Evidence browser

Moxibustion upregulates hippocampal progranulin expression.

Yi, Tao, Qi, Li, Li, Ji et al.·Neural regeneration research·2016

This study tested whether moxibustion, a traditional Chinese medicine technique using heat from burning herbs, could help rats with chronic fatigue syndrome. Researchers found that moxibustion reduced stress hormone levels and increased a protective protein in the brain called progranulin, which appeared to improve the rats' symptoms of fatigue and low mood.

Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome.

Zhang, Zi-Teng, Du, Xiu-Ming, Ma, Xiu-Juan et al.·Journal of neuroinflammation·2016

Researchers created a mouse model of fatigue by exposing mice to immune stress (a bacterial compound) combined with physical stress. They found that a specific immune protein called NLRP3 becomes active in the brain during fatigue, and that blocking this protein reduced fatigue symptoms. This suggests that controlling this immune pathway might help treat fatigue in conditions like ME/CFS.

E3 PreliminaryReviewPEM not requiredReview-Narrative

The Many Neuroprogressive Actions of Tryptophan Catabolites (TRYCATs) that may be Associated with the Pathophysiology of Neuro-Immune Disorders.

Morris, Gerwyn, Carvalho, André F, Anderson, George et al.·Current pharmaceutical design·2016

When the body has chronic inflammation and immune activation, it breaks down an amino acid called tryptophan differently than usual, creating byproducts called TRYCATs. Some of these byproducts can damage nerve cells and mitochondria (the energy factories in cells), while others may protect the brain but at the cost of causing brain fog and emotional problems. This review examines how this abnormal tryptophan breakdown might contribute to ME/CFS and other neurological conditions.

NeuroinflammationEnergy MetabolismImmune System

The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.

Morris, Gerwyn, Berk, Michael, Galecki, Piotr et al.·Molecular neurobiology·2016

This review examines why people with ME/CFS and similar immune-based illnesses experience severe, disabling fatigue. The authors identify multiple biological pathways that may contribute to this fatigue, including excessive inflammation, problems with how cells produce energy, and chemical imbalances in the brain and muscles. The fatigue appears to result from a complex interaction between the immune system, energy production, and brain function rather than a single cause.

E3 PreliminaryReviewPEM not requiredReview-Narrative

The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome.

Morris, Gerwyn, Berk, Michael, Carvalho, André F et al.·Current pharmaceutical design·2016

This review explores how problems with the gut barrier and changes in gut bacteria may trigger widespread immune activation and brain inflammation in ME/CFS and other autoimmune diseases. When the intestinal lining becomes more permeable (leaky), bacteria and their products can enter the bloodstream, potentially causing the fatigue, brain fog, and other symptoms characteristic of ME/CFS.

NeuroinflammationEnergy MetabolismImmune System

The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.

Morris, Gerwyn, Walder, Ken, Puri, Basant K et al.·Molecular neurobiology·2016

This review explains how harmful molecules called oxidative and nitrosative stress damage specific fatty structures in cells that are important for cell communication and brain function. These damaged structures may contribute to ME/CFS, along with other conditions affecting the brain and immune system. The authors suggest that omega-3 fatty acid supplements might help restore these damaged cellular structures.

Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses.

Morris, Gerwyn, Berk, Michael, Walder, Ken et al.·BMC medicine·2015

This review proposes that ME/CFS fatigue may be caused by ongoing inflammation and immune system activation in the body, which then damages the brain's support cells (astrocytes) and energy-producing structures (mitochondria). The authors suggest that ME/CFS shares similar biological mechanisms with other inflammatory diseases like multiple sclerosis and lupus, and recommend that ME/CFS patients be tested for immune activation and receive specific brain imaging to look for evidence of inflammation.

NeuroinflammationGut MicrobiomeImmune System

The Role of Toll-Like Receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A New Promising Therapeutic Approach?

Gambuzza, Maria Elsa, Salmeri, Francesca Maria, Soraci, Luca et al.·CNS & neurological disorders drug targets·2015

This review examines how certain immune system sensors called Toll-like receptors (TLRs) may contribute to ME/CFS. These receptors sit on cells in the gut and detect bacteria and other microbes, triggering inflammation that may spread to the brain and cause fatigue and other symptoms. The researchers suggest that targeting these TLRs with new medications might help reduce inflammation and improve symptoms.

Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.

Theoharides, Theoharis C, Stewart, Julia M, Hatziagelaki, Erifili et al.·Frontiers in neuroscience·2015

This review discusses 'brain fog'—trouble thinking clearly, concentrating, and remembering—which affects people with ME/CFS and other conditions. Researchers suggest brain fog may be caused by inflammation and immune cells releasing harmful chemicals in the brain. A natural compound called luteolin, which has anti-inflammatory properties, shows promise in early studies for reducing brain fog symptoms.

E3 PreliminaryMechanismPEM unclearCross-Sectional

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study.

Nakatomi, Yasuhito, Mizuno, Kei, Ishii, Akira et al.·Journal of nuclear medicine : official publication, Society of Nuclear Medicine·2014

This study used a special brain imaging technique called PET scans to look for signs of inflammation in the brains of ME/CFS patients. Researchers found that people with ME/CFS had higher levels of brain inflammation markers in several key brain regions compared to healthy controls. The amount of inflammation was linked to how severe patients' cognitive problems, pain, and depression were.

