ω-conotoxin MVIIA intralesional injection in spinal cord injury in rats

Oliveira, Karen Maciel de; Binda, Nancy Scardua; Lavor, Mário Sérgio Lima de; Silva, Carla Maria Osório; Rosado, Isabel Rodrigues; Taguchi, Tatiana Malagoli; Alves, Endrigo Gabellini Leonel; Melo, Marília Martins; Gomez, Marcus V.; Melo, Eliane Gonçalves de

doi:10.1590/0103-8478cr20141203

Cited by 2 publications

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References 21 publications

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“…In a previous study, our group tested intralesional MVIIA application 5 min after SCI, but results were not significant [ 36 ]. According to Valentino et al [ 31 ] and Verweij et al [ 30 ], MVIIA injection 15 min before [ 30 ] or even 1 h after [ 31 ] ischemic and traumatic brain injuries, respectively, does not preserve mitochondria as compared to MVIIA administration 4 h or 6 h after the trauma event [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…The compression lesion model used here is well established [ 36 , 38 – 40 ] and allowed us to reproduce moderate to severe injury efficiently. The model provides urinary retention and mimics conditions that often occur in humans [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

“…Then, the rat’s back was disinfected with antiseptic solution consisting of povidone-iodine, followed by alcohol 70%. The rats were positioned in a stereotaxic apparatus [ 36 , 38 – 41 ] and prepared for aseptic surgery. An incision was made in the dorsal midline skin and subcutaneous tissue extending from T8 to L1, and the muscle and tissue overlying the spinal column was blunt dissected away, to reveal the laminae.…”

Section: Methodsmentioning

confidence: 99%

“…By using the T13 spiny process as landmark, T12 laminectomy was performed with a pneumatic drill, and the lamina was carefully removed, to expose the spinal cord. Extradural moderate compression of the spinal cord at the T12 vertebral level was conducted for five minutes as described previously [ 36 , 38 , 39 ]; a 40.5 g.cm -1 weight was employed. Sham-operated rats (SHAM rats) did not receive the compression.…”

Section: Methodsmentioning

confidence: 99%

“…Given the peptidic nature of MVIIA, the cone snail toxins are not orally available and they must be delivered directly into the central nervous system (CNS) to avoid its degradation by proteolytic enzymes and the use of excessive MVIIA doses, which could lead to severe side effects. In a previous experiment [ 36 ], our group applied intralesional MVIIA directly on the target organ, which allowed targeted delivery of the optimal drug dose. However, MVIIA application five minutes after SCI did not promote neuroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

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Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord injury in rats

et al. 2018

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This study evaluates whether intrathecal MVIIA injection after spinal cord injury (SCI) elicits neuroprotective effects. The test rats were randomly distributed into six groups— sham, placebo, MVIIA 2.5 μM, MVIIA 5 μM, MVIIA 10 μM, and MVIIA 20 μM—and were administered the treatment four hours after SCI. After the optimal MVIIA dose (MVIIA 10 μM) was defined, the best time for application, one or four hours, was analyzed. Locomotor hind limb function and side effects were assessed. Forty-eight hours after the injury and immediately after euthanasia, spinal cord segments were removed from the test rats. Cell viability, reactive oxygen species, lipid peroxidation, and glutamate release were investigated. To examine the MVIIA mechanism of action, the gene expressions of pro-apoptotic (Bax, nNOS, and caspase-3, -8, -9, -12) and anti-apoptotic (Bcl-xl) factors in the spinal cord tissue samples were determined by real-time PCR, and the activities of antioxidant enzymes were also investigated. Application of intrathecal MVIIA 10 μM four hours after SCI prompted a neuroprotective effect: neuronal death decreased (22.46%), oxidative stress diminished, pro-apoptotic factors (Bax, nNOS, and caspase-3, -8) were expressed to a lesser extent, and mitochondrial viability as well as anti-apoptotic factor (Bcl-xl) expression increased. These results suggested that MVIIA provided neuroprotection through antioxidant effects. Indeed, superoxide dismutase (188.41%), and glutathione peroxidase (199.96%), reductase (193.86%), and transferase (175.93%) expressions increased. Therefore, intrathecal MVIIA (MVIIA 10 μM, 4 h) application has neuroprotective potential, and the possible mechanisms are related to antioxidant agent modulation and to intrinsic and extrinsic apoptotic pathways.

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