Sapolsky · Stress (Amsterdam, Netherlands) 1996 · narrative review · n=?

Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion.

Cited 743 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic and preclinical literature without systematic search or original human data.

PubMed 9807058 · doi:10.3109/10253899609001092 · record verified 2026-08-29

What was done

Narrative review synthesizing literature on the deleterious effects of stress-induced glucocorticoids (GCs) on the brain, particularly the hippocampus. The paper outlines three phenotypic outcomes of GC exposure (atrophy, neurotoxicity, and neuroendangerment) and assesses five mechanistic themes underlying these actions.

What was found

The abstract reports no numerical data. It notes that GC actions include reversible dendritic atrophy following weeks of exposure, neuronal cell death following months of exposure, and neuroendangerment during acute insults such as stroke or seizure. It identifies five contributing mechanisms: metabolic vulnerability from inhibited glucose uptake, exacerbation of glutamate excess and calcium/oxygen radical cascades, impaired neuronal defenses, disrupted neurotrophin mobilization, and damaging electrophysiological alterations.

Why it matters

This review updates earlier models of stress-induced neurodegeneration by demonstrating that glucocorticoids damage neurons through multiple interacting cellular pathways beyond simple metabolic and energetic vulnerability.

Limits

As a narrative review, it lacks systematic search criteria, quality appraisal, and meta-analytic synthesis. No quantitative effect sizes or sample sizes are reported in the abstract, and the underlying evidence relies heavily on preclinical animal and in vitro models.

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