The glutathione system: a new drug target in neuroimmune disorders.

Morris, Gerwyn, Anderson, George, Dean, Olivia et al.·Molecular neurobiology·2014

This review examines glutathione (GSH), a naturally occurring substance in our cells that protects against damage and helps our immune system work properly. When glutathione levels drop, cells become more stressed and inflamed, which may contribute to ME/CFS and other conditions affecting the brain and immune system. The authors suggest several potential treatments—including supplements like N-acetyl cysteine and natural compounds like curcumin—that might help restore glutathione levels.

Induction of interleukin-1β by activated microglia is a prerequisite for immunologically induced fatigue.

Ifuku, Masataka, Hossain, Shamim M, Noda, Mami et al.·The European journal of neuroscience·2014

This study used rats to understand how an immune trigger (a synthetic viral mimic) causes prolonged fatigue. Researchers found that when this trigger activates immune cells in the brain called microglia, they release a chemical messenger called IL-1β that affects how the brain handles serotonin, leading to reduced activity and fatigue-like behavior.

A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation.

Yasui, Masaya, Yoshimura, Takashi, Takeuchi, So et al.·Glia·2014

This study used rats exposed to continuous stress to model ME/CFS and fibromyalgia, finding that stress caused pain sensitivity without any actual tissue damage or infection. The researchers discovered that immune cells in the spinal cord called microglia became activated in stressed animals, and blocking this activation with a drug called minocycline reduced their pain. This suggests that abnormal pain in ME/CFS may stem from brain and spinal cord inflammation rather than damage to muscles or skin.

E3 PreliminaryMechanismPEM unclearObservational

Clinical features in patients with long-lasting macrophagic myofasciitis.

Rigolet, Muriel, Aouizerate, Jessie, Couette, Maryline et al.·Frontiers in neurology·2014

This study describes macrophagic myofasciitis (MMF), a condition where aluminum from vaccines persists in muscle tissue and causes long-lasting symptoms similar to ME/CFS, including widespread pain, severe fatigue, and significant problems with thinking and memory. Patients show patterns of brain abnormalities on imaging scans, and their cognitive problems appear to be caused by brain dysfunction rather than just pain or depression. The researchers found that standard treatments don't work well for these patients, making their condition particularly disabling.

NeuroinflammationGut MicrobiomeImmune System

The gut microbiome and the brain.

Galland, Leo·Journal of medicinal food·2014

Your gut bacteria can communicate with your brain in several ways: they produce substances that trigger your immune system, create chemicals that affect your mood and sleep, and send signals directly to your brain through a major nerve called the vagus nerve. When the balance of gut bacteria is disrupted, this communication can go wrong and may contribute to problems like chronic fatigue, brain fog, and mood changes.

Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).

Morris, Gerwyn, Maes, Michael·Current neuropharmacology·2014

This study proposes that ME/CFS involves a harmful cycle where the body's immune system becomes overactive and produces damaging molecules called oxidative stress. These problems can be triggered by infections, gut bacteria leaking into the bloodstream, or problems with the energy-producing parts of cells called mitochondria. Once started, this cycle feeds on itself, causing brain inflammation, reduced blood flow to the brain, and damage to cells throughout the body.

E3 PreliminaryReviewPEM requiredReview-Narrative

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

Morris, Gerwyn, Maes, Michael·Metabolic brain disease·2013

This study proposes a theory about how ME/CFS develops and persists. The researchers suggest that an initial infection triggers the immune system, which then gets stuck in an overactive state even after the infection is cleared. This causes ongoing inflammation, energy problems in cells, and damage to the nervous system, leading to the characteristic symptoms including post-exertional malaise (feeling worse after activity).

NeuroinflammationAutonomic Nervous SystemImmune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM unclearEditorial

New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome.

Pontari, Michel, Giusto, Laura·Current opinion in urology·2013

This article discusses how chronic prostatitis and chronic pelvic pain syndrome in men can present differently—some men have pain localized to the pelvic area, while others experience widespread body symptoms similar to other chronic conditions. The authors review new treatment options including physical therapy, acupuncture, psychological support, and medications, and note that these conditions often occur alongside other chronic pain disorders like fibromyalgia and chronic fatigue syndrome.

E3 PreliminaryMechanismPEM unclearMechanistic

Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins.

De Meirleir, Kenny L, Khaiboullina, Svetlana F, Frémont, Marc et al.·In vivo (Athens, Greece)·2013

Researchers found that a specific type of immune cell in the gut (called plasmacytoid dendritic cells) reacts to remnants of ancient viral DNA in 8 out of 12 ME/CFS patients, but not in healthy controls. These cells appear to be displaying signs of viral proteins on their surface, which suggests the gut may be involved in triggering immune problems seen in ME/CFS.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor.

Yamamoto, Shigeyuki, Ouchi, Yasuomi, Nakatsuka, Daisaku et al.·PloS one·2012

Some people with ME/CFS have antibodies in their blood that target a chemical receptor in the brain called the muscarinic cholinergic receptor. This study used brain imaging (PET scans) to compare the brains of ME/CFS patients with and without these antibodies. Patients with these antibodies showed lower levels of these receptors in their brains, but this difference did not affect their thinking or memory performance.