Paclitaxel Inhibits Expression of Neuronal Nitric Oxide Synthase and Prevents Mitochondrial Dysfunction in Spinal Ventral Horn in Rats After C7 Spinal Root Avulsion

Turk Neurosurg. 2015;25(4):617-24. doi: 10.5137/1019-5149.JTN.14035-15.1.

Abstract

Aim: This study evaluated the neuroprotective effect of intrathecally infused paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury.

Material and methods: Brachial root avulsion injury was induced in Sprague-Dawley rats. The Paclitaxel treatment group (n = 32) received a 5-d intrathecal infusion of paclitaxel (256 ng/d) via a micro infusion pump, whereas the Control group (n = 32) received normal saline. The cervical cord was harvested at survival times of 1, 2, 4, and 6 wk (n = 8 each). The number of surviving and nNOS-positive motoneurons at the injury level in the ventral horn was determined with NADPH-d histochemistry. Mitochondrial function at this location was measured with CcO histochemistry and densitometry. An independent t-test was applied to detect differences between the study groups at specific survival times.

Results: The Paclitaxel treatment group showed a significant relative reduction in nNOS expression at 2, 4, and 6 wk, and significantly improved mitochondrial function at 4 and 6 wk. Motoneuron survival was significantly increased at 2, 4, and 6 wk.

Conclusion: Paclitaxel has a significant neuroprotective effect against spinal motoneuron degeneration following brachial plexus avulsion injury, which involves inhibition of nNOS expression and prevention of mitochondrial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Horn Cells / drug effects*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Brachial Plexus / injuries
  • Cell Death / drug effects
  • Electron Transport Complex IV / metabolism
  • Female
  • Injections, Spinal
  • Mitochondrial Diseases / prevention & control*
  • Motor Neurons / drug effects
  • NADPH Dehydrogenase / metabolism
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide Synthase Type I / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I / biosynthesis*
  • Paclitaxel / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / pathology
  • Spinal Nerve Roots / drug effects*

Substances

  • Antineoplastic Agents, Phytogenic
  • Neuroprotective Agents
  • Nitric Oxide Synthase Type I
  • NADPH Dehydrogenase
  • Electron Transport Complex IV
  • Paclitaxel