Effect of vasodilators and myelotomy on recovery after acute spinal cord injury in rats

Rivlin, Alex S.; Tator, Charles H.

doi:10.3171/jns.1979.50.3.0349

Cited by 32 publications

(17 citation statements)

References 7 publications

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“…The rat was placed on an inclined plane covered by a rubber mat (with 0.6 mm deep grooves) constructed as reported [56,57]. The plane can be adjusted to different slopes to measure the animal's ability to maintain its body position for 5 sec without falling.…”

Section: Methodsmentioning

confidence: 99%

Mn (III) tetrakis (4-benzoic acid) porphyrin scavenges reactive species, reduces oxidative stress, and improves functional recovery after experimental spinal cord injury in rats: comparison with methylprednisolone

et al. 2013

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BackgroundSubstantial experimental evidence supports that reactive species mediate secondary damage after traumatic spinal cord injury (SCI) by inducing oxidative stress. Removal of reactive species may reduce secondary damage following SCI. This study explored the effectiveness of a catalytic antioxidant - Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) - in removing reactive oxygen species (ROS), reducing oxidative stress, and improving functional recovery in vivo in a rat impact SCI model. The efficiency of MnTBAP was also compared with that of methylprednisolone – the only drug used clinically in treating acute SCI.ResultsIn vivo measurements of time courses of ROS production by microdialysis and microcannula sampling in MnTBAP, methylprednisolone, and saline (as vehicle control)-treated SCI rats showed that both agents significantly reduced the production of hydrogen peroxide, but only MnTBAP significantly reduced superoxide elevation after SCI. In vitro experiments further demonstrated that MnTBAP scavenged both of the preceding ROS, whereas methylprednisolone had no effect on either. By counting the immuno-positive neurons in the spinal cord sections immunohistochemically stained with anti-nitrotyrosine and anti-4-hydroxy-nonenal antibodies as the markers of protein nitration and membrane lipid peroxidation, we demonstrated that MnTBAP significantly reduced the numbers of 4-hydroxy-nonenal-positive and nitrotyrosine-positive neurons in the sections at 1.55 to 2.55 mm and 1.1 to 3.1 mm, respectively, rostral to the injury epicenter compared to the vehicle-treated animals. By behavioral tests (open field and inclined plane tests), we demonstrated that at 4 hours post-SCI treatment with MnTBAP and the standard methylprednisolone regimen both significantly increased test scores compared to those produced by vehicle treatment. However, the outcomes for MnTBAP-treated rats were significantly better than those for methylprednisolone-treated animals.ConclusionsThis study demonstrated for the first time in vivo and in vitro that MnTBAP significantly reduced the levels of SCI-elevated ROS and that MnTBAP is superior to methylprednisolone in removing ROS. Removal of ROS by MnTBAP significantly reduced protein nitration and membrane lipid peroxidation in neurons. MnTBAP more effectively reduced neurological deficits than did methylprednisolone after SCI - the first most important criterion for assessing SCI treatments. These results support the therapeutic potential of MnTBAP in treating SCI.

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Section: Methodsmentioning

confidence: 99%

Mn (III) tetrakis (4-benzoic acid) porphyrin scavenges reactive species, reduces oxidative stress, and improves functional recovery after experimental spinal cord injury in rats: comparison with methylprednisolone

et al. 2013

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“…Each rat was placed on an inclined plane covered by a rubber mat (with 0.6 mm deep grooves) constructed as reported [58,59]. The plane can be adjusted to different slopes to measure the animal’s ability to maintain its body position for 5 sec without falling.…”

Section: Methodsmentioning

confidence: 99%

The temporal and spatial profiles of cell loss following experimental spinal cord injury: effect of antioxidant therapy on cell death and functional recovery

