In addition, some disorders; such as rheumatoid arthritis, gastrointestinal inflammation, chronic obstructive pulmonary disease, MS, chronic fatigue syndrome, dermatitis, diabetes, cancer, dementia, rheumatoid arthritis and/or myalgic encephalomyelitis (CFS/ME); can trigger neuroinflammation (Schref et al. 2018, Sun et al. 2022)
☆ Brain fog (if you are a woman see note below)
☆ Loss of brain function
☆ Some forms of dementia
☆ Anger, rage, frustration for no reason
☆ Crying for no reason
☆ Depression
☆ Confusion
☆ Brain fatigue
☆ Poor mental focus
☆ Unclear thoughts
Please seek help immediately if you suddenly have high fever, seizures, headache, stiff neck and back, hallucinations and/or mental confusion. It could be acute brain inflammation which can be fatal!
If your regular doctor refuses to test hormone concentrations and/or prescribe hormones check out all the internet doctors that can help you obtain proper treatment with bioidentical hormones. Perimenopause can start in early 30's or even younger for some women!
Many doctors try to give you antidepressants when your body really needs estrogen.
Here's an article with some of the companies offering treatment. Some are covered by insurance. If you google something like "online doctors prescribe bioidentical hormones" you will get even more options. Here's another list of bioidentical hormone doctors in the USA and Canada.
PSA: men can suffer from testosterone deficiency; many of these places offer treatment for guys too.
Inflammation can spread from the body into the brain in a process called peripheral inflammation-induced neuroinflammation (try saying that three times fast!). Basically, this means that inflammation from outside the brain (peripheral) causes or induces inflammation inside the brain. This may happen for several reasons (discussion in Sun et al. 2022):
1) Blood-brain barrier (BBB) is disrupted. The blood brain barrier is a collection of cells that surround the blood vessels in the brain and control what enters the brain. Think of them as the Club Brain's tough bouncers. Normally, only the most elite get invited to party in the brain. Unfortunately, chronic inflammation can break down the BBB. This means Club Brain's bouncers are all on a smoke break, leaving the central nervous system (CNS) susceptible to unwanted substances and shady characters coming into the brain. This causes inflammation.
2) Autonomic nerves are influenced via the organ-brain axis. The autonomic nervous system (ANS) handles all the body functions you don't have to or want to think about; like heart rate, digestion, and blood pressure. The organ-brain axis is the collection of nerves that directs bidirectional communication between the brain and the gut; it may also be influenced by gut bacteria (Carabotti et al. 2015). This body-brain interaction regulates body inflammation and immune responses (Jin et al. 2024).
When nerves are activated by whole body inflammation, the sympathetic nervous system (SNS) becomes over activated and sympathetic nerve fibers are lost. An over activated SNS results in a flight, flee or freeze reaction. This causes an increase in immune cells as well as increases in heart rate, cardiac output, blood pressure, and blood glucose (Pongratz and Straub 2023).
3) Glial cells are activated by signs of danger in their environment. Systemic inflammation produces compounds like lipopolysaccharide (LPS) which activate glial cells in the brain. Activated glial cells become enthusiastic immune cells which cause inflammation. Excess LPS also increases brain tumor necrosis factor alpha (TNF-a) which promotes inflammation (Hoogland et al. 2015).
Neuroinflammation can also be caused by: a viral infection, inflammation from peripheral organs, autoimmune diseases, severe illness, metabolic disorders, mental stress, and lifestyle choices (Sun et al. 2022).
Note: Not all inflammation is bad; your body uses inflammatory cytokines and molecules as cellular messengers and signals. It also uses inflammation to signal the immune system that it requires help because of injury or pathogens (Chen et al. 2017).
What do you think would happen in a city if most of the nurses, trash collectors, food service workers and police force suddenly stopped working to cosplay Rambo: Citizens Attack Back PLUS all the traffic signals and the internet went down? This is what is going on in your brain when glial cells become activated due to inflammation.
Glial cells, also called neuroglia or glia, make up over one half of all brain cells. They are the nervous system's supporting staff, trainers, and advisors. These hard working cells provide physical and metabolic support to neurons in the central and peripheral nervous system (CNS and PNS). Normally peaceful and helpful, glial cells can change their function and activate due to brain changes and traumas (good discussion in Hassanzadeh et al. 2021). Activated glial cells are similar to violent untrained immune cells. They spew out harmful chemicals and can cause cell damage and increase inflammation.
