Dilip KC, M.D., Steven Lippmann, M.D.

We all know that lithium has important pharmacological properties (1). Most famously, it can provide mood stabilization in patients with bipolar disorders (2). Lithium reduces the risk of suicide in individuals with depression (3). Indeed, it may be helpful in mitigating depressions and possibly in other psychiatric disorders. It may also have a possible neuroprotective role in treating patients with traumatic brain injury and certain neurological conditions, like Huntington’s disease (4-6) 

Also, lithium has great utility in non-medical areas, such as a prominent value in the manufacture of new, highly efficient batteries (7). It even is used in building aircraft (8).

Research in animals reveals a potential role of lithium in reversing the neuronal dysfunction caused due to compression by brain tumors (9). There is a suggestion that lithium might improve the prognosis of patients with brain tumors (10,11). Something new?

Researchers experimented with the negative aspects of compression on brain function by the presence of central nervous system tumors. Deformed cortical tissues evidence reduced vascular perfusion and cellular distress within neurons. Mice experiencing cortical compression exhibited abnormal movement and coordination skills.

Because of questions about neuroprotection, the investigators studied four medicines in mice with brain tumors that had induced neurological dysfunction (9). Lithium, valproic acid, dexamethasone, and necrostatin were the study drugs. Lithium appeared to mitigate the damaging effects of the solid mass stress caused by brain tumors. The lithium-treated mice were the only ones reported to have displayed less impairment of motor and cerebellar function.

Maybe we are on to something new? Perhaps, lithium might provide some neuroprotective benefit to patients with brain tumors that compress surrounding tissues (9-11). However, this is an animal-based, very preliminary study, not tested in humans. Research into possible neuroprotective benefits induced by lithium might be better defined in the future.

References

1. Maletzky BM, Shore JH. Lithium treatment for psychiatric disorders. West J Med, 1978. 128(6): 488-498.
2. Machado-Vieira R, Manji HK, Zarate CA. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord, 2009. 11 (Suppl 2): 92-109.
3. Lewitzka U, Severus E, Bauer R, et al. The suicide prevention effect of lithium: more than 20 years of evidence-a narrative review. Int J Bipolar Disord, 2015. 3(1): 32.
4. Diaz-Arrastia R, Kochanek PM, Bergold P, et al. Pharmacotherapy of traumatic brain injury: state of the science and the road forward: report of the Department of Defense Neurotrauma Pharmacology Workgroup. J Neurotrauma, 2014. 31(2): 135-158.
5. Yu F, Wang Z, Tanaka M, et al. Posttrauma cotreatment with lithium and valproate: reduction of lesion volume, attenuation of blood-brain barrier disruption, and improvement in motor coordination in mice with traumatic brain injury. Journal of neurosurgery, 2013. 119(3): 766-773.
6. Wu S, Zheng SD, Huang HL, et al. Lithium down-regulates histone deacetylase 1 (HDAC1) and induces degradation of mutant huntingtin. J Biol Chem, 2013. 288(49): 35500-35510.
7. Goonan TG. 2012, Lithium use in batteries: U.S. Geological Survey Circular 1371, 14 p., available at https://pubs.usgs.gov/circ/1371. New England Journal of Medicine, 1993. 328(25): 1807-1811.
8. Khokhlatova LB, Kolobnev NI, Oglodkov MS, et al. Aluminum-lithium alloys for aircraft building. Metallurgist, 2012. 56(5): 336-341.
9. Seano G, Nia HT, Emblem KE, et al. Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. Nature Biomedical Engineering, 2019(included ahead of publication Feb 18 2019).
10. Nowicki MO, Dmitrieva N, Stein AM, et al. Lithium inhibits invasion of glioma cells; possible involvement of glycogen synthase kinase-3. Neuro-Oncology, 2008. 10(5): 690-699.
11. Maeng YS, Lee R, Lee B, et al. Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells. Sci Rep, 2016. 6: 20739.