Lithium and neuroprotection

Neuroprotection can be defined as medical prophylactic and therapeutic intervention aimed at neuronal tissue and function. Hardly any concept of neuroprotection has been convincingly efficient in man thus far. Lithium has been used for the treatment of manic depressive illness for 50 years, but the mechanisms by which this cation exerts its beneficial effects are not yet clear. The last five years several studies have indicated that lithium mediates neuroprotection. In this essay we review the mechanisms by which lithium might exert its neuroprotective effects. We show that lithium has been demonstrated to modulate excitatory and inhibitory synapses and adjust signalling activities regulating second messengers, transcription factors and gene expression in vitro and in vivo. Important targets of action are Bcl-2, GSK-3 and glutamate neurotransmission. Lithium protects against diverse insults in animal models of disease and enhances neurogenesis in vitro and in rodent brains. It has also been shown that lithium increases grey-matter volume in bipolar patients in vivo and post mortem, and increases N-acetyl-aspartate, a putative marker of neuronal viability, in bipolar patients and healthy volunteers. Thus far neuroprotective effects of lithium in man have not been well established. Further elucidation requires clinical studies. We end our essay by outlining possible directions of research