et al. 2013

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BackgroundTraumatic spinal cord injury (SCI)-induced overproduction of endogenous deleterious substances triggers secondary cell death to spread damage beyond the initial injury site. Substantial experimental evidence supports reactive species (RS) as important mediators of secondary cell death after SCI. This study established quantitative temporal and spatial profiles of cell loss, characterized apoptosis, and evaluated the effectiveness of a broad spectrum RS scavenger - Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) and a combination of MnTBAP plus nitro-L-arginine to prevent cell loss and neurological dysfunction following contusion SCI to the rat spinal cord.ResultsBy counting the number of surviving cells in spinal cord sections removed at 1, 6, 12, 24, 48, 72 h and 1 week post-SCI and at 0 – 4 mm from the epicenter, the temporal and spatial profiles of motoneuron and glia loss were established. Motoneurons continued to disappear over a week and the losses decreased with increasing distance from the epicenter. Significant glia loss peaked at 24 to 48 h post-SCI, but only at sections 0–1.5 mm from the epicenter. Apoptosis of neurons, motoneurons and astrocytes was characterized morphologically by double immuno-staining with cell-specific markers and apoptosis indicators and confirmed by transmission electron microscopy. DNA laddering, ELISA quantitation and caspase-3 activation in the spinal cord tissue indicated more intense DNA fragments and greater caspase-3 activation in the epicenter than at 1 and 2 cm away from the epicenter or the sham-operated sections. Intraperitoneal treatment with MnTBAP + nitro-L-arginine significantly reduced motoneuron and cell loss and apoptosis in the gray and white matter compared with the vehicle-treated group. MnTBAP alone significantly reduced the number of apoptotic cells and improved functional recovery as evaluated by three behavioral tests.ConclusionsOur temporal and spatial profiles of cell loss provide data bases for determining the time and location for pharmacological intervention. Our demonstration that apoptosis follows SCI and that MnTBAP alone or MnTBAP + nitro-L-arginine significantly reduces apoptosis correlates SCI-induced apoptosis with RS overproduction. MnTBAP significantly improved functional recovery, which strongly supports the important role of antioxidant therapy in treating SCI and the candidacy of MnTBAP for such treatment.

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“…5,6,8,10,11 Previous studies have shown that myelotomy significantly improves functional recovery when compared with opening of the meninges after SCI. 7,12 However, questions are raised regarding application of myelotomy for SCI, such as suitable operation timing. From the perspective of the reduction of intramedullary pressure, myelotomy should be performed as soon as possible after SCI; from the perspective of the debridement of aseptic necrosis, myelotomy should be performed with a fully liquefied lesion and a clear anatomical delimitation in order to get an adequate drainage, and to minimize the risk of potential surgical damage.…”

Section: Introductionmentioning

confidence: 99%

Optimal time window of myelotomy in rats with acute traumatic spinal cord injury: a preliminary study

et al. 2013

Spinal Cord

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Objectives: Pathophysiological mechanisms underlying spinal cord injury (SCI) partially involve edema and formation of a hematoma. Myelotomy seems to be a promising intervention. However, the appropriate timing of myelotomy is still unknown in SCI. Here we aimed to determine the timing of microsurgical myelotomy in an animal model of SCI. Methods: The SCI model was contusion-induced with a new york university impactor. Sixty-five adult female rats were randomly divided into the following groups: laminectomy alone (the 'sham group', SG), laminectomy plus contusion (the 'contusion group', CG) or laminectomy plus contusion followed by myelotomy at 8, 24 or 48 h (8 h-MTG [myelotomy-treated group], 24 h-MTG or 48 h-MTG). Functional recovery was evaluated via the open field test and the inclined plane test every week after SCI. The percentage of spared white matter area (SWMA) and ultrastructure characteristics of the injured dorsolateral spinal cord were determined on the 42nd day after SCI. Results: Compared with the CG, myelotomy at 8 h-MTG or 24 h-MTG greatly improved the BASSO-BEATTIE-BRESNAHAN scores (Po0.008), whereas the 48 h-MTG showed less efficacy (P ¼ 0.023). All myelotomy groups showed higher mean angle values in an inclined plane test (Po0.005) and had greater percentages of SWMA than the CG. Rats in the 24 h-MTG showed a higher intraaxonal fraction and myelin fraction than those in 48 h-MTG (Po0.005). Conclusion: Myelotomy up to 48 h after SCI improves recovery in rats. The potential time window of myelotomy may be between 8 and 24 h after SCI.

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Effect of vasodilators and myelotomy on recovery after acute spinal cord injury in rats

Cited by 32 publications

References 7 publications

Mn (III) tetrakis (4-benzoic acid) porphyrin scavenges reactive species, reduces oxidative stress, and improves functional recovery after experimental spinal cord injury in rats: comparison with methylprednisolone

Mn (III) tetrakis (4-benzoic acid) porphyrin scavenges reactive species, reduces oxidative stress, and improves functional recovery after experimental spinal cord injury in rats: comparison with methylprednisolone

The temporal and spatial profiles of cell loss following experimental spinal cord injury: effect of antioxidant therapy on cell death and functional recovery

Optimal time window of myelotomy in rats with acute traumatic spinal cord injury: a preliminary study

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