Article
Substance P is associated with early secondary injury processes after traumatic spinal cord injury
Substanz P ist mit frühen sekundären Verletzungsprozessen nach traumatischer Rückenmarksverletzung assoziiert
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Authors
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Carola Wieckhusen
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Stefan Heene
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Guoli Zheng
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Hao Wang
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Obada T. Alhalabi
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Thomas Skutella
- Universitätsklinikum Heidelberg, Neuroanatomy, Heidelberg, Deutschland
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Andreas W. Unterberg
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Klaus Zweckberger
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Alexander Younsi
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Traumatic spinal cord injury (tSCI) is a devastating event, often associated with lifelong disability. Secondary to the primary injury, a cascade of secondary injury processes including blood-spinal cord barrier (BSCB) disintegration and neuroinflammation is initiated, leading to aggravation of symptoms and impaired regeneration. The Substance P (SP) mediated pathway has been associated with mediating such sequelae. Therefore, our current experiment aimed to determine the effects of a SP-treatment in the acute phase after tSCI.
Methods: A total of 78 female Wistar rats were randomized and received a T9-compression/contusion-SCI (SP, Placebo; n=30 each) or a laminectomy only (Sham; n=18). During the same surgery, a micropump for continuous i.t. delivery of SP or Placebo for 7 days was implanted. Neurological function was assessed 1, 3 and 7 days after SCI as well as weekly thereafter (CatWalk gait analysis, BBB score and Gridwalk test). The experiment was terminated by perfusion of the animals at different timepoints (3, 7 and 28 days after SCI). After tissue preparation, immunfluoerscence analysis was performed and the influence of SP on neuroinflammation, and BSCB integrity was assessed. Spinal cord edema was additionally measured with the wet/dry weight method 3 days after SCI. Results between groups were statistically compared (p < 0,05 was considered significant).
Results: Though mostly not significant, immunofluorescence stainings with different markers indicated that the i.t. administration of SP directly after the thoracic compression/contusion-SCI might have positive effects on neuroinflammation and BSCB-integrity on a histological level. Similarly, spinal cord edema in the wet/dry spinal cord weight assay was slightly reduced in the SP group early after SCI, though not significantly. More importantly, long-term functional recovery seemed to be improved in SP-treated animals: After 28 days the BBB score was 3.0 points higher compared to placebo animals (significant, p<0.001) and a trend towards better outcomes with the SP-treatment was seen in the Gridwalk test and and CatWalk gait analysis as well.
Conclusion: Our current study presents findings on the association of intrathecally administered SP with neuroinflammation, BSCB integrity, spinal cord edema and functional recovery after SCI. Targeting the SP pathway might become a valuable treatment option for SCI and should further investigated.
