Valproic acid preserves motoneurons following contusion in organotypic spinal cord slice culture

Abstract

Objective: Spinal cord injury (SCI) is a devastating condition causing neuronal loss. A key challenge in treatment of SCI is how to retain neurons after injury. Valproic acid (VPA) is a drug recently has been appreciated for its neuroprotective and neurotrophic properties in various SCI models. In this study the role of VPA was assessed in organotypic spinal cord slice culture following the contusion.

Design: The lumbar enlargement of adult rat was cut transversely and slices were cultured. Seven days after culturing, injury was induced by dropping a 0.5 gram weight from 3 cm height on the slice surface. One hour after injury, the VPA was administered at 1, 5 and 10 µM concentrations. Afterward, at day 1 and 3 post injury (DPI: 1 and 3) propidium iodide (PI) and immunohistochemistry staining were performed to evaluate the cell death, NeuN and β-Tubulin expression, respectively.

Results: The PI staining of slices at DPI: 1 and 3 following treatment with VPA revealed significant decreases in the cell death in all three concentrations comparing to the non-treated group. Also immunostaining showed VPA only at 5 µM concentration considerably rescued ventral horn’ MNs from death and protected the neuronal integrity.

Conclusion: The results of this study indicate applying VPA one hour after injury can prevent the death of a majority of cells, importantly MNs and preserve the neuronal integrity. Since the first 24 hours after SCI is a critical period for employing any treatment, VPA can be considered as an option for further evaluation.

Keywords:

• Contusion
• Spinal cord
• Traumatic injury
• Valproic acid

Acknowledgment

The authors are thankful to the Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, for the financial support of this work. Also they would like to thank Ms Soudabeh Ghasemi for her technical assistance.

Disclaimer Statements

Funding None.

Conflicts of interest The authors declare that they have no conflict of interests.

Ethics approval None.