Abstract: BACKGROUND: Animal experiments have found that epothilone B can remodel blood microcirculation and reduce tissue scar formation after spinal cord injury, but the specific mechanism remains unclear.  
OBJECTIVE: To clarify the mechanism by which epothilone B improves spinal cord microcirculation after spinal cord injury.  
METHODS: Fifty Sprague-Dawley rats were randomly divided into a sham-operated group (n=10), a spinal cord injury group (n=20), and an epothilone B group (n=20). The sham-operated group underwent only laminectomy at T10, while the other two groups were subjected to laminectomy at T10 followed by spinal cord contusion. Immediately after modeling, the epothilone B group received intraperitoneal injections of Epothilone B solution, while the other two groups received corresponding solvents. At corresponding time points post-modeling, Basso-Beattie-Bresnahan scores, inclined plane tests, and open field tests were used to assess motor function. Laser speckle contrast imaging was employed to measure blood flow recovery in the posterior median spinal vessels. Hematoxylin-eosin staining was used to evaluate overall spinal tissue conditions. Western blot was performed to detect Toll-like receptor 4 and nuclear factor κB protein expression. Immunofluorescence staining was used to assess vascular endothelial growth factor receptor 2 and Toll-like receptor 4 expression in spinal cord injury tissues.  
RESULTS AND CONCLUSION: At 14 and 28 days post-modeling, the Basso-Beattie-Bresnahan scores in the Epothilone B group were higher than those in the spinal cord injury group (P < 0.05). At 28 days post-modeling, the inclined plane test angle was greater in the epothilone B group than the spinal cord injury group (P < 0.05). At 14 and 28 days post-modeling, the movement distance in the open field test was greater in the epothilone B group than in the spinal cord injury group (P < 0.05), indicating that epothilone B improved motor function in rats with spinal cord injury. Laser speckle contrast imaging at 28 days post-modeling showed that epothilone B enhanced blood flow recovery in rats with spinal cord injury. Hematoxylin-eosin staining at 28 days post-modeling revealed that the spinal cavity area was smaller in the epothilone B group than in the spinal cord injury group (P < 0.05). Western blot analysis at 5 days post-modeling showed that Toll-like receptor 4 and nuclear factor κB protein expression was higher in the spinal cord injury group than in the sham-operated and epothilone B groups (P < 0.05). Immunofluorescence staining at 5 days post-modeling demonstrated that vascular endothelial growth factor receptor 2 expression was lower in the spinal cord injury group than in the sham-operated and Epothilone B groups (P < 0.05), while Toll-like receptor 4 expression was higher in the spinal cord injury group than in the sham-operated and epothilone B groups (P < 0.05). These findings suggest that Epothilone B may alleviate local inflammation after spinal cord injury by regulating the Toll-like receptor 4 and nuclear factor κB pathways, thereby ensuring vascular endothelial cell regeneration within the spinal tissue and promoting the reconstruction of blood microcirculation.

Key words: spinal cord injury, epothilone B, microcirculation, vascular endothelial growth factor, mechanism, nuclear factor κB, Toll-like receptor 4