Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury

ObjectiveInflammation, which is known to be detrimental to the neurologic outcome during the acute phase after an ischemic stroke, provides a potential target for preventive or therapeutic approach for spinal cord ischemia-reperfusion injury. Tetramethylpyrazine (TMP), a pure compound derived from Ligusticum chuanxiong, is widely used in the treatment of ischemic stroke. The present study aimed to gain a deeper insight into the mechanism underlying the anti-inflammatory effects of TMP on spinal cord ischemia-reperfusion injury.MethodsSpinal cord ischemia was induced in male Sprague-Dawley rats by balloon occlusion of the thoracic aorta. The experimental groups (n = 30 per group) included sham operation, control (receiving only normal saline), and TMP (30 mg/kg, 30 minutes before occlusion). Neurologic function was assessed by the Basso, Beattie, and Bresnahan (BBB) score at 1, 6, 12, 24, and 48 hours after reperfusion. Histologic changes were studied using Nissl staining. Infarct volume was analyzed using 2,3,5-triphenyltetrazolium chloride staining. Myeloperoxidase (MPO) activity was determined by using a rat MPO assay kit. Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-10 and nuclear factor (NF)-κB were examined with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blotting.ResultsCompared with the control group, the TMP group showed significantly improved neurologic outcome (P < .05), decreased infarct volume (42.3% vs 17.4%), and alleviated neutrophil infiltration (0.35 vs 0.18 U/g). TMP treatment reduced the expressions of proinflammatory cytokines TNF-α (28.62 vs 15.23 pg/mg protein) and IL-1β (13.62 vs 8.24 pg/mg protein), upregulated the expression of anti-inflammatory cytokine IL-10 (18.35 vs 31.26 pg/mg protein), and inhibited the activation of NF-κB (2.78 vs 1.22) in ischemic spinal cord.ConclusionsTreatment with TMP exerted a neuroprotective effect against spinal cord ischemia-reperfusion injury. The anti-inflammatory effect was believed to be one of the contributing mechanisms.

Clinical RelevanceSpinal cord injury after surgical repair of thoracic or thoracoabdominal aorta is a disastrous complication. However, the exact mechanism of this delayed vulnerability is not fully understood. Inflammatory reaction after ischemic insult can be thought of as one of the mechanisms responsible for delayed infarct expansion leading to subacute or delayed paraplegia. Tetramethylpyrazine (TMP), a purified and chemically identified component of the Chinese herbal medicine Chuanxiong has known anti-inflammatory properties and was therefore expected to suppress such postischemic inflammatory reaction. In this study, TMP exhibited significant neuroprotective effects against spinal cord ischemia-reperfusion injury by reduction of behavioral disturbance and neuronal loss. TMP markedly downregulated the proinflammatory cytokines of tumor necrosis factor-α, interleukin (IL)-1β, and upregulated the anti-inflammatory cytokine of IL-10. Moreover, spinal cord I/R-induced inflammatory cell infiltration and nuclear factor-κB activation were inhibited by TMP treatment. These results suggest that TMP might provide neuroprotection against spinal cord ischemia-reperfusion injury through reducing inflammatory response. After clarification of the more comprehensive protective mechanism, optimal dose, and timing, TMP may be used in humans as an adjunct to eliminate this catastrophic complication.