Lees · Brain research. Brain research reviews 1991 · narrative review · n=?

Inhibition of sodium-potassium-ATPase: a potentially ubiquitous mechanism contributing to central nervous system neuropathology.

Cited 311 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic hypotheses without new human experimental data.

PubMed 1665097 · doi:10.1016/0165-0173(91)90011-v · record verified 2026-08-26

What was done

This paper is a narrative review presenting a mechanistic hypothesis on how reduced or inhibited Na+/K+-ATPase activity contributes to neuronal damage in central nervous system disorders, including ischemia, hypoglycemia, epilepsy, and excitotoxin exposure.

What was found

The abstract reports no quantitative data or numerical findings. It outlines qualitative mechanistic pathways: Na+/K+-ATPase inhibition collapses the transmembrane sodium gradient, which blocks glutamate reuptake and stimulates neurotransmitter release; membrane depolarization removes the magnesium block from NMDA receptors and opens voltage-gated calcium channels; failure of sodium-calcium exchange leads to toxic intracellular calcium accumulation; and sodium retention causes osmotic swelling and cell lysis.

Why it matters

It provides a unifying pathophysiological framework linking metabolic failure and impaired ion transport to glutamate-mediated excitotoxic cell death across acute neurological insults.

Limits

The abstract describes a theoretical framework and narrative synthesis rather than a systematic review or primary clinical trial. No sample sizes, quantitative estimates, or empirical outcome data are provided.

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