Effect of Gastrodin on Early Brain Injury and Neurological Outcome After Subarachnoid Hemorrhage in Rats
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摘要
Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage(SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin(100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAHinduced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca~(2+) overload.Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2–related factor2, heme oxygenase-1, phospho-Akt and B-cell lymphoma2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage(SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin(100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAHinduced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca~(2+) overload.Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2–related factor2, heme oxygenase-1, phospho-Akt and B-cell lymphoma2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage(SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin(100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAHinduced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca~(2+) overload.Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2–related factor2, heme oxygenase-1, phospho-Akt and B-cell lymphoma2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
引文
1.Chen S,Feng H,Sherchan P,Klebe D,Zhao G,Sun X,et al.Controversies and evolving new mechanisms in subarachnoid hemorrhage.Prog Neurobiol 2014,115:64-91.
2.Sehba FA,Hou J,Pluta RM,Zhang JH.The importance of early brain injury after subarachnoid hemorrhage.Prog Neurobiol2012,97:14-37.
3.Liu Y,Gao J,Peng M,Meng H,Ma H,Cai P,et al.A review on central nervous system effects of gastrodin.Front Pharmacol2018,9:24.
4.Lin LC,Chen YF,Tsai TR,Tsai TH.Analysis of brain distribution and biliary excretion of a nutrient supplement,gastrodin,in rat.Anal Chim Acta 2007,590:173-179.
5.Lin LC,Chen YF,Lee WC,Wu YT,Tsai TH.Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood,brain and bile by microdialysis coupled to LC-MS/MS.J Pharm Biomed Anal 2008,48:909-917.
6.Zeng X,Zhang S,Zhang L,Zhang K,Zheng X.A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro.Planta Med 2006,72:1359-1365.
7.Bie X,Chen Y,Han J,Dai H,Wan H,Zhao T.Effects of gastrodin on amino acids after cerebral ischemia-reperfusion injury in rat striatum.Asia Pac J Clin Nutr 2007,16 Suppl 1:305-308.
8.Peng Z,Wang S,Chen G,Cai M,Liu R,Deng J,et al.Gastrodin alleviates cerebral ischemic damage in mice by improving antioxidant and anti-inflammation activities and inhibiting apoptosis pathway.Neurochem Res 2015,40:661-673.
9.Liu B,Li F,Shi J,Yang D,Deng Y,Gong Q.Gastrodin ameliorates subacute phase cerebral ischemiareperfusion injury by inhibiting inflammation and apoptosis in rats.Mol Med Rep2016,14:4144-4152.
10.Sugawara T,Ayer R,Jadhav V,Zhang JH.A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model.J Neurosci Methods 2008,167:327-334.
11.Zhang ZY,Jiang M,Fang J,Yang MF,Zhang S,Yin YX,et al.Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood-brain barrier disruption through inhibition of inflammatory response and oxidative stress.Mol Neurobiol 2017,54:1-14.
12.Claassen J,Carhuapoma JR,Kreiter KT,Du EY,Connolly ES,Mayer SA.Global cerebral edema after subarachnoid hemorrhage:frequency,predictors,and impact on outcome.Stroke2002,33:1225-1232.
13.Zeng X,Zhang Y,Zhang S,Zheng X.A microdialysis study of effects of gastrodin on neurochemical changes in the ischemic/reperfused rat cerebral hippocampus.Biol Pharm Bull 2007,30:801-804.
14.Manaenko A,Chen H,Kammer J,Zhang JH,Tang J.Comparison Evans Blue injection routes:Intravenous versus intraperitoneal,for measurement of blood-brain barrier in a mice hemorrhage model.J Neurosci Methods 2011,195:206-210.
15.Zhang Z,Liu J,Fan C,Mao L,Xie R,Wang S,et al.The GluN1/GluN2B NMDA receptor and metabotropic glutamate receptor 1negative allosteric modulator has enhanced neuroprotection in a rat subarachnoid hemorrhage model.Exp Neurol 2018,301:13-25.
16.Wu CT,Wen LL,Wong CS,Tsai SY,Chan SM,Yeh CC,et al.Temporal changes in glutamate,glutamate transporters,basilar arteries wall thickness,and neuronal variability in an experimental rat model of subarachnoid hemorrhage.Anesth Analg 2011,112:666-673.
17.Boyko M,Melamed I,Gruenbaum BF,Gruenbaum SE,Ohayon S,Leibowitz A,et al.The effect of blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome in a rat model of subarachnoid hemorrhage.Neurotherapeutics 2012,9:649-657.
18.Kostandy BB.The role of glutamate in neuronal ischemic injury:the role of spark in fire.Neurol Sci 2012,33:223-237.
19.Hertz L,Peng L,Dienel GA.Energy metabolism in astrocytes:high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis.J Cereb Blood Flow Metab 2007,27:219-249.
20.Takeuchi H,Jin S,Wang J,Zhang G,Kawanokuchi J,Kuno R,et al.Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner.J Biol Chem 2006,281:21362-21368.
21.Murakami K,Koide M,Dumont TM,Russell SR,Tranmer BI,Wellman GC.Subarachnoid hemorrhage induces gliosis and increased expression of the pro-inflammatory cytokine high mobility group box 1 protein.Transl Stroke Res 2011,2:72-79.
22.Hanafy KA.The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage.J Neuroinflammation 2013,10:83.
23.Wang XL,Xing GH,Hong B,Li XM,Zou Y,Zhang XJ,et al.Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of Parkinson’s disease:involvement of ERK1/2-Nrf2 signaling pathway.Life Sci 2014,114:77-85.
24.Zhao X,Zou Y,Xu H,Fan L,Guo H,Li X,et al.Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway.Brain Res 2012,1482:13-21.
