Blood-brain barrier permeability and physical exercise

Abstract

In this narrative review, a theoretical framework on the crosstalk between physical exercise and blood-brain barrier (BBB) permeability is presented. We discuss the influence of physical activity on the factors affecting BBB permeability such as systemic inflammation, the brain renin-angiotensin and noradrenergic systems, central autonomic function and the kynurenine pathway. The positive role of exercise in multiple sclerosis and Alzheimer’s disease is described. Finally, the potential role of conditioning as well as the effect of exercise on BBB tight junctions is outlined. There is a body of evidence that regular physical exercise diminishes BBB permeability as it reinforces antioxidative capacity, reduces oxidative stress and has anti-inflammatory effects. It improves endothelial function and might increase the density of brain capillaries. Thus, physical training can be emphasised as a component of prevention programs developed for patients to minimise the risk of the onset of neuroinflammatory diseases as well as an augmentation of existing treatment. Unfortunately, despite a sound theoretical background, it remains unclear as to whether exercise training is effective in modulating BBB permeability in several specific diseases. Further research is needed as the impact of exercise is yet to be fully elucidated.

The blood–brain barrier in health and disease: Important unanswered questions

“…However, whether neural activity dynamically regulates specific properties of the BBB to modulate circuit function remains unknown. While exercise might help to protect against BBB dysfunction in aging or disease, solid evidence is still forthcoming (Małkiewicz et al, 2019). A high-fat diet can increase BBB permeability (de Aquino et al, 2019; Salameh et al, 2019; Yamamoto et al, 2019), but the specific BBB properties affected have not been thoroughly characterized.…”

The Presence of Caffeic Acid in Cerebrospinal Fluid: Evidence That Dietary Polyphenols Can Cross the Blood-Brain Barrier in Humans

“…On the other hand, 4 patients with mononeuropathy or polyneuropathy without coexisting diabetes mellitus and any pathology localized in the brain represented detectable CA in CSF. Systemic inflammation negatively affects BBB function [58]. The majority of studied patients (especially those with MS) had plasma CRP, a marker of intensity of inflammatory response within normal range.…”

“…Although exclusion criteria involved diseases (stroke, head trauma, acute liver failure, hypertensive encephalopathy, HIV infection) that destroy the integrity and function of BBB [58,59], other diseases that were an indication for lumbar puncture and CSF collection may also enhance BBB permeability. For instance, MS and diabetes mellitus were reported to increase BBB permeability [58]. Moreover, two patients suffered from meningitis and one from brain tumor, diseases which potentially induce BBB dysfunction.…”

Immune System Modulations by Products of the Gut Microbiota

“…Similar effects were seen on the permeability of the blood–testis-barrier (BTB) in germ-free mice, after exposure to the bacteria Clostridium tyrobutylicum , which produces large amounts of butyrate [ 31 ]. Increased permeability at the BBB and BTB results in augmented infiltration of inflammatory molecules and immune cells to the brain and testis, often found in patients suffering from neurological diseases like multiple sclerosis or Alzheimer’s [ 32 , 33 ].…”