Abstract

BACKGROUND: To explore the theoretical basis for protecting the brain from ischemic stroke with tetramethylpyrazine, we studied whether and how tetramethylpyrazine could protect neurons against the oxygen-glucose deprivation (OGD)-induced death and whether transient receptor potential cation channel, subfamily C, member 6 (TRPC6) was involved.

MATERIAL AND METHODS: Primary rat cortical neurons were cultured and an OGD model was established in the presence or absence of tetramethylpyrazine. Neuronal death was assessed by measuring the uptake of membrane-impermeable PI. Western blot analysis was used to determine the protein expressions of TRPC6 and caspase-3. The involvement of TRPC6 was tested via RNAi against TRPC6.

RESULTS: OGD-induced neuronal death was decreased by tetramethylpyrazine in a concentration-dependent manner. The expression of TRPC6 protein was decreased by OGD. Furthermore, downregulating TRPC6 by RNA interfering mimicked the effect of OGD in neuronal death. Tetramethylpyrazine attenuated OGD-induced TRPC6 downregulation in a tetramethylpyrazine concentration-dependent manner. However, these effects of tetramethylpyrazine on attenuating OGD-induced neuronal death were abolished by TRPC6 RNAi.

CONCLUSIONS: Tetramethylpyrazine can protect neurons from oxygen-glucose deprivation-induced death, possibly via TRPC6.

Keywords: Niemann-Pick Disease, Type A, NK Cell Lectin-Like Receptor Subfamily C, Satellite Cells, Perineuronal