You can think of healthy glia as a combination of a physical therapist, nurse, occupational therapist, and emotional support cell. Some glial cells even curl up around injured brain cells and stroke them to help them heal. They help integrate sensory information like touch, sight, sound and vibrations with brain neurons; this directs neurons how to respond to sensory input (Liu et al. 2023, Ray et al. 2024). Glial cells include astrocytes, microglia, ependymal cells, radial glia, satellite cells and oligodendrocytes.
TMI causes brain inflammation. When brain cells are injured, inflammation occurs due to glial cell activation. This causes an increase in inflammatory chemical mediators and peripheral immune cells (Zhao et al. 2023). Chemical mediators are molecules that actively contribute to, moderate and adjust the inflammatory response. They can cause inflammation or reduce inflammation.
Type 2 diabetes (T2D), fatty liver, and other metabolic disorders can cause whole body and brain inflammation. This is a mutual death spiral situation where inflammation causes metabolic disfunction and metabolic disfunction causes inflammation. Click here to see how this whole cycle can be triggered by excess fat gain.
People who are exposed to trauma can develop PTSD. For more see PTSD. While the actual number of people with PTSD is unknown, most reliable sources estimate that 6-8% of the population has or had PTSD. This number is higher in women and veterans. Around 3.5% of people have the criteria for cPTSD. It can develop at any age but is more common in people who had severe trauma during childhood.
There is a reciprocal link between inflammation and PTSD. People with PTSD had higher amounts of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-17, nuclear factor-κB, interferon gamma, and C-reactive protein when compared with healthy people (Lee et al. 2022, Sun et al. 2021). In addition, several studies reported that people with higher levels of these inflammatory chemicals had more severe cases of PTSD (Kim et al. 2020, good discussion in Lee et al. 2022).
Inflammation can even change the brain's structure which may account for the behavioral changes seen in PTSD. Changes in inflammatory markers in PTSD studies were associated with structural and functional alterations in brain regions such as the hippocampus, amygdala, and frontal cortex. These brain areas help regulate stress and emotion (discussion in Kim et al. 2020).
Your body attacks itself in autoimmune disorders such as multiple sclerosis (MS), autoimmune encephalitis, neuromyelitis optica (NMO) and systemic lupus erythematosus (SLE). This immune attack causes abnormal immune responses in the nervous system, including the brain, resulting in brain damage and inflammation.
Inflammatory cytokines; especially the IL family, IL-1, IL-6, and IL-17; are involved in the pathogenesis of many autoimmune diseases as well as in inflammation.
Some autoimmune disorders specifically target the brain and in others the brain is collateral damage. An immune attack on the brain can result in seizures, cognitive changes (hallucinations, memory loss, catatonia) and behavior issues.
You may be thinking that you have seen the interleukin (IL) family mentioned in this website before. That is because some family members are heavily involved in inflammation. They are often measured and used as a marker of chronic inflammation.
An interleukin is an emitted protein that binds to a specific receptor and is involved in leukocyte (white blood cell) intercellular communication. Instead of texting, immune and inflammatory cells communicate using IL. Sometimes they use it for good and sometimes they are just throwing shade.
The IL family is produced by immune cells. Different subsets of immune cells produce different cytokine groupings. There are over 60 cytokines in the IL group. If you are interested in the IL ancestry chart check out Akdis et al. 2016 for a family tree.
IL are not all bad; we need them! Defects in IL signaling pathways can cause severe combined immunodeficiency (SCID) diseases. Like many cytokines, the key is having the proper balance.
There is evidence that inflammation plays a major role in mood disorders (Benedetti et al. 2020). People who have systemic autoimmune diseases characterized by inflammation; such as rheumatoid arthritis, Ankylosing spondylitis, lupus, and Sjogren's syndrome; are more prone to mood disorders. Cytokines, small molecules secreted by immune system cells, seem to be involved in mood disorders (discussion in Benedetti et al. 2020).
In addition, recent research suggests that neuroinflammation leads to neural-circuit dysfunction which can be associated with depression (see more about this in Han and Ham et al. 2021).
