Treatment with valproic acid for spinal cord injury in mice

• Main Authors: Ying-ShuangChang, 張瀛双
• Other Authors: Jung-Yu Hsu
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/03897068170410285826

碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 100 === Damaged axons cannot regenerate after spinal cord injury. One major reason for this regenerative failure is the formation of a glial scar. The glial scar, consisting mainly of reactive astrocytes, not only forms a barrier that blocks regenerative axons but also expresses inhibitory molecules chondroitin sulfate proteoglycans (CSPGs) that arrest axon regrowth. Reducing the formation of the glial scar, therefore, is essential for axonal regeneration after spinal cord injury. Valproic acid (VPA) is one candidate that shows such therapeutic potential. As an anti-epileptic drug already in clinical use to treat psychiatric bipolar disorders, VPA can reduce intermediate filaments that affect astrocyte mobility. It also exhibits neuroprotective and neurotrophic properties and has been used to treat several neurodegenerative diseases. To evaluate its therapeutic effect, therefore, I administered VPA subcutaneously to mice after a moderate spinal cord contusion injury at the mid-thoracic level. Immunohistochemistry demonstrated that VPA-treated mice showed a trend toward less GFAP and CGRP immunoreactivity with significant more residual white matter stained by luxol fast blue than the control mice 21 and 42 days after injury. However, the numbers of serotonergic and calcitonin gene-related protein-positive axons were comparable between VPA-treated and control mice. Likewise, both VAP-treated and control mice showed similar extent of functional recovery in a battery of motor and sensory behavior tests at all time points examined. Collectively, my study demonstrates that the effect of VPA treatment appears to be marginal after spinal cord injury. More studies on VPA dosage and treatment time are needed to further evaluate its therapeutic potential to treat spinal cord injury.