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A new avenue for lithium: intervention in traumatic brain injury.
ACS Chem Neurosci. 2014 Jun 18; 5(6):422-33.AC

Abstract

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.

Authors+Show Affiliations

†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.No affiliation info available†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.†Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1363, Bethesda, Maryland 20892-1363, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

24697257

Citation

Leeds, Peter R., et al. "A New Avenue for Lithium: Intervention in Traumatic Brain Injury." ACS Chemical Neuroscience, vol. 5, no. 6, 2014, pp. 422-33.
Leeds PR, Yu F, Wang Z, et al. A new avenue for lithium: intervention in traumatic brain injury. ACS Chem Neurosci. 2014;5(6):422-33.
Leeds, P. R., Yu, F., Wang, Z., Chiu, C. T., Zhang, Y., Leng, Y., Linares, G. R., & Chuang, D. M. (2014). A new avenue for lithium: intervention in traumatic brain injury. ACS Chemical Neuroscience, 5(6), 422-33. https://doi.org/10.1021/cn500040g
Leeds PR, et al. A New Avenue for Lithium: Intervention in Traumatic Brain Injury. ACS Chem Neurosci. 2014 Jun 18;5(6):422-33. PubMed PMID: 24697257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new avenue for lithium: intervention in traumatic brain injury. AU - Leeds,Peter R, AU - Yu,Fengshan, AU - Wang,Zhifei, AU - Chiu,Chi-Tso, AU - Zhang,Yumin, AU - Leng,Yan, AU - Linares,Gabriel R, AU - Chuang,De-Maw, Y1 - 2014/04/11/ PY - 2014/4/5/entrez PY - 2014/4/5/pubmed PY - 2015/10/9/medline KW - Anti-inflammation KW - GSK-3 (glycogen synthase kinase-3) inhibitor KW - TBI (traumatic brain injury) KW - behavioral deficits and cognitive improvements KW - combined therapy treatment KW - controlled cortical impact KW - functional recovery KW - lithium KW - mood stabilizer KW - neuroprotection KW - neuroregeneration KW - preclinical model SP - 422 EP - 33 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 5 IS - 6 N2 - 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. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/24697257/A_new_avenue_for_lithium:_intervention_in_traumatic_brain_injury_ L2 - https://dx.doi.org/10.1021/cn500040g DB - PRIME DP - Unbound Medicine ER -