic factor and HRV heart rate variability index builds the network of mind and body to appreciate better the creator who designed us all to fast, pray work, learn and share hospitality in order to grow mentally, physically and spiritually.

I thought you would be interested in the following story from The Wall Street Journal.

Lessons From the Ranch: Schooling a Teen in Hard Work

http://www.wsj.com/articles/lessons-from-the-ranch-schooling-a-teen-in-hard-work-1459899578
Download the Wall Street Journal app here: WSJ.

Cellular Metabolic Health for Improved Brain and Heart Function Increases HRV

BDNF is a logical bio marker of cognitive impairment.

Should it also be a bio marker of heart failure from diastolic to systolic?

Below is the story of linkage or concurrent dysfunction (or function.)

The linkage is metabolic and inflammatory!

High function requires 1. BDNF associated high metabolic cellular health of target tissues and 2. control of inflammatory pathways of the innate and systemic immune systems.

Therefore the bio marker of metabolic health ( increased BDNF) and the bio marker of innate inflammation (increased NLRP3 and Caspase) are inversely proportional to healthy or unhealthy.

Heathy. Increased BDNF decreased NLRP3 and Caspase.

Unhealthy. Decreased BDNF, Increased NLRP3 and Caspase?

HRV is an index of BDNF and NLRP3/Caspase effects

Healthy is increased HRV. (Heart rate variability index)

Unhealthy is decreased HRV.

Therefore there are two strategic aims in treating both cognitive impairment and heart failure.

1. Increase BDNF.

2. Decrease NLRP3 and Caspase.

Did you know that ACE ARBs (that cross the blood brain barrier) 1. Reduce dementia or cognitive impairment by 65%?

Did you know that ACE ARBs reduce cardiovascular mortality by 7% and all cause mortality by 10%?

Did you know that ACE ARBs bind NLRP3 and prevent activation of the innate immune system?

Did you know that ACE ARBs reduce diabetic renal dysfunction or renal failure?

Did you know that ACE ARB treated hypertensive patients had a 9% reduction in diabetes in the treated group?

That DHA 1000 mgs reduces cognitive impairment, heart morbidity, and Caspase preactivation?

That high intensity interval exercise increases BDNF and reduces cognitive impairment and improves cardiac performance.?

That weekly 24 hour fasting in a mouse model of age related cardiomyopathy raised BDNF and restored normal EF after 8 weeks of intermittent fasting.

The EF or ejection fraction at rest and exercising is a global cardiac function test of systolic and diastolic dysfunction respectfully.

Is the mini mental status exam the corresponding EF of the brain? (Executive Function)

Is HRV the global function test of both systems because it measures the addition of BDNF and the subtraction of the innate immune system?

Ischemia in stroke and heart failure leads to ischemia repercussion injury; an index of metabolic and inflammatory dysfunction.  Classically it is seen as only oxygen deprived instead of oxygen and energy substrate pathway deprived pathophysiology.

http://link.springer.com/article/10.1007/s11936-015-0425-7

Management of Cognitive Impairment in Heart Failure

Joseph Thomas (Tony) Liverman, Jr.