Leaky Brains Controlled by Microglial Response

In medicine, scientists search for targets which can be manipulated for health benefits.  The complexity of our systems makes such targets few and far in between.  Still they hope to discern the key players in disease processes like neurodegeneration.  For diseases like Alzheimer’s or Parkinson’s, they have learned that inflammation and a leaky blood brain barrier (BBB) intersect to increase risk of these and other neurodegenerative diseases.  As inflammation builds in our bodies, the BBB either protects the brain from damage or opens the door for ill health.

In this study, researchers used fluorescently labeled molecules and cells to discern the microscopy mechanisms underlying control of the BBB.  From a multitude of other studies, they knew that many neurologic and psychiatric diseases were related to increases in brain inflammation and decreases in the BBB.  They also knew that these inflammatory processes and the leakiness of the BBB interacted to produce such diseases.  Given that the microglial cells served as immune sentinels and sergeants in the brain, they explored what role these cells may play in the leaky BBB of patients with these diseases.

Using a mouse model, they determined that the microglia (brain immune cells) migrated to the BBB in the initial stages of inflammation.  Their presence initially lowered the BBB permeability, prevented the various cells making up the BBB (like astrocytes) from opening up too much.  This was a good thing for short term limitation of BBB leakiness.  However, when inflammation continued, these microglia appeared to increase the leakiness of the BBB.

Various chemical mediators were also determined to play roles in this process.  If researchers can discern how these cells and their chemical messengers interact in responding to inflammation, they hope to identify ways to modify this process and prevent disease.  One of the molecules they are investigating is minocycline, an antibiotic often used for acne.  This antibiotic reduces the leakiness of the BBB in mouse models of some brain diseases.  Understanding how to lower the leakiness of the BBB may allow clinicians to lessen the effects of both inflammatory brain diseases like Alzheimer’s and secondary inflammation from diseases like stroke.

Further research must continue in order to discern the most critical opportunities for intervention, but we do have some areas for therapy to begin in our functional medicine offices today.  Functional MD’s like myself know that inflammation plays a key role in many brain diseases.  We can turn down the inflammatory “heat” in our patients’ bodies by encouraging low inflammatory diets which avoid processed foods and high amounts of sugar.  We can augment our body’s God designed anti-inflammatory mechanisms with encouraging high nutrient/anti-oxidant diets.  We can identify and remove toxic and infectious triggers for inflammation like mercury or chronic Lyme disease.

While we don’t discount the benefits of medical research looking for the next pharmaceutical miracle, we also don’t ignore the simple and natural options for leading our patients to healthier more abundant lives now.  We strive to discern what each of our patients need and apply the best of natural and conventional therapies daily, advancing as science offers new insights like those above.



Original Article:

Koichiro Haruwaka, Ako Ikegami, Yoshihisa Tachibana, Nobuhiko Ohno, Hiroyuki Konishi, Akari Hashimoto, Mami Matsumoto, Daisuke Kato, Riho Ono, Hiroshi Kiyama, Andrew J. Moorhouse, Junichi Nabekura, Hiroaki Wake. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-13812-z


Thanks to Science Daily:

Nagoya University. “Two sides of a coin: Our own immune cells damage the integrity of the blood-brain barrier.” ScienceDaily. ScienceDaily, 28 February 2020. <www.sciencedaily.com/releases/2020/02/200228102209.htm>.


Other Articles of Interest

Links between inflammation and Brain Health:

D’Mello, C. & Swain, M. G. Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders. Brain. Behav. Immun. 35, 9–20 (2014).

Yirmiya, R. & Goshen, I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain. Behav. Immun. 25, 181–213 (2011).

Annane, D. & Sharshar, T. Cognitive decline after sepsis. Lancet Respir. Med. 3, 61–69 (2015).

Dumitrescu, A. L. Depression and inflammatory periodontal disease considerations-an interdisciplinary approach. Front. Psychol. 7, 347 (2016).

Barnes, D. E. & Yaffe, K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 10, 819–828 (2011).

Wyss-Coray, T. & Mucke, L. Inflammation in neurodegenerative disease—a double-edged sword. Neuron 35, 419–432 (2002).

Blood Brain Barrier and Brain Health:

Obermeier, B., Daneman, R. & Ransohoff, R. M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 19, 1584–1596 (2013).

Morris, G. et al. Leaky brain in neurological and psychiatric disorders: drivers and consequences. Aust. N.Z. J. Psychiatry 52, 924–948 (2018).

Microglial role in learning and development:
Parkhurst, C. N. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596–1609 (2013).

Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691–705 (2012).

Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F. & Schmidt, M. H. H. Microglia-blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol. 131, 347–363 (2016).





Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.

About the Author :

Leave a Comment