Inosine Accelerates the Regeneration and Anticipates the Functional Recovery after Sciatic Nerve Crush Injury in Mice

Neuroscience. 2019 Dec 15:423:206-215. doi: 10.1016/j.neuroscience.2019.09.023. Epub 2019 Nov 1.

Abstract

Trauma to the peripheral nervous system (PNS) results in loss of motor and sensory functions. After an injury, a complex series of events begins, allowing axonal regeneration and target reinnervation. However, this regenerative potential is limited by several factors such as age, distance from the lesion site to the target and severity of lesion. Many studies look for ways to overcome these limitations. Inosine, a purine nucleoside derived from adenosine, emerges as a potential treatment, due to its capacity to regulate axonal growth, neuroprotection and immunomodulation, contributing to motor recovery. However, no studies demonstrated their effects on PNS. C57/Black6 mice were submitted to sciatic nerve crush and received intraperitoneal injections of saline or inosine (70 mg/kg), one hour after injury and daily for one week. To evaluate axonal regeneration and functional recovery, electroneuromyography, Sciatic Function Index (SFI), rotarod and pinprick tests were performed. Our results showed that the inosine group presented a higher number of myelinated fibers and a large amount of fibers within the ideal G-ratio. In addition, the results of electroneuromyography showed greater amplitude of the compound muscle action potentials in the first and second weeks, suggesting anticipation of regeneration in the inosine group. We also observed in the inosine group, motor and sensory neurons survival, reduction in the number of macrophages and myelin ovoids in the sciatic nerves, and an early recovery of motor and sensory functions. Thus, we conclude that the use of inosine accelerates axonal regeneration promoting an early recovery of motor and sensory functions.

Keywords: SFI; crush injury; functional recovery; inosine; regeneration; sciatic nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electromyography
  • Injections, Intraperitoneal
  • Inosine / administration & dosage
  • Inosine / pharmacology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Nerve Crush*
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neuroprotective Agents / pharmacology
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / prevention & control*
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Rotarod Performance Test
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / injuries

Substances

  • Neuroprotective Agents
  • Inosine