Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial

Yang, Mingliang; Li, J J; So, Kwok-Fai; Chen, J Y H; Cheng, Wendy; Wu, Jie; Wang, Z M; Gao, Fang; Young, Wise

doi:10.1038/sc.2011.126

Cited by 67 publications

(43 citation statements)

References 41 publications

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“…25 Another neuroregenerative agent, lithium carbonate, was investigated, but it did not improve the neurological outcome in patients with SCI. 26 Many studies have shown the effects of exercise training on neuronal plasticity. Exercise improved gait and led to neurological recovery, 27 probably by enabling the intrinsic neuronal circuitry.…”

Section: Discussionmentioning

confidence: 99%

Effects of antidepressant and treadmill gait training on recovery from spinal cord injury in rats

et al. 2013

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Study design: Experimental, controlled, animal study. Objectives: To evaluate the influences of antidepressant treatment, treadmill gait training and a combination of these therapies in rats with experimental, acute spinal cord injury (SCI). Setting: Brazil. Methods: 48 Wistar rats were given standardized SCI; rats were then randomly assigned to four treatment groups: (1) motor rehabilitation therapy for 1 hour daily (gait training); (2) daily treatment with the antidepressant, fluoxetine (0.3 ml per 100 g intraperitoneally), beginning 24 h after the trauma; (3) combined fluoxetine treatment and gait training, or (4) untreated (controls). Neurological recovery was tested with the Basso, Beattie and Bresnahan (BBB) scale at 2, 7, 14, 21, 28 ,35 and 42 days after injury. Moreover, on day 42, all rats underwent a motor-evoked potential test (MEP); then, after euthanasia, histopathological evaluation was conducted in the area of SCI. Results: Based on the BBB scale, the combined treatment group showed significantly greater improvement compared with the other three groups, from the 14th to the 42nd day of observation. The MEP revealed that all treated groups showed significant improvement compared with the control group (Po0.02 for latency and Po0.01 for amplitude). Conclusion: Our results indicated that a combination of antidepressant and treadmill gait training was superior to either treatment alone for improving functional deficits in rats with experimental, acute SCI.

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Section: Discussionmentioning

confidence: 99%

Effects of antidepressant and treadmill gait training on recovery from spinal cord injury in rats

et al. 2013

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“…GSK-3β inhibitors, particularly the clinical drug lithium, have been reported to be beneficial after CNS injuries. Lithium has been studied in phase I/II clinical trials to evaluate its efficacy on chronic SCI patients (Yang et al, 2012). …”

Section: Cspg Inhibition and Axon Regenerationmentioning

confidence: 99%

Molecular mechanisms of scar-sourced axon growth inhibitors

Ohtake

2015

Brain Research

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Astrogliosis is a defense response of the CNS to minimize primary damage and to repair injured tissues, but it ultimately generates harmful effects by upregulating inhibitory molecules to suppress neuronal elongation and forming potent barriers to axon regeneration. Chondroitin sulfate proteoglycans (CSPGs) are highly expressed by reactive scars and are potent contributors to the non-permissive environment in mature CNS. Surmounting strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. Currently, enzymatic digestion of CSPGs with locally applied chondroitinase ABC is the main in vivo approach to overcome scar inhibition, but several disadvantages may prevent using this bacterial enzyme as a therapeutic option for patients. A better understanding of molecular mechanisms underlying CSPG function may facilitate development of new effective therapies to overcome scar-mediated inhibition. Previous studies support that CSPGs act by non-specifically hindering the binding of matrix molecules to their cell surface receptors through steric interactions, but two members of the leukocyte common antigen related (LAR) phosphatase subfamily, protein tyrosine phosphatase σ and LAR, are functional receptors that bind CSPGs with high affinity and mediate CSPG inhibition. CSPGs may also act by binding two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3. Thus, CSPGs inhibit axon growth through multiple mechanisms, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries.

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“…HP184, a sodium/potassium channel blocker has been tested in a phase 2 clinical trial, but no official data have been released (NCT00093275). Lithium has been shown to act as a neuroregenerative agent in animal models and was tested in phase 1 and 2 clinical trials (NCT00431171, NCT00750061), but no neurological benefits were observed [125]. Notwithstanding the series of failed clinical trials, there are many ongoing trials that provide patients with some hope for novel treatment options [126].…”

Section: Clinical Trials In the Spinal Cordmentioning

confidence: 98%