COMPENDIUM ON FUNCTIONAL MEDICINE - Flipbook - Page 596
Intestinal hyperpermeability often precedes BBB dysfunction
through the gut-brain axis [77, 78]
Post-Infection Syndromes
Neurological symptoms following infections like COVID-19 may
involve persistent BBB disruption [79, 80]
Psychiatric Disorders
Emerging evidence links BBB dysfunction to conditions like
schizophrenia, bipolar disorder, and major depression [81, 82]
Pathophysiology: How Blood-Brain Barrier Breakdown Drives
Disease
When the BBB is compromised, a cascade of pathological events
unfolds that can lead to progressive neurological dysfunction:
Inflammatory Cascade Initiation
Entry of peripheral immune cells and inflammatory mediators
activates microglia and astrocytes, initiating neuroinflammatory
signaling [83, 84]
Oxidative and Nitrosative Stress
Reactive oxygen and nitrogen species damage neurons and
further impair BBB function in a vicious cycle [85, 86]
Excitotoxicity
Altered ion homeostasis and glutamate regulation lead to
excitotoxic neuronal injury [87, 88]
Protein Misfolding and Aggregation
BBB dysfunction contributes to impaired clearance and
accumulation of neurotoxic proteins like amyloid-ยด and tau [89,
90]
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