Combination of Dexamethasone and Aminoguanidine Reduces Secondary Damage in Compression Spinal Cord Injury
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The study was performed to investigate the effect of combination therapy with aminoguanidine (AG) and dexamethasone (DEX) on the compression spinal cord injury (SCI) in rat. Compared to the control group, the combination therapy group with AG (75 mg/kg) and DEX (0.025 mg/kg) significantly reduced the degree of (1) spinal cord edema, (2) the permeability of blood spinal cord barrier (measured by 99mTc-Albumin), (3) infiltration of neutrophils (MPO evaluation), (4) cytokines expression (tumor necrosis factor-α and interleukin-1β), and (5) apoptosis (measured by Bax and Bcl-2 expression). In addition, we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly indicated for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of SCI.
KeywordsAminoguanidine Spinal cord injury Dexamethasone
This work was supported by Special fund for scientific research of postdoctoral subjects in China, No. 20060400292, Natural Science Foundation of Liaoning Province in China, No. 20082207 and Special fund for scientific research of doctoral subjects in Liaoning Province in China, No. 20081052.
- Caldenhoven E, Liden J, Wissink S, Van de Stolpe A, Raaijmakers J, Koenderman L, Okret S, Gustafsson JA, Van der Saag PT (1995) Negative cross-talk between RelA and the glucocorticoid receptor: a possible mechanism for the antiinflammatory action of glucocorticoids. Mol Endocrinol 9:401–412. doi: 10.1210/me.9.4.401 PubMedCrossRefGoogle Scholar
- Gonzalez Deniselle MC, Gonzalez S, Piroli G, Ferrini M, Lima AE, De Nicola AF (1997) Glucocorticoid receptors and actions in the spinal cord of the wobbler mouse, a model for neurodegenerative diseases. J Steroid Biochem Mol Biol 60:205–213. doi: 10.1016/S0960-0760(96)00193-8 PubMedCrossRefGoogle Scholar
- Huang WL, George KJ, Ibba V, Liu MC, Averill S, Quartu M et al. (2007) The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. Eur J Neurol 25:362–372Google Scholar
- Joshi M, Fehlings MG (2002) Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 2. Quantitative neuroanatomical assessment and analysis of the relationships between axonal tracts, residual tissue, and locomotor recovery. J Neurotrauma 19:191–203PubMedCrossRefGoogle Scholar
- Louin G, Marchand-Verrecchia C, Palmier B, Plotkine M, Jafarian-Tehrani M (2006) Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury. Neuropharmacology 50:182–190. doi: 10.1016/j.neuropharm.2005.08.020 PubMedCrossRefGoogle Scholar
- Sharma HS, Sjöquist PO, Mohanty S, Wiklund L (2006) Post-injury treatment with a new antioxidant compound H-290/51 attenuates spinal cord trauma-induced c-fos expression, motor dysfunction, edema formation, and cell injury in the rat. Acta Neurochir Suppl (Wien) 96:322–328. doi: 10.1007/3-211-30714-1_68 CrossRefGoogle Scholar
- Zhang XY, Zhou CS, Jin AM, Tian J, Zhang H, Yao WT, Zheng G (2003) Effect of aminoguanidine on the recovery of rat hindlimb motor function after spinal cord injury. Di Yi Jun Yi Da Xue Xue Bao 23:687–689Google Scholar