Effects of lithium chloride and methylprednisolone on experimental spinal cord injury

Abstract

Objective. Antioxidant effects of lithium chloride (LiCl) and methylprednisolone were investigated in an experimental spinal cord injury. Methods. Spinal cord injury was performed by cerebral vascular clip with a closing force of 40 g; the duration of epidural compression was 30 seconds after T9-11 total laminectomy in the rat spine. The study was conducted in 4 groups. Group 1: sham (n=8), group 2: 0.9% saline (n=8), group 3: LiCl (n=8), group 4: methylprednisolone (n=8). Ketamine (60 mg/kg) and 2% xylazine (5 mg/kg) were used intraperitoneally as anesthesia protocol for the groups. The rats were sacrificed 24 hours after the injury and blood samples were taken. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) level were analyzed. Results. Median (q1-q3) levels of TAS, TOS, MDA and TNF-α were statistically analyzed for the study groups. The TAS values of LiCl yielded statistically significant differences compared with group 1, 2 and 4 (p<0.05). The MDA values of LiCl and methylprednisolone groups were found to significantly differ between the sham and saline groups (p<0.05). There were no statistical differences between the study groups for the TNF-α and TOS values (p>0.05). Conclusion. LiCl seems to be an effective drug for experimental spinal cord injuries. 

 

Keywords

• Spinal cord injury
• experimental
• treatment
• lithium chloride
• methylprednisolone

References

1. Findling RL, Kafantaris V, Pavuluri M, McNamara NK, McClellan J, Frazier JA, et al. Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder. J Child Adolesc Psychopharmacol 2011;21:195-205.
2. Licht RW. Lithium: still a major option in the management of bipolar disorder. CNS Neurosci Ther 2012;18:219-26.
3. Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta 2012;1822:675-84.
4. Werndle MC, Zoumprouli A, Sedgwick P, Papadopoulos MC. Variability in the treatment of acute spinal cord injury in the United Kingdom: results of a national survey. J Neurotrauma 2012;29:880-8.
5. Whittaker MT, Zai LJ, Lee HJ, Pajoohesh-Ganji A, Wu J, Sharp A. et al. GGF2 (Nrg1-β3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury. Glia 2012;60:281-94.
6. Nonaka S, Hough CJ, Chuang DM. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. Proc Natl Acad Sci U S A 1998;95:2642-7.
7. Ohkawa H, Ohishi N, Yagi K. Assay For Lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
8. Bracken MB. Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2012;18:1:CD001046.

9. Lee JM, Yan P, Xiao Q, Chen S, Lee KY, Hsu CY, et al. Methylprednisolone protects oligodendrocytes but not neurons after spinal cord injury. J Neurosci 2008;28:3141-9.
10. Miller SM. Methylprednisolone in acute spinal cord injury: a tarnished standard. J Neurosurg Anesthesiol 2008;20:140-2.
11. Xu J, Chen S, Chen H, Xiao Q, Hsu CY, Michael D, et al. STAT5 mediates antiapoptotic effects of methylprednisolone on oligodendrocytes. J Neurosci 2009;29:2022-6.
12. Small JG, Klapper MH, Malloy FW, Steadman TM. Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder. J Clin Psychopharmacol 2003;23:223-8.
13. Boku S, Nakagawa S, Masuda T, Nishikawa H, Kato A, Kitaichi Y, et al. Glucocorticoids and lithium reciprocally regulate the proliferation of adult dentate gyrus-derived neural precursor cells through GSK-3beta and beta-catenin/TCF pathway. Neuropsychopharmacology 2009;34:805-15.
14. Young W. Review of lithium effects on brain and blood. Cell Transplant 2009;18:951-75.
15. Dill J, Wang H, Zhou F, Li S. Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS. J Neurosci 2008;28:8914-28.
16. Bailly-Maitre B, de Sousa G, Boulukos K, Gugenheim J, Rahmani R. Dexamethasone inhibits spontaneous apoptosis in primary cultures of human and rat hepatocytes via Bcl-2 and Bcl-xL induction. Cell Death Differ 2001;8:279-88.
17. Lindsten T, Zong WX, Thompson CB. Defining the role of the Bcl-2 family of proteins in the nervous system. Neuroscientist 2005;11:10-5.
18. Nesic-Taylor O, Cittelly D, Ye Z, Xu GY, Unabia G, Lee JC, et al. Exogenous Bcl-Xl fusion protein spares neurons after spinal cord injury. J Neurosci Res 2005;79:628-37.
19. Cittelly DM, Nesic-Taylor O, Perez-Polo JR. Phosphorylation of Bcl-xL after spinal cord injury. J Neurosci Res 2007;85:1894-911.
20. Mohn AR, Gainetdinov RR, Caron MG, Koller BH. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 1999;98:427-36.
21. Nieoullon A, Kerkerian L, Dusticier N. Inhibitory effects of dopamine on high affinity glutamate uptake from rat striatum. Life Sci 1982;30:1165-72.
22. Nieoullon A, Kerkerian L, Dusticier N. Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum. Neurosci Lett 1983;43:191-6.
23. Carlsson A, Hansson LO, Waters N, Carlsson ML. Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic implications. Life Sci 1997;61:75-94.
24. Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol 2002;42:165-79.
25. Javitt DC. Glutamatergic theories of schizophrenia. Isr J Psychiatry Relat Sci 2010;47:4-16.
26. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 1995;52:998-1007.