The 20 Most-Read BrainImmune Stories of 2018

The 20 Most-Read BrainImmune Stories of 2018
The greatest gift is the gift of learning (Native American saying)

Over the past couple of years, each month we have posted the list of the top 10 most-viewed articles.

New for 2019, we introduce our first annual countdown for the 20 most-read articles on BrainImmune.

For 2018’s  annual list, the #1 most-read story is Walter Cannon: Homeostasis, the Fight-or-Flight Response, the Sympathoadrenal System, and the Wisdom of the Body. This article is authored by David S. Goldstein, M.D., Ph.D., a Senior Investigator at the National Institutes of Health (NIH), Bethesda, MD, USA. Dr. Goldstein is a recognized worldwide expert in physiology and neuroscience of the human autonomic nervous system, and an author of the Adrenaline and the Inner World: An Introduction to Scientific Integrative Medicine.

Walter CannonWalter Bradford Cannon, one of America’s leading physiologists, and former Chairman of the Department of Physiology at Harvard Medical School (1906-1942), invented the terms and developed the concepts of ‘homeostasis’ (stability of the inner world);  the ‘Fight or Flight Response’, and The ‘Sympathoadrenal System’. In 1932, Cannon published The Wisdom of the Body, where he popularized the new term of the dynamic equilibrium/steady state of the internal milieu or homeostasis.

We believe that Goldstein’s article about Walter Cannon, in contrast to other sources available online, provides an extensive and comprehensive description and analysis of the nature of these concepts and how these three theories were developed in the first half of the 20th century. Of note, as per David Goldstein, Cannon’s notion of a unitary sympathoadrenal system endures to this day. Many situations, however, entail differential regulation of the sympathetic nervous system and adrenomedullary hormonal system.

Coming in at #2, somewhat surprisingly to us, is The Evolving Link between Social Media Addiction and Depression in Young Adults. At first glance, there is no a direct connection between social media overuse and health risks or neuroendocrine-immune dysfunction. But despite the recent message from the UK Royal College of Pediatrics that there is “no good evidence that time in front of a screen is ‘toxic’ to health, the articleDigital Media, Anxiety, and Depression in Children’ discussed in the above-mentioned social media seems to suggest the opposite. This article was published in Pediatrics, the official journal of The American Academy of Pediatrics.

Major depression is a common but serious mood disorder, where both neuroendocrine and immune dysfunctions play a major role. It is also known that major depression contributes to serious health hazards such as the development of cardiovascular diseases. Thus, the social media overuse, may in fact be linked to health risks and a neuroendocrine-immune dysfunction.

Our 3rd most-read story on the annual 2018 list is The Discovery of Adrenaline. This article is written by Profs. Ashley Grossman and David Jessop, two leading neuroendocrinologists and neuroscientists in the UK. The popularity of this fascinating story may suggest a high readership interest about the history and physiology of adrenaline (also known as epinephrine), a major stress hormone, and major player in regulation of homeostasis and the sympathoadrenal system (see above).

Interestingly, in our top 20 list, 4  articles are related to some historical perspectives of neurosciences and immunology:

Claude Bernard, the Father of Modern Physiology and Experimental Medicine (#5), written by Prof. Vincent Geenen, is in fact very much related to the Walter Cannon’s story mentioned above. In 1865, Bernard published his famous book ‘Introduction to the Study of Experimental Medicine, where he established the general principles of experimentation in physiology and medicine. Alexis Carel said of Bernard: “Before him, medicine was purely empirical. He is responsible for the introduction of the scientific method in the art of healing”. Two of the most famous passages and quotes in the history of physiology belong to Bernard, “The constancy of the internal environment is the condition for free and independent life…All the vital mechanisms, however varied they might be, always have one purpose, that of maintaining the integrity of the conditions of life within the internal environment.” Cannon invented the word homeostasis, but the concept of homeostasis was a direct extension from Bernard’s of the milieu intérieur.

Bartolomeo Eustachius and the Discovery of Adrenal Glands (#13) is directly connected to stress and the peripheral stress system, as the adrenals secrete the two major stress hormones, adrenaline and cortisol.

Hans Selye stressHans Selye and the Birth of the Stress Concept (#9) provides a fascinating story about the investigator who introduced in medicine the widely used and popular term ‘stress’, and how this concept evolved in the 1930s and 1940s. More information about Hans Selye is available at Hans Selye and the 80th Birthday of Stress Research and Stress: From Hans Selye to Paris Hilton.

The Discovery of Interferon, the First Cytokine, by Alick Isaacs and Jean Lindenmann in 1957 (#7).

