title: 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.
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Oliveira
authors.affiliation: Departamento de Ciências Agrárias e Ambientais, Universidade Estadual de Santa Cruz Ilhéus-Bahia, Brazil.
authors.forename: Mário Sérgio L
authors.initials: MS
authors.lastname: Lavor
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Carla Maria O
authors.initials: CM
authors.lastname: Silva
authors.affiliation: Universidade Federal do Paraná, Campus de Palotina Palotina-Paraná, Brazil.
authors.forename: Fabíola B
authors.initials: FB
authors.lastname: Fukushima
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Rosado
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Juneo F
authors.initials: JF
authors.lastname: Silva
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Bernardo C
authors.initials: BC
authors.lastname: Martins
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Laís B
authors.initials: LB
authors.lastname: Guimarães
authors.affiliation: Laboratório Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Marcus Vinícius
authors.initials: MV
authors.lastname: Gomez
authors.affiliation: Universidade Federal do Paraná, Campus de Palotina Palotina-Paraná, Brazil.
authors.forename: Marília M
authors.initials: MM
authors.lastname: Melo
authors.affiliation: Departamento de Medicina e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais Belo Horizonte-Minas Gerais, Brazil.
authors.forename: Eliane G
authors.initials: EG
authors.lastname: Melo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000473:pathology*; D020960:omega-Conotoxins / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC
keywords: In vitro; bladder; cell death; clinical recovery; conotoxin; neuron preservation