Citation

Klein M, Naffaa V, Chevillard L, Risède P, Saubaméa B, Adle-Biassette H, Megarbane B. Basic Clin. Pharmacol. Toxicol. 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Nordic Pharmacological Society, Publisher John Wiley and Sons)

DOI

10.1111/bcpt.13847

PMID

36808477

Abstract

Due to a narrow therapeutic index, prolonged lithium treatment and overdose may result in neurotoxicity. Neurotoxicity is deemed reversible with lithium clearance. However, echoing the report of syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) in rare severe poisonings, lithium-induced histopathological brain injuries including extensive neuronal vacuolization, spongiosis, and ageing-like neurodegenerative changes were described in the rat following acute toxic and pharmacological exposure. We aimed to investigate the histopathological consequences of lithium exposure in rat models mimicking prolonged treatment and all three patterns of acute, acute-on-chronic, and chronic poisonings observed in humans. We performed histopathology and immunostaining-based analyses using optic microscopy of brains obtained from male Sprague-Dawley rats randomly assigned to lithium or saline (controls) and treated according to the therapeutic or to the three poisoning models. No lesion was observed in any brain structure in any of the models. Neuron and astrocyte counts did not differ significantly between lithium-treated rats and controls. Our findings support that lithium-induced neurotoxicity is reversible and brain injury not a common feature of toxicity.

Language: en

Keywords

Poisoning; Microscopy; Lithium; Neurotoxicity; SILENT