title: Paclitaxel Inhibits Expression of Neuronal Nitric Oxide Synthase and Prevents Mitochondrial Dysfunction in Spinal Ventral Horn in Rats After C7 Spinal Root Avulsion.
abstract: OBJECTIVE
  This study evaluated the neuroprotective effect of intrathecally infused paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Universiti Malaysia Sarawak, Faculty of Medicine and Health Sciences, Department of Surgery, Kota Samarahan, Sarawak, Malaysia.
authors.forename: Sze Kiat
authors.initials: SK
authors.lastname: Sim
authors.forename: Yew Chin
authors.initials: YC
authors.lastname: Tan
authors.forename: Jong Huat
authors.initials: JH
authors.lastname: Tee
authors.forename: Abdul Aziz
authors.initials: AA
authors.lastname: Yusoff
authors.forename: Jafri Malin
authors.initials: JM
authors.lastname: Abdullah
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001917:Brachial Plexus / Q000293:injuries; D016923:Cell Death / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D007278:Injections, Spinal; D028361:Mitochondrial Diseases / Q000517:prevention & control*; D009046:Motor Neurons / Q000187:drug effects; D009252:NADPH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013126:Spinal Nerve Roots / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018696:Neuroprotective Agents; D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase; D003576:Electron Transport Complex IV; D017239:Paclitaxel