Does lithium poisoning induce brain injuries?-A histopathological rat study

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.

Automated summary

Due to a narrow therapeutic index, prolonged lithium treatment and overdose may lead to reversible neurotoxicity. However, in rare severe poisonings, irreversible brain injuries have been reported. This study aimed to investigate the histopathological consequences of lithium exposure in rat models and found that no brain lesion or significant difference in neuron and astrocyte counts were observed between lithium-treated rats and controls, suggesting that lithium-induced neurotoxicity is reversible and brain injury is not a common feature of toxicity.