中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (3): 399-404.doi: 10.4103/1673-5374.245330

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

延迟轴突再密封促进脊髓损伤后的逆行神经元死亡

  

  • 出版日期:2019-03-15 发布日期:2019-03-15

Role of axon resealing in retrograde neuronal death and regeneration after spinal cord injury

William Rodemer 1 , Michael E. Selzer 1, 2   

  1. 1 Shriners Hospital Pediatric Research Center (Center for Neural Repair and Rehabilitation), Philadelphia, PA, USA
    2 Department of Neurology, the Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Michael E. Selzer, MD, PhD, michael.selzer@temple.edu.
  • Supported by:

    This work was supported by grants R01-NS092876 (NIH, to MES), SHC-85400 (Shriners Research Foundation, to MES), SHC-85220 (Shriners Research Foundation, to MES).

摘要:

orcid: 0000-0001-5091-4343(William Rodemer)
           0000-0002-1141-217X(Michael E. Selzer)

Abstract:

Spinal cord injury leads to persistent behavioral deficits because mammalian central nervous system axons fail to regenerate. A neuron’s response to axon injury results from a complex interplay of neuron-intrinsic and environmental factors. The contribution of axotomy to the death of neurons in spinal cord injury is controversial because very remote axotomy is unlikely to result in neuronal death, whereas death of neurons near an injury may reflect environmental factors such as ischemia and inflammation. In lampreys, axotomy due to spinal cord injury results in delayed apoptosis of spinal-projecting neurons in the brain, beyond the extent of these environmental factors. This retrograde apoptosis correlates with delayed resealing of the axon, and can be reversed by inducing rapid membrane resealing with polyethylene glycol. Studies in mammals also suggest that polyethylene glycol may be neuroprotective, although the mechanism(s) remain unclear. This review examines the early, mechanical, responses to axon injury in both mammals and lampreys, and the potential of polyethylene glycol to reduce injury-induced pathology. Identifying the mechanisms underlying a neuron’s response to axotomy will potentially reveal new therapeutic targets to enhance regeneration and functional recovery in humans with spinal cord injury.

Key words: axon resealing, regeneration, retrograde neuronal death, spinal cord injury, sea lamprey, PEG, mitochondrial dysfunction, calcium signaling