Intranasal delivery of tetramethylpyrazine alleviates kainic acid-induced hippocampal neuronal death

Objective: This study aims to investigate the therapeutic activity and mechanism of tetramethylpyrazine (TMP) in kainic acid (KA)-induced neuronal death. Methods: : The epileptic mouse model was induced by kainic acid. Male BALB/c mice were randomized into three groups: control , KA and KA + TMP , 10 mice in each group. In the KA and KA + TMP groups, PBS or TMP was administered through the nasal cavity 15 minutes before KA injection. The time of seizure in each group was recorded and the survival of neurons in mouse hippocampus was observed by immunohistochemistry. The expression of proinflammatory markers (COX-2, TNF-α and IL-1β) in the hippocampus was detected by Real time-PCR. Finally, the induction of p65 NF-κB in CA1 and CA3 regions was analyzed by Western blot. Results: : It was found that administration of 2.5 mg/kg TMP could reduce KA-induced neuronal death. TMP suppressed KA-induced gliosis and expression of proinflammatory markers. Meanwhile, the induction of p65 NF-κB was decreased by TMP in KA-treated mouse hippocampus. Conclusion: TMP promotes the survival of neurons in KA-treated mouse hippocampus by inhibiting inflammatory process.