Is Lithium a Potential Aid in Traumatic Brain Injury?

Lithium carbonate serves as a primary treatment option in the treatment of mania and bipolar affective disorder.  An elemental metal, lithium has atomic number 3 in the periodic table of elements.

The mechanism of action for lithium carbonate in bipolar disorder is unclear.  Some of the proposed mechanisms for lithium in the central nervous system include:

• alteration of the neurotransmitter glutamate (affected by other drugs linked to therapeutic effect in bipolar disorder, i.e. sodium valproate and lamotrigine)
• alteration in gene expression
• inactivation of the GSK-3B (glycogen synthase kinase) enzyme known to be involved in circadian clock regulation
• interaction with the NO (nitrous oxide) signalling pathway

Inhibition of the GSK-3B enzyme has been shown to have potential beneficial effects in stimulating neuroplasticity as it is associated with enhanced expression of brain-derived neurotrophic factor (BDNF).  Fengshan Yu and colleagues at NIH and the University of Health Sciences have recently explored the effect of lithium on traumatic brain injury using a mouse model.

In their experiment, mice received doses of lithium chloride ranging form 1.0 to 5.0 mEq/kg dose of lithium or placebo following a controlled episode of brain trauma under anesthesia.  Doses were repeated daily for three days.

Brain injury response to lithium treatment was monitoring using neuropathological techniques as well as behavior and motor coordination tests.  The key results of the study include:

• Lithium chloride at 1.5 to 3.0 mEq/kg reduced brain lesion volume compared to control
• Lithium chloride reduced post-trauma related anxiety behavior during the outcome monitoring
• Lithium chloride reduced breakdown of the blood-brain barrior
• Short-term and long-term motor coordination was better in the lithium group

The authors note that their study suggests the neuroprotective effect of lithium administration following traumatic brain injury in the mouse model appears related to a GSK-3B mechanism.  The study timed lithium administration to 3 hours after the trauma providing a realistic model for a trial in human clinical scenarios.  They conclude "Our results that demonstrate its (lithium chloride) benefits in the mouse model pave the way for early clinical trials as potential treatment for TBI (traumatic brain injury) patients.

CT of traumatic brain injury showing cerebral contusion, cerebral hemmorhage, subdural hematoma and skull fracture from Wikipedia Creative Commons. Source: Rehman T, Ali R, Tawil I, Yonas H (2008). "Rapid progression of traumatic bifrontal contusions to transtentorial herniation: A case report". Cases journal 1 (1): 203. doi:10.1186/1757-1626-1-203. PMID 18831756. http://www.casesjournal.com/content/1/1/203


Yu F, Wang Z, Tchantchou F, Chiu CT, Zhang Y, & Chuang DM (2011). Lithium ameliorates neurodegeneration, suppresses neuroinflammation, and improves behavioral performance in a mouse model of traumatic brain injury. Journal of neurotrauma PMID: 21895523