Neuroprotective effects of uric acid on axotomized spinal motoneurons in neonate rats

authors:

avatar Alireza Delshad , * , avatar Mohammad Reza Jalali Nadoushan , avatar Fatemeh Ghafoori Mehr

Koomesh: Vol.17, issue 3; 772-778
published online: September 28, 2016
article type: Research Article
received: January 01, 2015
accepted: August 08, 2015

how to cite: Delshad A, Jalali Nadoushan M R, Ghafoori Mehr F. Neuroprotective effects of uric acid on axotomized spinal motoneurons in neonate rats. koomesh. 2016;17(3):e151228. 

Abstract

Introduction: Recently the neuroprotective role of uric acid (UA), as a natural biochemical substance, in neurodegenerative diseases has been proposed. Due to the critical role of apoptosis in many diseases of the nervous system, the present study was designed to investigate the anti-apoptotic effect of UA on motor neurons of the ventral spinal horn in neonate rats. Materials and Methods: Two-day-old rat neonates (n=10) were subdivided into experimental and control groups. In both groups, right sciatic nerve was transected. Experimental neonates were immediately treated with 10mg/kg UA intraperitoneally, while the control’s wound was closed without treatment. Five days after axotomy, transverse sections of spinal cord at L5 level were prepared for morphometric cell count and TUNNEL assay. Results: The motor neuron loss in axotomized side compared to intact side was 30.48%, which illustrates the effectiveness of axotomy in inducing motoneuron cell death. The TUNNEL assay confirmed the apoptotic characteristics of cell death. Comparing the mean motoneurons loss in the axotomized side of the control and UA-treated neonates, revealed a significant difference between the two groups (p

References

  • 1.

    Graber MB, Moran LB. Mechanisms of cell death in neurodegenerative diseases: fashion, fiction and facts. Brain Pathol 2002; 12: 385-90.

  • 2.

    Honig LS, Rosenberg RN. Apoptosis and neurologic disease. Am J Med 2000; 108: 317-130.

  • 3.

    Yakoovlev AG, Faden AI. Mechanisms of cell death: implications for development of neuroprotective treatment strategies. Neuro Rx 2004; 1: 5-16.

  • 4.

    Israels LG, Israels ED. Apoptosis. Oncologist 1999; 4: 332-339.

  • 5.

    Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Scince 1995; 267: 1456-1462.

  • 6.

    Palace J. Neuroprotection and repair. J Neurol Sci 2008; 265: 21-25.

  • 7.

    Kinugasa T, Ozaki S, Hamanaka S, Kudo N. The effects of sciatic nerve axotomy on spinal motoneurons in neonatal Bax-deficient mice. Neurosc Res 2002; 44: 439-446.

  • 8.

    Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004; 291: 317-324.

  • 9.

    Squadrito GL, Cueto R, Splenser AE, Valavanidis A, Zhang H, Uppu RM, Pryor WA. Reaction of Uric Acid with Peroxynitrite and Implications for the Mechanism of Neuroprotection by Uric Acid. Arch Biochem Biophys 2000; 376: 333-337.

  • 10.

    Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyellitis and multiple sclerosis. Proc Natl Acad Sci USA 1998; 95: 675-680.

  • 11.

    Abraham A, Drory VE. Influence of serum uric acid levels on prognosis and survival in amyotrophic lateral sclerosis: a meta-analysis. Neurol 2014; 261: 1133-1138.

  • 12.

    Aoyama K, Matsumura N, Watabe M, Wang F, Kikuchi-utsumy K, Nakaki T. Caffeine and uric acid mediate glutathione neuroprotection. Neuroscience 2011; 181: 206-215.

  • 13.

    Phiffer CB, Terry LM. Use of hypothermia for general anesthesia in preweaning rodents. Physiol Behav 1986; 38: 887-890.

  • 14.

    Bahadori MH, Al-Tiraihi T, Valojerdi MR. Sciatic nerve transection in neonatal rats induces apoptotic neuronal death in L5 dorsal root ganglion. J Neurocytol 2001; 30: 125-130.

  • 15.

    Gage GJ, Kipke DR, Shain W. Whole animal perfusion fixation for rodents. J Vis Exp 2012; 65: 3564.

  • 16.

    Delshad A, Naseri M, Parvizi M, Fattah N, Sharayeli M. The Iranian traditional herbal medicine ostokhodus can prevent axotomy-induced apoptosis in spinal motoneurons in neonate rats. J Med Plant Res 2011; 5: 4446-4451.

  • 17.

    Deshad A, Parvizi M. The neuroprotective effect of Nepeta Mentoides on axotomized dorsal root ganglion sensory neuron in neonate rats. J Basic Clinical Pathophysiol 2014; 2: 13-20.

  • 18.

    Azizzadeh Delshad AR, Farzan AR. The prophylactic capacity of nepeta menthoides (ostokhodus) in prevention of spinal motoneuron injury. J Kerman Univ Med Sci 2013; 20: 20-30. (Persian).

  • 19.

    Groves MJ, Christopherson T, Giometto B, Scaravilli F. Axotomy-induced apoptosis in adult rat primary sensory neurons. Neurocytol 1997; 26: 615-624.

  • 20.

    Delshad A, Al-Tiraihi T. Ultrastructure of apoptotic oligodendrocytes in the spinal cord of adult rat with long-standing axotomized sciatc nerve. Folia Neuropathol 2001; 39: 125-128.

  • 21.

    Gao X, Chen H, Choi HK, Curhan G, Schwarzschild MA, Ascherio A. Diet, Urate and Parkinsons disease risk in men. Am J Epidemiol 2008; 167: 831-838.

  • 22.

    Zoccolella S, Tortorella C, Laffaldano P, Direnzo V, DOnghia M, Luciannatelli E, et al. Low serum Urate levels are associated to female gender in Multiple Sclerosis patients. Plos One 2012; 7: 221-226.

  • 23.

    Ashtari F, Bahar M, Aghaei M, Zahed A. Serum uric acid level in patients with relapsing-remitting multiple sclerosis. J Clin Neurosci 2013; 20: 676-678.

  • 24.

    Liu X, Liu M, Chen M, Ge QM, Pan SM. Serum uric acid is neuroprotective in Chinese patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator. J Stroke Cerebrovasc Dis 2015; 24: 1080-1086.

  • 25.

    Romanos E, Planas EM, Amaro S, Chamarro A. Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab 2007; 27: 14-20.

  • 26.

    Patel VP, Chu CT. Nuclear transport, oxidative stress, and neurodegeneration. Int J Clin Exp Pathol 2011; 4: 215-229.

  • 27.

    Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 1981; 78: 6858-6862.

  • 28.

    Du Y,Chen CP, Tseng CY, Eisenberg Y, Firestein BL. Astroglia mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity. Glia 2007; 55: 463-472.

  • 29.

    Drulovic J, Dujmovic I, Stojsavljev N, Mesaros S, Andjelkovic S. Uric acid levels in sera from patients with Multiple Sclerosis. Neurol 2001; 248: 121-126.