and the comment on exercise, which I have discussed with a colleague working in experimental neuropathology, is quite intesting:
Exercise
Exercise is a promising mechanism of prevention and treatment for various diseases characterized by neuroinflammation.
[9] Aerobic exercise is used widely to reduce inflammation in the periphery. Exercise has been shown to decreases proliferation of
microglia in the brain, decrease
hippocampal expression of immune-related genes, and reduce expression of inflammatory cytokines such as
TNF-α.
Hello Charles
While regular sustained exercise may have value in protecting against the development of conditions such as Alzheimers, Huntington's etc characterised by neuroinflammation I suspect that some caution would be needed where neuroinflammation/microglial priming is already established.
I was digging around recently trying to identify a common 'signal' that might trigger PEM in response to diverse stressors such as physical and mental exertion and emotional stress. One strong candidate is the ubiquitous protein high mobility group box-1 (HMGB-1 or box-1 for convenience). Box-1 has been shown to be the proximal signal that primes and activates microglia in response to Danger-Associated Molecular Patterns (DAMPs) induced by cellular necrosis, infection, cellular/metabolic stress (advanced glycation end products) and strangely enough also psychological stress.
http://www.ncbi.nlm.nih.gov/pubmed/25568124
Exercise also actutely increases the expresssion of box-1 in parallel with the increase in cell free DNA :
"Immune-response patterns observed after acute bouts
of physical activity show similarities to those induced
by acute infection and trauma (1 ). Intense exercise has
recently been reported to provoke increases in the
plasma and serum concentrations of circulating cellfree
DNA (cf-DNA)3 (2, 3 ), a phenomenon considered
a hallmark of various pathologic conditions, including
cancer, autoimmune diseases, trauma, sepsis, stroke,
and myocardial infarction."
"In healthy individuals, excess cf-nDNA is rapidly
clearedfrom the circulation after the cessation of exercise.
Delayed or impaired clearance of cf-nDNA is especially
implicated in the disease pathogenesis of autoimmune
disorders, such as systemic lupus erythematosus (11 ),
and, remarkably, athletes who experience chronic fatigue
syndrome displayincreased seroprevalence of antinuclear
antibodies"
http://www.clinchem.org/content/57/4/633.full.pdf
Interestingly box-1 is termed a 'late inflammatory mediator' with peak levels somewhere between 48 and 72 hours after induction. If elevated by exercise then the peak would most likely be 'post-exertional'.
By way of analogy, post-concussion syndrome is a chronic multi-symptom, multi-system syndrome remarkably similar to ME/CFS (including exacerbated symptoms with exercise and alcohol intolerance) which affects only a small proportion of those with a 'mild traumatic brain injury'. The nice thing (sic) is that the initial trigger is unambiguously 'neuroinflammation'.
Because a high proportion of concussion cases are athletes there has been a great deal of attention paid to rehabilitation and getting ahtletes back to being able to tolerate exercise but until recently standard medical advice has been to avoid exercise altogether until completely asymptomatic yet some still go on to develop post-concussion syndrome.
One practitioner however has shown that early introduction of a graded exercise programme can aid recovery of exercise tolerance and reduce the proportion of those developing post-concussion syndrome. BUT unlike GET for ME/CFS the protocol is deliberately tailored to each individual with the intention that the exercise protocol totally avoids ANY exacerbation of symptoms which may be interpreted as keeping the activity at a level that promotes healing but below that at which primed microglia are activated.
Just some thoughts.
