Article
Effects of a new treatment approach with sonic hedgehog on neuroregeneration after thoracic spinal cord injury in rats
Einfluss eines neuen Behandlungsansatzes mit Sonic Hedgehog auf die Neuroregeneration nach thorakaler Rückenmarksverletzung in der Ratte
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Published: | May 8, 2019 |
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Objective: Traumatic spinal cord injury (SCI) remains a devastating neurosurgical disease with limited functional recovery due secondary changes like neuroinflammation, scarring and astrogliosis. Up to now, no therapeutic approach for the improvement of neuroregeneration is available for affected patients. The Sonic Hedgehog (SHH) pathway which participates in e.g. vascular proliferation, differentiation, and tissue repair has recently been associated with a protective role after CNS injury by promoting barrier formation and by acting as an endogenous anti-inflammatory system. We therefore examined the effects of intrathecal SHH application as a new treatment approach after thoracic SCI in rats.
Methods: 71 Wistar rats were subjected to thoracic clip-contusion/compression injury at Th10. Animals were randomized into three treatment groups (SHH, Vehicle, Sham) and SHH was intrathecally infused with an osmotic pump for 1, 3 and 7 days. To assess functional recovery, the Basso, Beattie and Bresnahan (BBB) score as well as the CatWalk XT gait analysis were performed. After sacrifice, frozen tissue sections were obtained and immunohistological analyseswere conducted. Results were compared between groups statistically analyzed (p<0.05 was considered significant).
Results: Animals in the SHH treatment group showed less weight loss compared to vehicle animals over the course of the experiment. Accordingly, the BBB score had significantly improved in these animals 7 days after SCI. In addition, the CatWalk gait analysis showed a strong trend towards better improvement in the regularity index as well as in the stride length and paw intensity of the SHH treated animals. In immunhistological analysis, expression of inflammation markers was significantly reduced in SHH treated animals when compared to vehicle animals. In addition, assessment of blood spinal cord barrier (BSCB) integrity revealed less fibrinogen extravasation and more tight junctions in animals that received the SHH treatment.
Conclusion: In our study, the intrathecal administration of SHH lead to improved functional recovery 7 days after thoracic SCI. Changes in the BSCB integrity and modulation of neuroinflammation in the injured tissue might mediate these positive effects on neuroregeneration.