COVID-19 can take a toll on your brain. British researchers from the COVID-19 Clinical Neuroscience Study (COVID-CNS) found that 351 patients had evidence of long-term brain injury a YEAR after being hospitalized with COVID-19 (check it out in this website). Long-COVID is characterized by traumatic brain injury (TBI) (Agoston 2024). Brain injuries can cause inflammation.
A small pilot study (age 25-65 years, all had COVID) found that 10 people with symptoms of Long COVID had less nerve growth factor (NGF) and higher amounts of IL-10, a marker of inflammation, when compared to 7 people without Long COVID (Lawrence et al. 2025). NGF is involved with higher-level cognitive functions requiring mental flexibility and memory. It is a key player in neuron development and maintenance of brain plasticity. Brain plasticity, also called neuroplasticity, is the brain's ability to adapt and reorganize after damage.
What you do influences your brain health. Mental well being is positively associated with healthy lifestyle habits such as exercise, sleeping enough, eating a low inflammatory diet, and having social connections (discussion Mintzer et al. 2019). Likewise, a lifestyle that includes high stress, smoking, drinking, and limited social connections is associated with poorer mental health. Chronic stress and anxiety disorders have been linked to brain inflammation (Won and Kim 2020).
Tobacco smoking may increase the risk of neurovascular diseases (such as stroke and aneurysms), metabolic diseases and neuropsychiatric diseases. Neuropsychiatric diseases include anxiety disorders, depression, dementia, cognitive decline, schizophrenia, psychosis, and suicidal behavior. This may be due to central nervous system changes (CNS) changes in inflammatory and oxidative stress pathways (Hahad et al. 2021). Harmful chemicals in smoke can also cross the blood brain barrier to the brain.
Likewise, chronic cannabis smoking has adverse affects on mental health. Studies have shown that regular smokers have an increase in depression and anxiety; higher risk of psychosis; higher risk of schizophrenia; greater cognitive impairment; and a change in how they interpret the environment (perceptual alteration) (discussion in Hazzard et al. 2024).
Cannabis is particularly damaging to people under 25 years old.
Learn more about the harm of smoking and vaping here.
Studies showed alcohol use causes liver and brain inflammatory responses that are associated with brain shrinkage and other abnormalities. In rats and in people, alcohol use causes liver inflammation. Liver inflammation is correlated with brain shrinkage, brain damage, white matter changes, and overall brain inflammation. The very same structural brain damage and white matter abnormalities documented in alcoholic rats were seen in CAT scans of human alcoholics (discussion in Lanquetin et al. 2021).
JoAnn Z (57 year old woman): "My ex-husband definitely had damaged his brain due to alcohol. He would repeat questions; I could tell him something ten times and he’d turn around ten minutes later and ask me again. He would just straight up imagine whole conversations and events and then he be irritated when I didn't know what he was talking about. He would forget actual conversations we’d have and accuse me of lying. He’s sober now but still forgets things all the time, has lost his drive and motivation, and doesn’t seem to grasp simple concepts."
Joint inflammation from rheumatoid arthritis (RA) can cause brain inflammation by changing the brain. Schrepf et al. (2018) found that higher levels of body inflammation caused by RA were associated with reduced inferior parietal lobule (IPL) grey matter. The inferior parietal lobule is an under-appreciated part of the brain involved in math operations, attention, language, social cognition, pattern learning, and action processing. Grey matter is the part of your brain concentrated with neuronal cells. It allows you to think, reason, control movement, access memories and process outside stimulus.
Higher levels of body inflammation were also associated with new connections developing between different parts of the brain. Scans showed increased connections between the IPL, the medial prefrontal cortex (mPFC), and multiple brain networks. The mPFC is involved in inhibitory control, attention, habit formation and working, and memory. It is believed that chronic inflammation establishes new patterns in the neural (brain) network which leads to brain inflammation. In other words, acute inflammation changes established neural networks which promotes changes in health and in behavior.
Indeed, the new patterns of brain network connectivity prompted by chronic inflammatory conditions predicted the extent of people's pain, fatigue, lethargy, and cognitive dysfunction. Increased brain changes led to worse symptoms in RA (Schrepf et al. 2018).
*Names and some minor identifying details in all stories in this website are changed to protect people's privacy.
