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- W3022749755 abstract "The combination of tetramethylpyrazine (TMP) and borneol (BO) has shown promise for treatment of cerebral ischemia in clinical and experimental studies. However, the mechanism for the synergistic effect of these compounds is unclear. In this study, global cerebral ischemia-reperfusion (GCIR) was induced in rats that were subsequently treated with tetramethylpyrazine phosphate (TMPP) (13.3 mg/kg), BO (0.16 g/kg), or the combination TMPP + BO. Neuronal ultrastructure and intracellular calcium [Ca2+]i levels were evaluated in hypothalamus and striatum. Neuron autophagy was evaluated by expression of LC3 II/I, ULK1, Beclin1, BNIP3, mTOR, and pAMPK. Neuron apoptosis was examined via apoptosis index (AI) and expression of p53, Bcl-2, Bax, and caspase-3. Both monotherapies significantly improved neuronal ultrastructure, reduced numbers of apoptotic neurons and AI, attenuated [Ca2+]i overload, increased expression of pAMPK, ULK1, and LC3 II/I, and markedly reduced expression of mTOR, p53, and caspase-3 in hypothalamus and striatum. In hypothalamus, TMPP increased Bcl-2 expression and decreased Bax expression. In striatum, TMPP and BO increased Beclin1 expression while TMPP increased Bcl-2 expression and decreased Bax expression. TMPP + BO combination therapy enhanced expression of LC3 II/I, pAMPK, mTOR, and ULK1 in hypothalamus, and pAMPK, mTOR, ULK1, Beclin1, and Bax in striatum compared to the monotherapies. Combination therapy synergistically modulated p53 and adjusted Bcl-2 in striatum compared to TMPP and BO monotherapies, respectively. These results demonstrated a synergistic effect of TMPP + BO in protecting against hypothalamus and striatum in rats from ischemia-reperfusion injury and suggested that the mechanism involved shifting neurons from harmful apoptosis to protective autophagy and reducing neuronal [Ca2+]i." @default.
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- W3022749755 date "2017-01-01" @default.
- W3022749755 modified "2023-10-16" @default.
- W3022749755 title "Tetramethylpyrazine phosphate and borneol combination therapy synergistically attenuated ischemia-reperfusion injury of the hypothalamus and striatum via regulation of apoptosis and autophagy in a rat model." @default.
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