Background: Spinal cord injury (SCI) is a major public health issue that leads to
neurological dysfunctions and morbidities in patients. Tetramethylpyrazine (TMP) plays a
neuroprotective role in SCI; however, the underlying mechanism has not been fully elucidated.
Objective: In the present study, we aimed to investigate the mechanisms and therapeutic effects of
TMP on SCI.
Methods: A contusion SCI model was established that used a modified Allen’s method. In the TMP
group, TMP (200 mg/kg) was injected daily for 5 days post-injury, while in the Negative Control
(NC) group, an equal volume of normal saline was injected. Hindlimb motor function was evaluated
using the Basso, Beattie, Bresnahan (BBB) scale. The effects of TMP on protein levels of the matrix
metalloproteinases 2 (MMP2) and 9 (MMP9), Bax and cleaved caspase-3 were determined by
western blotting. Apoptotic changes in vascular endothelial cells were evaluated using immunofluorescence
and TUNEL staining. Alterations in 3D vessel morphology after treatment with TMP
were assessed by synchrotron radiation micro-CT (SRμCT).
Results: TMP treatment significantly improved recovery in hindlimb motor function and attenuated
vascular endothelial cell apoptosis in rats with SCI. Additionally, TMP treatment markedly
decreased the protein levels of MMP2 and MMP9, pro-apoptotic bax and cleaved caspase-3 while
promoting angiogenesis, as evidenced by vessel visualization using SRμCT.
Conclusion: These results indicate that TMP attenuated SCI-induced neurological impairments by
the down-regulation of the expression of MMP2 and MMP9 proteins, the inhibition of vascular
endothelial cell apoptosis, and the promotion of angiogenesis.