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Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats.

Abstract
Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements.
AuthorsKaren M Oliveira, Mário Sérgio L Lavor, Carla Maria O Silva, Fabíola B Fukushima, Isabel R Rosado, Juneo F Silva, Bernardo C Martins, Laís B Guimarães, Marcus Vinícius Gomez, Marília M Melo, Eliane G Melo
JournalInternational journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 7 Issue 7 Pg. 3524-36 ( 2014) ISSN: 1936-2625 [Electronic] United States
PMID25120731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Neuroprotective Agents
  • omega-Conotoxins
  • omega-conotoxin-MVIIC
Topics
  • Animals
  • Apoptosis (drug effects)
  • Disease Models, Animal
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Male
  • Neurons (drug effects)
  • Neuroprotective Agents (pharmacology)
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Recovery of Function (drug effects)
  • Spinal Cord Injuries (pathology)
  • omega-Conotoxins (pharmacology)

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