Neuroprotective efficiency of tetanus toxin C fragment in model of global cerebral ischemia in Mongolian gerbils

Brain Res Bull. 2014 Feb;101:37-44. doi: 10.1016/j.brainresbull.2013.11.006. Epub 2013 Dec 21.

Abstract

The tetanus toxin C (TTC) fragment capacity of being transported in a retrograde way through motoneurons and its nontoxic nature opens the door to a new promising therapeutic strategy for neurodegenerative diseases. In this study, the TTC effect was tested for the first time in animal model of global cerebral ischemia induced by 10-min occlusion of both common carotid arteries. The aim was to evaluate the effect of TTC gene therapy treatment on the development and expression of global cerebral ischemia/reperfusion-induced oxidative stress and motor hyperactivity in Mongolian gerbils. Several oxidative stress and motor behavioral parameters were investigated between 2 h and 14 days after reperfusion. Neuroprotective efficiency of TTC was observed in the forebrain cortex, striatum, hippocampus, and cerebellum at the level of each examined oxidative stress parameter (nitric oxide level, superoxide production, superoxide dismutase activity, and index of lipid peroxidation). Additionally, TTC significantly decreased ischemia-induced motor hyperactivity based on tested parameters (locomotion, stereotypy, and rotations). As judged by biochemical as well as behavioral data, treatment with TTC for the first time showed neuroprotective efficiency by reduction of ischemia-induced oxidative stress and motor hyperactivity and can be a promising strategy for ischemia-induced neuronal damage treatment.

Keywords: Global ischemia; Motor behavior; Neuroprotection; Oxidative stress; TTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiopathology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Carotid Artery, Common
  • DNA, Recombinant
  • Genetic Therapy*
  • Gerbillinae
  • Hyperkinesis / physiopathology
  • Hyperkinesis / therapy
  • Male
  • Motor Activity / physiology
  • Neuroprotective Agents*
  • Oxidative Stress / physiology
  • Peptide Fragments / genetics*
  • Plasmids*
  • Random Allocation
  • Tetanus Toxin / genetics*
  • Time Factors
  • Treatment Outcome

Substances

  • DNA, Recombinant
  • Neuroprotective Agents
  • Peptide Fragments
  • Tetanus Toxin
  • tetanus toxin fragment C