Article
Application of Sonic Hedgehog in the acute phase after experimental spinal cord injury improves functional recovery and attenuates the inflammatory response
Die Applikation von Sonic Hedgehog in der akuten Phase nach experimenteller Rückenmarksverletzung verbessert die funktionelle Erholung und dämpft die Entzündungsreaktion
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Published: | May 25, 2022 |
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Objective: Although Sonic Hedgehog (Shh) has been extensively researched on its effects in early neurogenesis and brain development since its discovery in 1980, its recently described crucial neuroprotective effects implicate important underlying mechanisms on neuronal homeostasis and repair, especially after neuronal injury. We, therefore, studied the immediate effects of early applied Shh after acute spinal cord injury in rats.
Methods: In our experiment, we split 33 female Wistar rats into two survival groups: 72 hours and 168 hours. We performed a traumatic thoracic spinal cord injury (SCI) using the clip contusion/compression model at the T9 level or a sham surgery (laminectomy). Directly after the injury, animals were treated with topically applied Shh or a placebo (NaCl) via an intrathecal osmotic pump using a subdural catheter. Locomotor function was assessed daily using Gridwalk Test, Basso, Beattie and Bresnahan (BBB) score, and CatWalk gait analysis. Animals were sacrificed at the respective timepoints, and immunohistochemical analysis was performed to investigate inflammatory responses and migration of immune cells.
Results: Compared to animals in the placebo group, we found that Shh treated rats displayed a significantly improved functional recovery of hind leg movement and coordination, compared to untreated rats. Furthermore, then presence of immune cells around the lesion site was significantly reduced under Shh-treatment, indicating that Shh might affect cell migration. Shh-treated animals also showed a substantially higher tendency towards M2-differentiation of active macrophages. Interestingly, the Shh-treatment also led to less blood plasma products in and around the lesion, suggesting that Shh has relevant effects on the permeability of the blood-spinal cord-barrier (BSCB).
Conclusion: Topically applied Shh displayed various immediate immunomodulatory effects by supposed BSCB tightening, reduced immune cell migration and anti-inflammatory immune cell differentiation, thus resulting in improved locomotor recovery.