Does lithium poisoning induce brain injuries?—A histopathological rat study. Issue 5 (26th February 2023)

• Record Type: Journal Article
• Authors: Klein, Mathieu; Naffaa, Vanessa; Chevillard, Lucie; Risède, Patricia; Saubaméa, Bruno; Adle‐Biassette, Homa; Mégarbane, Bruno
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 132:Issue 5(2023)
• Page Start: 449
• Page End: 453
• Publication Date: 2023-02-26
• Subjects: lithium -- microscopy -- neurotoxicity -- poisoning -- SILENT; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.13847
• Languages: English
• ISSNs: 1742-7835

Abstract

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.