Chronic Inflammation & Brain Health

Posted: December, 2022
Author: Katie Donnelly, Adv Dip HSc Naturopathy

Brain inflammation is linked to disease states including Alzheimer’s, Parkinson’s, and dementia. However, systemic inflammation, chronic illness and stress also contribute to neurodegeneration via direct and efferent pathways. Phytotherapy can help re-regulate this response and mitigate the cognitive impact of inflammation.

The Equilibrium State

Acute neuroinflammation is a positive response to infectious microbes or injury and is necessary for the restoration of healthy neurons. Homeostatic inflammatory responses in the brain are largely regulated by glial cells. Microglia and astrocytes help to regulate neuron connection, communication, and neurogenesis and maintain the blood-brain barrier (BBB) integrity.

Microglia have high sensitivity to pathogens and tissue damage. Local and systemic inflammatory signals trigger microglia via Toll-Like Receptor-4 to release pro-inflammatory cytokines. This includes interleukin 1 beta (IL-1β), tumour necrosis factor-alpha (TNF-α), and reactive oxygen species (ROS). Astrocytes are activated, primarily by Il1- β, and initiate the classical phase of the complement cascade.¹

This pro-inflammatory period exists as part of the innate immune response and operates on a negative feedback loop. In a healthy response, environmental changes then encourage microglia and astrocytes to switch to releasing anti-inflammatory mediators. This aids the recovery and preservation of neurons.²

System Dysfunction

In chronic inflammation, this system commonly malfunctions. In ongoing psychological stress, microglia activation causes an accumulation of monocytes and macrophages. This perpetuates the inflammatory cycle and contributes to the resulting cognitive decline.

The mitochondria are also negatively impacted by increased ROS. The deoxyribonucleic acid (DNA) of mitochondria becomes altered, leaving damaged mitochondria unable to produce adenine triphosphate. The ROS released by mitochondria then continue on and become a driver of the inflammatory cycle. This directly impacts cellular energy and contributes to metabolic, cardiovascular, and neurological disease.³

Peripheral Inflammation and the Brain

The central nervous system (CNS) interprets stress from psychological and autonomic cues. As part of this response, inflammatory mediators access circumventricular organs via the bloodstream.⁴ As such, gastrointestinal ailments, chronic fatigue syndrome, cardiovascular disease, and chronic obstructive pulmonary disease contribute to neuroinflammation.2

Typically, peripheral cytokines and chemokines do not pass through the BBB due to a lack of mediating receptors and tight junctions preventing entry. A primary BBB protein, claudin-5, dictates overall junction permeability. However, IL1-β alters the endothelium dispersion. Consistent pro-inflammatory cytokine exposure, therefore, leaves the BBB increasingly penetrable. Activated astrocytes also impact claudin-5 presence, while ROS damages cellular structures.⁴

In chronic inflammation and pre-existing disease, lymphocytes can pass into the cerebral space, leaving the brain vulnerable to disease development or progression. This is particularly relative to previous brain injuries, such as stroke.

Peripheral inflammation also relies upon negative feedback loops, which are disturbed in the chronic activation of inflammatory pathways. Cortisol, stimulated by adrenocorticotrophin hormone (ACTH) via the hypothalamic-pituitary-adrenal (HPA) axis, typically binds with mineralocorticoid receptors. These receptors are numerous throughout the hippocampus and amygdala.⁵ When levels rise, cortisol binds to the lower-affinity glucocorticoid receptors to stop ACTH secretion.6 In systemic inflammation, reduced glucocorticoid receptors are present, slowing the feedback loop and increasing baseline cortisol levels.⁶

Studies show impaired memory, recall, and brain fog associated with chronically high cortisol. This can disrupt sleep patterns, increase bone fragility and muscle weakness, and disturb the gut mucosa.⁷

The Gut-Brain Axis

The gut-brain axis describes bi-directional communication between the microbiome and the CNS that enables balance in each system. This information sharing occurs between the vagus nerve and HPA signalling. Furthermore, neuroplasticity and genetic structure are influenced by short-chain fatty acids created by the gut microbiome. These microbes also signal serotonin, gamma-aminobutyric acid (GABA) and dopamine.⁷

This details how alterations in the microbiome, through stress, poor diet, autoimmune illness, and overuse of antibiotics impact the brain. This contributes to the susceptibility of environmental toxins and oxidative stress, resulting in neuron degradation and toxicity. The impact of ageing and genetic predisposition to neurological disorders also increases with systemic inflammation.⁴

Hormonal Influences

Activation of the sympathetic nervous system (SNS) stimulates catecholamine hormones, also encouraging pro-inflammatory cytokine release. While this can be balanced by cortisol, dysregulation contributes to inhibited immune function. Continuous excretion of catecholamines increases blood sugar and lipid levels, and increased heart rate, implicating factors in metabolic conditions, stroke, and cardiovascular disease.

Recent studies on chronic stress also associated elevated C-reactive protein (CRP) levels with increased neurological symptoms of anxiety, panic, and depression.⁸ This may be influenced by CRP binding to microglia, causing continuous overactivation.⁶

Direct implications of cellular alterations include cognitive symptoms of food aversion, fatigue, depression, anxiety, and debility. Chronic inflammation can then create ongoing behavioural alterations and overall decreased cognition.⁹

Phytotherapy Recommendations

Inflammation is designed to re-establish balance or homeostasis. When this signalling system fails to self-regulate, it can be detrimental to neurological health and overall wellbeing. Phytomedicines that can help in this response include:

Crocus sativus (saffron)
Saffron down-regulates IL-1β, IL-6, and TNF-α, and cyclo-oxygenase. Saffron also balances blood sugar, blood pressure and lipid levels.

Ginkgo biloba (ginkgo)
A cognition enhancer and neuroprotective, ginkgo also has significant antioxidant actions, supporting cellular recovery. It is particularly helpful for brain injury, concentration, and memory enhancement.

Hericium erinaceus (lion’s mane)
anxiolytic, antidepressant and cognition-enhancing actions, make lion’s mane ideal for cases of neurodegeneration, particularly regarding age and chronic illness.

Momordica charantia (bitter melon)
Bitter melon modulates the immune system by enhancing natural killer cell presence. Antibacterial and anthelmintic actions offer support for immune depletion relative to chronic stress.

Lavandula angustifolia (lavender)
Anxiolytic and antidepressant actions make lavender supportive for symptoms associated with neuron damage and cognitive decline.

Ocimum sanctum (holy basil)
An anxiolytic and neuro-protective herb, holy basil calms the CNS and HPA axis. Its tonic and adaptogen properties contribute to cardio-protective, anti-hypertensive and immune-modulating activity.

Withania somnifera (withania)
As a tonic and adaptogen, withania regulates stress and modulates the immune system. Withania also downgrades inflammatory markers and re-balances blood sugar levels.

Zingiber officinale (ginger)
Ginger’s digestive actions support stress-related conditions including dyspepsia and anxiety-induced nausea. While its pungent constituents gingerols and shogaols provide anti-inflammatory and antioxidant actions.


References

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