25.Hasegawa Y,Suzuki H,Sozen T,Altay O,Zhang JH.Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage.Acta Neurochir Suppl 2011,110:43-48.
26.Park S,Yamaguchi M,Zhou C,Calvert JW,Tang J,Zhang JH.Neurovascular protection reduces early brain injury after subarachnoid hemorrhage.Stroke 2004,35:2412-2417.
2.Sehba FA,Hou J,Pluta RM,Zhang JH.The importance of early brain injury after subarachnoid hemorrhage.Prog Neurobiol2012,97:14-37.
3.Liu Y,Gao J,Peng M,Meng H,Ma H,Cai P,et al.A review on central nervous system effects of gastrodin.Front Pharmacol2018,9:24.
4.Lin LC,Chen YF,Tsai TR,Tsai TH.Analysis of brain distribution and biliary excretion of a nutrient supplement,gastrodin,in rat.Anal Chim Acta 2007,590:173-179.
5.Lin LC,Chen YF,Lee WC,Wu YT,Tsai TH.Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood,brain and bile by microdialysis coupled to LC-MS/MS.J Pharm Biomed Anal 2008,48:909-917.
6.Zeng X,Zhang S,Zhang L,Zhang K,Zheng X.A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro.Planta Med 2006,72:1359-1365.
7.Bie X,Chen Y,Han J,Dai H,Wan H,Zhao T.Effects of gastrodin on amino acids after cerebral ischemia-reperfusion injury in rat striatum.Asia Pac J Clin Nutr 2007,16 Suppl 1:305-308.
8.Peng Z,Wang S,Chen G,Cai M,Liu R,Deng J,et al.Gastrodin alleviates cerebral ischemic damage in mice by improving antioxidant and anti-inflammation activities and inhibiting apoptosis pathway.Neurochem Res 2015,40:661-673.
9.Liu B,Li F,Shi J,Yang D,Deng Y,Gong Q.Gastrodin ameliorates subacute phase cerebral ischemiareperfusion injury by inhibiting inflammation and apoptosis in rats.Mol Med Rep2016,14:4144-4152.
10.Sugawara T,Ayer R,Jadhav V,Zhang JH.A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model.J Neurosci Methods 2008,167:327-334.
11.Zhang ZY,Jiang M,Fang J,Yang MF,Zhang S,Yin YX,et al.Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood-brain barrier disruption through inhibition of inflammatory response and oxidative stress.Mol Neurobiol 2017,54:1-14.
12.Claassen J,Carhuapoma JR,Kreiter KT,Du EY,Connolly ES,Mayer SA.Global cerebral edema after subarachnoid hemorrhage:frequency,predictors,and impact on outcome.Stroke2002,33:1225-1232.
13.Zeng X,Zhang Y,Zhang S,Zheng X.A microdialysis study of effects of gastrodin on neurochemical changes in the ischemic/reperfused rat cerebral hippocampus.Biol Pharm Bull 2007,30:801-804.
14.Manaenko A,Chen H,Kammer J,Zhang JH,Tang J.Comparison Evans Blue injection routes:Intravenous versus intraperitoneal,for measurement of blood-brain barrier in a mice hemorrhage model.J Neurosci Methods 2011,195:206-210.
15.Zhang Z,Liu J,Fan C,Mao L,Xie R,Wang S,et al.The GluN1/GluN2B NMDA receptor and metabotropic glutamate receptor 1negative allosteric modulator has enhanced neuroprotection in a rat subarachnoid hemorrhage model.Exp Neurol 2018,301:13-25.
16.Wu CT,Wen LL,Wong CS,Tsai SY,Chan SM,Yeh CC,et al.Temporal changes in glutamate,glutamate transporters,basilar arteries wall thickness,and neuronal variability in an experimental rat model of subarachnoid hemorrhage.Anesth Analg 2011,112:666-673.
17.Boyko M,Melamed I,Gruenbaum BF,Gruenbaum SE,Ohayon S,Leibowitz A,et al.The effect of blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome in a rat model of subarachnoid hemorrhage.Neurotherapeutics 2012,9:649-657.
18.Kostandy BB.The role of glutamate in neuronal ischemic injury:the role of spark in fire.Neurol Sci 2012,33:223-237.
19.Hertz L,Peng L,Dienel GA.Energy metabolism in astrocytes:high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis.J Cereb Blood Flow Metab 2007,27:219-249.
20.Takeuchi H,Jin S,Wang J,Zhang G,Kawanokuchi J,Kuno R,et al.Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner.J Biol Chem 2006,281:21362-21368.
21.Murakami K,Koide M,Dumont TM,Russell SR,Tranmer BI,Wellman GC.Subarachnoid hemorrhage induces gliosis and increased expression of the pro-inflammatory cytokine high mobility group box 1 protein.Transl Stroke Res 2011,2:72-79.
22.Hanafy KA.The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage.J Neuroinflammation 2013,10:83.
23.Wang XL,Xing GH,Hong B,Li XM,Zou Y,Zhang XJ,et al.Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of Parkinson’s disease:involvement of ERK1/2-Nrf2 signaling pathway.Life Sci 2014,114:77-85.
24.Zhao X,Zou Y,Xu H,Fan L,Guo H,Li X,et al.Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway.Brain Res 2012,1482:13-21.
25.Hasegawa Y,Suzuki H,Sozen T,Altay O,Zhang JH.Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage.Acta Neurochir Suppl 2011,110:43-48.
26.Park S,Yamaguchi M,Zhou C,Calvert JW,Tang J,Zhang JH.Neurovascular protection reduces early brain injury after subarachnoid hemorrhage.Stroke 2004,35:2412-2417.