The Neuroprotective Effect of Tetramethylpyrazine Against Contusive Spinal Cord Injury by Activating PGC-1 alpha in Rats

摘要

Tetramethylpyrazine (TMP) has been suggested to have neuroprotective effects against spinal cord injury (SCI); however, few studies have examined these effects and the corresponding mechanism. Therefore, the present study aimed to investigate the neuroprotective effect and underlying mechanism of TMP against contusive SCI. Adult male Sprague-Dawley rats were randomly divided into Sham, normal saline (NS) and TMP groups. Each group was divided into subgroups according to the time of sacrifice: 1, 3, 7, 14, 21 and 28 days post-injury. Laminectomy was performed in all groups, followed by contusive SCI establishment in the TMP and NS groups. TMP (80 mg/kg) was injected thereafter daily from 3 to 7 days post-injury in the TMP group, which was replaced by equal volume of normal saline in the NS group. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale was measured at different time points post-injury to appraise locomotor functional recovery. Quantitative real-time PCR and immunofluorescence were used to assess the spatio-temporal expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), while western blot was adopted to detect the effect of TMP on PGC-1 alpha. Neural apoptotic changes and neuronal survival were evaluated using the TUNEL method and Nissl staining, respectively. TMP treatment markedly increased PGC-1 alpha expression, neuronal survival and BBB locomotor scores, while also reducing neural apoptosis. These results demonstrate that TMP is neuroprotective against contusive SCI, with the inhibition of neural apoptosis and increase of neuronal survival. The sustained expression of PGC-1 alpha may partially contribute to the TMP-mediated neuroprotective effect.