McEwen · European journal of pharmacology 2008 · narrative review · n=?

Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators.

Cited 1901 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and conceptual framework paper with no primary data

PubMed 18282566 · doi:10.1016/j.ejphar.2007.11.071 · record verified 2026-08-26

What was done

This narrative review synthesized the neurobiological mechanisms of acute versus chronic stress. It evaluated how stress mediators—including glucocorticoids, excitatory amino acids, brain-derived neurotrophic factor (BDNF), polysialated neural cell adhesion molecule (PSA-NCAM), and tissue plasminogen activator (tPA)—drive neural remodeling in the hippocampus, prefrontal cortex, and amygdala, and assessed how these changes connect to allostatic overload, psychiatric illness, and behavioral interventions.

What was found

The abstract reports no numerical data. It notes that acute stress drives adaptive survival responses across neural, cardiovascular, autonomic, immune, and metabolic systems, whereas chronic stress dysregulates these systems. Stress-induced morphological and chemical changes in the hippocampus, prefrontal cortex, and amygdala are described as largely reversible after weeks of stress, though whether months or years of stress cause irreversible changes remains unestablished.

Why it matters

The paper outlines the conceptual model of allostatic overload, framing stress-related brain remodeling as a target for lifestyle interventions like physical activity and social support alongside pharmacotherapy.

Limits

The abstract describes a narrative review with no primary empirical data, sample sizes, or systematic review methodology. Long-term irreversibility of human brain changes from multi-year stress remains unknown based on the provided text.

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