Elsevier

Experimental Neurology

Volume 159, Issue 1, September 1999, Pages 131-138
Experimental Neurology

Regular Article
Peripheral Nerve Graft and Neurotrophic Factors Enhance Neuronal Survival and Expression of Nitric Oxide Synthase in Clarke's Nucleus after Hemisection of the Spinal Cord in Adult Rat

https://doi.org/10.1006/exnr.1999.7134Get rights and content

Abstract

The present study examined the effects of peripheral nerve (PN) graft and neurotrophic factors on the expression of nitric oxide synthase (NOS) and the survival of Clarke's nucleus (CN) neurons at the first lumbar spinal segment (L1) 15 days after hemisection of the spinal cord at T11. Normal intact CN neurons did not express NOS. Forty-one percent of the ipsilateral CN neurons survived after hemisection at T11, and 48% of the surviving neurons expressed NOS. Transplantation of PN graft at the lesion site promoted the survival of CN neurons to 71% and increased the expression of NOS to 70%. Continuous infusion of brain-derived neurotrophic factor, ciliary neurotrophic factor, and neurotrophic-3, but not glial cell-derived neurotrophic factor, at the lesion site enhanced the survival of CN neurons to about 65%. Among the surviving neurons about 70% were NOS-positive. These results indicated that transplantation of autologous PN graft or continuous infusion of neurotrophic factors could enhance the survival of axotomized CN neurons. In addition, the survival-promoting function of the neurotrophic agents was coincided with the upregulation of the expression of NOS. However, whether the upregulation of NOS expression in injured CN neurons is related to the rescue function or is a side effect of the neurotrophic factors is not clear and needed further investigation.

References (46)

  • W. Wu

    Potential roles of gene expression change in adult rat spinal motoneurons following axonal injury: a comparison among c-jun, low-affinity nerve growth factor receptor (LNGFR), and nitric oxide synthase (NOS)

    Exp. Neurol.

    (1996)
  • W. Wu et al.

    Implantation of PNS graft inhibits the induction of neuronal nitric oxide synthase and enhances the survival of spinal motoneurons following root avulsion

    Exp. Neurol.

    (1994)
  • F.P. Zemlan et al.

    Ascending tracts of the lateral columns of the rat spinal cord: A study using the silver impregnation and horseradish peroxidase techniques

    Exp. Neurol.

    (1978)
  • M.F. Beal et al.

    Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid

    Nature

    (1986)
  • J.S. Beckman et al.

    Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide

    Proc. Natl. Acad. Sci. USA

    (1990)
  • J.P. Bolanos et al.

    Nitric oxide-mediated mitochondrial damage in the brain: Mechanisms and implications for neurodegenerative diseases

    J. Neurochem.

    (1997)
  • E. Bonfoco et al.

    Apoptosis and necrosis: Two distinct events induced, respectively, by mild and intense insults with N-methyl-d-aspartate or nitric oxide/superoxide in cortical cell cultures

    Proc. Natl. Acad. Sci. USA

    (1995)
  • V.L. Dawson et al.

    Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures

    Proc. Natl. Acad. Sci. USA

    (1993)
  • P.S. Diener et al.

    Neurotrophic factors prevent the death of CNS neurons after spinal cord lesions in newborn rats

    NeuroReport

    (1994)
  • A.G. Estevez et al.

    Nitric oxide-dependent production of cGMP supports the survival of rat embryonic motor neurons cultured with brain-derived neurotrophic factor

    J. Neurosci.

    (1998)
  • M. Gonzalez-Zulueta et al.

    Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediate neurotoxicity

    J. Neurosci.

    (1998)
  • R. Grill et al.

    Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury

    J. Neurosci.

    (1997)
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