PMID- 24697257 OWN - NLM STAT- MEDLINE DCOM- 20151008 LR - 20211021 IS - 1948-7193 (Electronic) IS - 1948-7193 (Print) IS - 1948-7193 (Linking) VI - 5 IP - 6 DP - 2014 Jun 18 TI - A new avenue for lithium: intervention in traumatic brain injury. PG - 422-33 LID - 10.1021/cn500040g [doi] AB - 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-beta (Abeta), 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. FAU - Leeds, Peter R AU - Leeds PR AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. FAU - Yu, Fengshan AU - Yu F AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. FAU - Wang, Zhifei AU - Wang Z AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. FAU - Chiu, Chi-Tso AU - Chiu CT AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. FAU - Zhang, Yumin AU - Zhang Y FAU - Leng, Yan AU - Leng Y AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. FAU - Linares, Gabriel R AU - Linares GR AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. FAU - Chuang, De-Maw AU - Chuang DM AD - daggerMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States. LA - eng GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Review DEP - 20140411 PL - United States TA - ACS Chem Neurosci JT - ACS chemical neuroscience JID - 101525337 RN - 0 (Lithium Compounds) RN - 0 (Neuroprotective Agents) SB - IM MH - Animals MH - Brain Injuries/*drug therapy/physiopathology MH - Humans MH - Lithium Compounds/*pharmacology/therapeutic use MH - Neuroprotective Agents/*pharmacology/therapeutic use PMC - PMC4063503 OTO - NOTNLM OT - Anti-inflammation OT - GSK-3 (glycogen synthase kinase-3) inhibitor OT - TBI (traumatic brain injury) OT - behavioral deficits and cognitive improvements OT - combined therapy treatment OT - controlled cortical impact OT - functional recovery OT - lithium OT - mood stabilizer OT - neuroprotection OT - neuroregeneration OT - preclinical model EDAT- 2014/04/05 06:00 MHDA- 2015/10/09 06:00 PMCR- 2015/06/18 CRDT- 2014/04/05 06:00 PHST- 2014/04/05 06:00 [entrez] PHST- 2014/04/05 06:00 [pubmed] PHST- 2015/10/09 06:00 [medline] PHST- 2015/06/18 00:00 [pmc-release] AID - 10.1021/cn500040g [doi] PST - ppublish SO - ACS Chem Neurosci. 2014 Jun 18;5(6):422-33. doi: 10.1021/cn500040g. Epub 2014 Apr 11.