A new avenue for lithium: intervention in traumatic brain injury.
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 various experimental TBI paradigms, lithium has been shown to reduce neuronal death, microglial activation, cyclooxygenase-2 induction, amyloid-β (Aβ), and hyperphosphorylated tau levels, to preserve blood-brain barrier integrity, to mitigate neurological deficits and psychiatric disturbance, and to improve learning and memory outcome. Given that lithium exerts multiple therapeutic effects across an array of CNS disorders, including promising results in preclinical models of TBI, additional clinical research is clearly warranted to determine its therapeutic attributes for combating TBI. Here, we review lithium's exciting potential in ameliorating physiological as well as cognitive deficits induced by TBI.
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
Peter R
PR
Leeds
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
Fengshan
F
Yu
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
Zhifei
Z
Wang
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
Chi-Tso
CT
Chiu
Yumin
Y
Zhang
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
Yan
Y
Leng
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
Gabriel R
GR
Linares
†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.
De-Maw
DM
Chuang
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use
D018020:Lithium Compounds; D018696:Neuroprotective Agents
Anti-inflammation; GSK-3 (glycogen synthase kinase-3) inhibitor; TBI (traumatic brain injury); behavioral deficits and cognitive improvements; combined therapy treatment; controlled cortical impact; functional recovery; lithium; mood stabilizer; neuroprotection; neuroregeneration; preclinical model