Brain Inflammation

Brain Inflammation: Understanding Its Causes, Hormonal Effects, and How to Manage It

Brain inflammation, or neuroinflammation, is increasingly recognized as a key player in a wide range of neurological, psychiatric, and hormonal disorders. Whether caused by injury, infection, environmental toxins, or chronic stress, inflammation in the brain can disrupt normal communication, impair hormone signaling, and lead to widespread dysfunction.

What Is Brain Inflammation?

Neuroinflammation involves activation of the brain's immune cells—microglia and astrocytes—in response to perceived threats. While short-term inflammation helps repair injury, chronic inflammation becomes harmful, damaging neurons and impairing the blood-brain barrier (BBB).

Causes of Brain Inflammation

Traumatic brain injury (TBI)

Leaky blood-brain barrier (BBB permeability from infection, head trauma, or chronic stress)

Chronic stress or HPA axis dysfunction

Environmental toxins (mold, heavy metals, pesticides)

Gut-brain axis dysfunction (leaky gut, SIBO, LPS endotoxemia)

Poor diet (high sugar, omega-6 fats, nutrient deficiencies)

Neurodegenerative diseases (Alzheimer’s, Parkinson’s)

Genetic predisposition

How Brain Inflammation Affects Hormones

Impact on the Hypothalamus and Pituitary

Chronic inflammation can disrupt hypothalamic-pituitary signaling, leading to:

Suppression of GnRH (gonadotropin-releasing hormone)

Low or dysregulated FSH and LH (leading to infertility, low testosterone/estrogen)

Impaired TSH, ACTH, and GH signaling

 Hormonal Imbalances From Neuroinflammation

Low testosterone, estrogen, and progesterone

Altered cortisol rhythms

Low thyroid function despite normal labs

Poor dopamine and serotonin synthesis

Neurotransmitters and Mood:  Dopamine, Serotonin & Anxiety

Inflammation suppresses dopamine production and receptor sensitivity

→ linked to low motivation, fatigue, and depression

Increases glutamate (excitotoxicity) and decreases GABA → anxiety, agitation

Cytokines (e.g., IL-6, TNF-α) impair serotonin pathways

May cause SSRI resistance in depression due to inflammatory interference

Genetic Factors That Contribute

Some genes increase vulnerability to brain inflammation and its hormonal consequences:

APOE4 – higher Alzheimer’s and neuroinflammation risk

MTHFR (C677T, A1298C) – impaired methylation and detox

COMT – affects dopamine clearance, stress response

IL-6, TNF-α variants – upregulate inflammatory cytokine production

NR3C1 – alters glucocorticoid receptor sensitivity

DAO, MAOA – histamine/amine metabolism and mood regulation

The Role of Pregnenolone and Progesterone

Emerging studies suggest both have neuroprotective and anti-inflammatory effects:

 Pregnenolone:

Enhances myelin repair

Modulates GABA and NMDA receptors

Improves cognition and memory

Reduces microglial activation

 Progesterone:

Shown to reduce brain swelling post-TBI

Promotes neurogenesis and remyelination

Modulates inflammation and oxidative stress

May support pituitary and hypothalamic health in both men and women

Diseases and Disorders Linked to Brain Inflammation

Alzheimer’s disease

Parkinson’s disease

Depression and anxiety

Bipolar disorder

PTSD and trauma disorders

ADHD

Autism spectrum disorder (ASD)

Chronic fatigue syndrome (ME/CFS)

Fibromyalgia

Hypothalamic amenorrhea / infertility

Hashimoto’s thyroiditis (via HPT axis suppression)

How to Manage Brain Inflammation

Identify and remove triggers: mold, infections, stress, poor sleep, high blood sugar

Heal the gut: reduce endotoxins, support tight junctions (e.g., glutamine, zinc carnosine)

Support methylation and detox: B12, methylfolate, NAC, magnesium

Balance neurotransmitters: adaptogens, amino acids, light therapy, mindfulness

Hormone replacement if needed: progesterone, pregnenolone, DHEA (under supervision)

Targeted supplements:

Omega-3s (DHA/EPA), Curcumin, Lion’s mane mushroom

Phosphatidylserine, Low-dose naltrexone (LDN)

Fun Fact & Final Thoughts

The brain has its own lymphatic system—called the glymphatic system—which activates during sleep to clear waste and inflammation. Sleep is literally brain detox time.

Brain inflammation is more than a neurological issue—it affects hormones, mood, fertility, and long-term cognitive health. Understanding its root causes and targeting inflammation through lifestyle, nutrition, and sometimes hormones or peptides can restore balance to both the brain and body.

If you're struggling with unexplained fatigue, mood changes, or hormonal dysfunction, consider looking at the brain—not just the body.