2015, Number 4
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Arch Neurocien 2015; 20 (4)
Phenobarbital administered alone or in combination with dapsone inhibits apoptosis and improves motor function after spinal cord injury in rats
Díaz-Ruiz A, Méndez-Armenta M, Nava-Ruiz C, Garduño C, Santander I, Ruiz A, Ríos C
Language: Spanish
References: 31
Page: 240-246
PDF size: 142.96 Kb.
ABSTRACT
Traumatic spinal cord injury (SCI) is a health problem that affects the working age population (20-45 years) and
there is no effective treatment. Our group has demonstrated that phenobarbital (FB) and dapsone (DDS) have
neuroprotective effects in models of stroke and excitotoxicity.
Objective: to evaluate the therapeutic effect of FB
administered alone or in combination with DDS during the acute stage after SCI by measuring the activity of Caspase-
3 and motor functional recovery.
Material and methods: female rats (250 g) were used, the groups were: laminectomy
(control), SCI, treated with FB or DDS, alone or in combination, and all them sacrificed 72 h after surgery to
measure the activity of caspase-3, motor recovery was evaluated for 2 months.
Results: the values of caspase-3
activities showed an increase by effect of lesion and were diminished in all animals that received treatments
administered alone or in combination. Likewise, animals treated with FB alone or in combination with DDS had the
best functional performance, being the most effective the combined therapy with an increase of 135% over the lesion group.
Conclusions: the results obtained demonstrated that both drugs provide therapeutic benefits by reducing
apoptosis and promoting functional recovery of the animals. Therefore, the findings of this study may have value as
an effective pharmacological strategy in clinical practice.
REFERENCES
Lee BB, Cripps RA, Fitzharris M, Wing PC. The global map for traumatic spinal cord injur y epidemiology: update 2011, global incidence rate. Spinal Cord 2014; 52(2):110-6.
Torres S, Salgado-Ceballos H, Guizar-Sahagún G, Torres JL. Deleterious versus neuroprotective ef fect of metabolic inhibition after traumatic spinal cord injury. Spinal Cord 2009; 47(10):745-50.
Park E, Velumian AA, Fehlings MG. The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma 2004; 21(6):754-74.
Diaz-Ruiz A, Rios C, Duarte I, Correa D, Guizar-Sahagun G, Grijalva I, et al. Lipid peroxidation inhibition in spinal cord injur y: cyclosporin-A vs methylprednisolone. Neuroreport 2000; 11(8):1765-7.
Titsworth WL, Liu NK, Xu XM. Role of secretory phospholipase A2 in CNS inflammation: implications in traumatic spinal cord injury. CNS Neurol Disord Drug Targets 2008; 7(3):254-69.
Springer JE. Apoptotic cell death following traumatic injury to the central ner vous system. J Biochem Mol Biol 2002; 35(1):94-105.
Precht TA, Phelps RA, Linseman DA, Butts BD, Le SS, Laessig TA, et al. The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis. Cell Death Differ 2005; 12(3):255-65.
Yip PK, Malaspina A. Spinal cord trauma and the molecular point of no return. Mol Neurodegener 2012; 8(7):6.
Trinka E. What is the relative value of the standard anticonvulsants: Phenytoin and fosphenytoin, phenobarbital, valproate, and levetiracetam? Epilepsia 2009; 50 Suppl 12:40-3.
Wallace AE, Kline AE, Montañez S, Hernandez TD. Impact of the novel anti-convulsant vigabatrin on functional recovery following brain lesion. Restor Neurol Neurosci 1999; 14(1): 35-45.
Díaz-Ruiz A, Zavala C, Montes S, Ortiz-Plata A, Salgado- Ceballos H. Antioxidant, antiinflammatory and antiapoptotic effects of dapsone in a model of brain ischemia/reperfusion in rats. J Neurosci Res 2008; 86(15):3410-9.
Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch Dermatol Res 2014; 306(2):103-24.
Ríos C, Nader-Kawachi J, Rodriguez-Payán AJ, Nava-Ruiz C. Neuroprotective effect of dapsone in an occlusive model of focal ischemia in rats. Brain Res 2004; 999(2):212-5.
Díaz-Ruiz A, Salgado-Ceballos H, Montes S, Guizar-Sahagún G. Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury. J Neurosci Res 2011; 89(3):373-80.
Sudha S, Lakshmana MK, Pradhan N. Phenobarbital in the anticonvulsant dose range does not impair learning and memory or alter brain AChE activity or monoamine levels. Pharmacol Biochem Behav 1996; 54(3):633-8.
Diaz-Ruiz A, Mendez-Armenta M, Galván-Arzate S, Manjarrez J, Nava-Ruiz C. Antioxidant, anticonvulsive and neuroprotective effects of dapsone and phenobarbital against kainic acidinduced damage in rats. Neurochem Res 2013; 38(9):1819- 27.
Ríos C, Orozco-Suarez S, Salgado-Ceballos H, Mendez-Armenta M. Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats. Neurochem Res 2015; 40(6):1243-51.
Lowry OH, Rosebrouugh NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1):265-75.
Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device vs transection. Exp Neurol 1996; 139: 244-56.
Takagi T, Takayasu M, Mizuno M, Yoshimoto M, Yoshida J. Caspase activation in neuronal and glial apoptosis following spinal cord injur y in mice. Neurol Med Chir (Tokyo) 2003; 43(1):20-9.
Knoblatch SM, Huang X, VanGelderen J, Calva-Cerqueira D, Faden AI. Selective caspase activation may contribute to neurological dysfunction after experimental spinal cord trauma. J Neurosci Res 2005; 80(3):369-80.
Ling X, Bao F, Qian H, Liu D. The temporal and spatial profiles of cell loss following experimental spinal cord injury: effect of antioxidant therapy on cell death and functional recovery. BMC Neurosci 2013; 18;14:146.
Beattie MS, Hermann GE, Rogers RC, Bresnahan JC. Cell death in models of spinal cord injury. Prog Brain Res 2002;137:37- 47.
Baumgartner HK, Gerasimenko JV, Thorne C, Ferdek P. Calcium elevation in mitochondria is the main Ca2+ requirement for mitochondrial permeability transition pore (mPTP) opening. J Biol Chem 2009; 284(31):20796-803.
Bao F, Liu D. Hydroxyl radicals generated in the rat spinal cord at the level produced by impact injury induce cell death by necrosis and apoptosis: protection by a metalloporphyrin. Neuroscience 2004; 126(2):285-95.
Ren Y, Young W. Managing inflammation after spinal cord injury through manipulation of macrophage function. Neural Plast 2013; 945034.
Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005; 5(12):953-64.
Barks JD, Liu YQ, Shangguan Y, Silverstein FS. Phenobarbital augments hypothermic neuroprotection. Pediatr Res 2010; 67(5):532-7.
Sutula T, Cavazos J, Golarai G. Alteration of long-lasting structural and functional ef fects of kainic acid in the hippocampus by brief treatment with phenobarbital. J Neurosci 1992; 12: 4173-87.
Rekling C. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation, Neurosci Lett 2003; 335: 167-70.
Rodríguez E, Méndez-Armenta M, Villeda-Hernández J, Galván-Arzate S. Dapsone prevents morphological lesions and lipid peroxidation induced by quinolinic acid in rat corpus striatum. Toxicology 1999; 139 (1-2):111-8.