This information is for informational purposes only and does not constitute medical advice, diagnosis, or treatment.
Agoston DV. Traumatic Brain Injury in the Long-COVID Era. Neurotrauma Rep. 2024 Jan 30;5(1):81-94. doi: 10.1089/neur.2023.0067. Full article.
Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, Duan S, Eiwegger T, Eljaszewicz A, Ferstl R, Frei R, Garbani M, Globinska A, Hess L, Huitema C, Kubo T, Komlosi Z, Konieczna P, Kovacs N, Kucuksezer UC, Meyer N, Morita H, Olzhausen J, O'Mahony L, Pezer M, Prati M, Rebane A, Rhyner C, Rinaldi A, Sokolowska M, Stanic B, Sugita K, Treis A, van de Veen W, Wanke K, Wawrzyniak M, Wawrzyniak P, Wirz OF, Zakzuk JS, Akdis CA. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-a: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016 Oct;138(4):984-1010. doi: 10.1016/j.jaci.2016.06.033. Full article.
Benedetti F, Aggio V, Pratesi ML, Greco G, Furlan R. Neuroinflammation in Bipolar Depression. Front Psychiatry. 2020 Feb 26;11:71. doi: 10.3389/fpsyt.2020.00071. Full article.
Hahad O, Daiber A, Michal M, Kuntic M, Lieb K, Beutel M, Münzel T. Smoking and Neuropsychiatric Disease-Associations and Underlying Mechanisms. Int J Mol Sci. 2021 Jul 6;22(14):7272. doi: 10.3390/ijms22147272. Full article.
Han KM, Ham BJ. How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies. J Clin Neurol. 2021 Oct;17(4):503-515. doi: 10.3988/jcn.2021.17.4.503. Full article.
Kim TD, Lee S, Yoon S. Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective. Antioxidants (Basel). 2020 Jan 26;9(2):107. doi: 10.3390/antiox9020107. Full article.
Lanquetin A, Leclercq S, de Timary P, Segobin S, Naveau M, Coulbault L, Maccioni P, Lorrai I, Colombo G, Vivien D, Rubio M, Pitel AL. Role of inflammation in alcohol-related brain abnormalities: a translational study. Brain Commun. 2021 Jul 16;3(3):fcab154. doi: 10.1093/braincomms/fcab154. Full article.
Lawrence MR, Arnetz JE, Counts SE, Ahmed A, Arnetz BB (2025) Self-reported health, neuropsychological tests and biomarkers in fully recovered COVID-19 patients vs patients with post-COVID cognitive symptoms: A pilot study. PLoS ONE 20(5): e0315486. https://doi.org/10.1371/journal.pone.0315486 Full article.
Lee DH, Lee JY, Hong DY, Lee EC, Park SW, Lee MR, Oh JS. Neuroinflammation in Post-Traumatic Stress Disorder. Biomedicines. 2022 Apr 20;10(5):953. doi: 10.3390/biomedicines10050953. Full article.
Mintzer J, Donovan KA, Kindy AZ, Lock SL, Chura LR, Barracca N. Lifestyle Choices and Brain Health. Front Med (Lausanne). 2019 Oct 4;6:204. doi: 10.3389/fmed.2019.00204. Full article.
Schrepf A, Kaplan CM, Ichesco E, Larkin T, Harte SE, Harris RE, Murray AD, Waiter GD, Clauw DJ, Basu N. A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis. Nat Commun. 2018 Jun 8;9(1):2243. doi: 10.1038/s41467-018-04648-0. Full article.
Sun Y, Qu Y, Zhu J. The Relationship Between Inflammation and Post-traumatic Stress Disorder. Front Psychiatry. 2021 Aug 11;12:707543. doi: 10.3389/fpsyt.2021.707543. Full article.
Won E, Kim YK. Neuroinflammation-Associated Alterations of the Brain as Potential Neural Biomarkers in Anxiety Disorders. Int J Mol Sci. 2020 Sep 7;21(18):6546. doi: 10.3390/ijms21186546. Full article.
Zhao Q, Li H, Li H, Xie F, Zhang J. Research progress of neuroinflammation-related cells in traumatic brain injury: A review. Medicine (Baltimore). 2023 Jun 23;102(25):e34009. doi: 10.1097/MD.0000000000034009. Full article.