These last 2 articles are unique – in that the one about the Hans Selye stress concept, and the one about the discovery of interferon, are written by Profs. Istvan Berczi and Derek Burke, two investigators who had the chance to work along Hans Selye and Alick Isaacs, respectively.

Interestingly, the short blog-style post Chronic Urticaria Linked to a Th2/Th17 Shift in Skin Lesions (#15) was our 2nd most unexpected article on the most-read list. This may simply indicate a relatively high readership interest about new evolving immune or neuroendocrine-immune mechanisms contributing to urticaria such as T helper (Th)2 and/or Th17 shift. Or, in addition, mechanisms involving the association between psychological stress and urticaria. This may also indicate a similar mechanism in Graves’ disease as outlined in another BrainImmune article entitled: ‘Stress-Induced Th2 Shift & Thyroid Autoimmunity: Unifying Hypothesis’.

According to the data we’ve compiled from our top 20 list, about  60-70% of our remaining articles pertain to the real, bona fide brain– and stress–immune interactions or neuroendocrine immunology. It appears that there is a continued interest about the role of lymphoid organs innervation, or the effect of different hormones and neuromediators on immune system’s function or homeostasis.

This includes the interactions between thyroid hormones, stress and the immune system leading to a Th1/Th2 imbalance or an increment in Th17/Treg ratio. Or, for example, the role of sex steroids hormones in immunoregulation or autoimmune disease activity, and the Nerve Growth Factor-inflammation interactions.

Importantly, the top 20 list also involves several articles suggesting the evolving links between:

Cross-talk dopamine and innate immunity figure 2‘The dopaminergic system and innate immunity’

‘Inflammation and fatigue’

‘Endogenous catecholamines and immune cells’

‘β2-adrenergic agonists and Parkinson’s disease’

‘The innate immune system and psychological stress’

‘Afferent vagus nerve stimulation and improvement of experimental joint inflammation’

In any case, here are the 20 most popular BrainImmune stories of 2018:

1.  Walter Cannon: Homeostasis, the Fight-or-Flight Response, the Sympathoadrenal System, and the Wisdom of the Body

By David Goldstein

2. The Evolving Link between Social Media Addiction and Depression in Young Adults

By Ilia Elenkov

3. The Discovery of Adrenaline

By Ashley Grossman and David Jessop

4. Thyroid Hormone Modulation of Immune Responses in Physiologic and Stressful Conditions: Implications for Thyroid Diseases

By Graciela Cremaschi and Ana Maria Genaro

5. Claude Bernard, the Father of Modern Physiology and Experimental Medicine

By Vincent Geenen

6. Sex Hormones and Immunoregulation

By Marijke Faas, Paul de Vos and Barbro Melgert

7. The Discovery of Interferon, the First Cytokine, by Alick Isaacs and Jean Lindenmann in 1957

By Derek Burke

8. Innervation of the Human Thymus and Spleen – an Overview

By Valsamo Anagnostou, Ipatia Doussis-Anagnostopoulou, Dina Tiniakos and Christos Kittas

9. Hans Selye and the Birth of the Stress Concept

By Istvan Berczi

10. The Cross-talk between the Dopaminergic System and Innate Immunity: An Evolving Concept

By Monica Pinoli

Edith Piaf and arthritis11. Sex Steroids Hormones and Autoimmune Disease Activity

By Antonio Martocchia, Silvia Raja, Manuela Stefanelli, Anna Cocca and Paolo Falaschi

12. Understanding the Role of Inflammation in Fatigue Requires Multidimensional Assessments

By Julie Lasselin, Bianka Karshikoff and Tina Sundelin

13. Bartolomeo Eustachius and the Discovery of Adrenal Glands

By Rita Businaro and Angela Tagliani

14. Endogenous Catecholamines in Immune Cells: Discovery, Functions And Clinical Potential as Therapeutic Targets

By Marco Cosentino, Natasa Kustrimovic and Franca Marino

15. Chronic Urticaria Linked to a Th2/Th17 Shift in Skin Lesions

By Ilia Elenkov

16. β2-Adrenergic Agonists for Parkinson’s Disease: Repurposing Drugs at the Crossroad of the Brain and the Immune System

By Marco Cosentino, Natasa Kustrimovic and Franca Marino

17. The Innate Immune System Senses Psychological Stress through the ATP/P2X7R-Inflammasome (NLRP3) Cascade

By Javier Caso

18. Afferent Vagus Nerve Stimulation Activates Brain Locus Coeruleus and Improves Experimental Joint Inflammation

By Gabriel Bassi

19. Nerve Growth Factor and Inflammation: A Complex Bidirectional Interaction

By Luisa Bracci-Laudiero

20. The Glucocorticoid Receptor

By Tomoshige Kino

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