A New Avenue for Lithium: Intervention in TraumaticBrain Injury

摘要

Traumatic brain injury (TBI) is a leading cause of disability and death from trauma to central nervous system (CNS) tissues. For patients who survive the initial injury, TBI can lead to neurodegeneration as well as cognitive and motor deficits, and is even a risk factor for the future development of neurodegenerative disorders such as Alzheimer’s disease. Preclinical studies of multiple neuropathological and neurodegenerative disorders have shown that lithium, which is primarily used to treat bipolar disorder, has considerable neuroprotective effects. Indeed, emerging evidence now suggests that lithium can also mitigate neurological deficits incurred from TBI. Lithium exerts neuroprotective effects and stimulates neurogenesis via multiple signaling pathways; it inhibits glycogen synthase kinase-3 (GSK-3), upregulates neurotrophins and growth factors (e.g., brain-derived neurotrophic factor (BDNF)), modulates inflammatory molecules, upregulates neuroprotective factors (e.g., B-cell lymphoma-2 (Bcl-2), heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. In variousexperimental TBI paradigms, lithium has been shown to reduce neuronaldeath, microglial activation, cyclooxygenase-2 induction, amyloid-β(Aβ), and hyperphosphorylated tau levels, to preserve blood-brainbarrier integrity, to mitigate neurological deficits and psychiatricdisturbance, and to improve learning and memory outcome. Given thatlithium exerts multiple therapeutic effects across an array of CNSdisorders, including promising results in preclinical models of TBI,additional clinical research is clearly warranted to determine itstherapeutic attributes for combating TBI. Here, we review lithium’sexciting potential in ameliorating physiological as well as cognitivedeficits induced by TBI.