TRPM7 inhibitor carvacrol protects brain from neonatal hypoxic-ischemic injury
详细信息 查看全文
- 作者：Wenliang Chen ; Baofeng Xu ; Aijiao Xiao ; Ling Liu ; Xiaoyan Fang ; Rui Liu…
- 关键词：TRPM7 ; Neonatal hypoxic ; ischemic brain injury ; Neuroprotection ; Carvacrol
- 刊名：Molecular Brain
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：8
- 期：1
- 全文大小：3,092 KB
- 参考文献：1. Beilharz, EJ, Williams, CE, Dragunow, M, Sirimanne, ES, Gluckman, PD (1995) Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss. Brain Res Mol Brain Res 29: pp. 1-14 CrossRef
2. Dirnagl, U, Iadecola, C, Moskowitz, MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22: pp. 391-7 CrossRef
3. Legos, JJ, Tuma, RF, Barone, FC (2002) Pharmacological interventions for stroke: failures and future. Expert Opin Invest Drugs 11: pp. 603-14 CrossRef
4. Besancon, E, Guo, S, Lok, J, Tymianski, M, Lo, EH (2008) Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke. Trends Pharmacol Sci 29: pp. 268-75 CrossRef
5. Yang, XR, Lin, MJ, McIntosh, LS, Sham, JS (2006) Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol 290: pp. L1267-76 CrossRef
6. Aarts, M, Iihara, K, Wei, WL, Xiong, ZG, Arundine, M, Cerwinski, W (2003) A key role for TRPM7 channels in anoxic neuronal death. Cell 115: pp. 863-77 CrossRef
7. Jiang, H, Tian, SL, Zeng, Y, Li, LL, Shi, J (2008) TrkA pathway(s) is involved in regulation of TRPM7 expression in hippocampal neurons subjected to ischemic-reperfusion and oxygen-glucose deprivation. Brain Res Bull 76: pp. 124-30 CrossRef
8. Zhan, HQ, Li, PF, Li, SY, Yan, FL, Yang, J, Liu, RL (2014) Influence of lactuside B on the expression of AQP4 and TRPM7 mRNAs in the cerebral cortex after cerebral ischemia injury. Eur Rev Med Pharmacol Sci 18: pp. 1151-7
9. Zhang, Y, Zhou, L, Zhang, X, Bai, J, Shi, M, Zhao, G (2012) Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia. Neurol Sci : Off J Ital Neurol Soc Ital Soc Clin Neurophysiol 33: pp. 1125-31 CrossRef
10. Zhao, L, Wang, Y, Sun, N, Liu, X, Li, L, Shi, J (2007) Electroacupuncture regulates TRPM7 expression through the trkA/PI3K pathway after cerebral ischemia-reperfusion in rats. Life Sci 81: pp. 1211-22 CrossRef
11. Sun, HS, Jackson, MF, Martin, LJ, Jansen, K, Teves, L, Cui, H (2009) Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nat Neurosci 12: pp. 1300-7 CrossRef
12. Parnas, M, Peters, M, Dadon, D, Lev, S, Vertkin, I, Slutsky, I (2009) Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM7 channels. Cell Calcium 45: pp. 300-9 CrossRef
13. Yu, H, Zhang, ZL, Chen, J, Pei, A, Hua, F, Qian, X (2012) Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PLoS One 7: pp. e33584 CrossRef
14. Vannucci, RC (1990) Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage. Pediatr Res 27: pp. 317-26 CrossRef
15. Vannucci, RC (2000) Hypoxic-ischemic encephalopathy. Am J Perinatol 17: pp. 113-20 CrossRef
16. Pulera, MR, Adams, LM, Liu, H, Santos, DG, Nishimura, RN, Yang, F (1998) Apoptosis in a neonatal rat model of cerebral hypoxia-ischemia. Stroke: J Cereb Circ 29: pp. 2622-30
文摘
Background Our previous study found that suppression of TRPM7 reduced neuronal death in adult rat ischemic brain injury. It was reported that carvacrol blocked TRPM7 and attenuated brain injury in an adult rat MCAO model. The effects of carvacrol on neonatal stroke remain unknown. This study investigated the effects of carvacrol on neuronal injury and behavioral impairment after hypoxia-ischemia in neonatal mice and the potential signaling pathway underlying these effects. Results Carvacrol inhibited TRPM7 current in HEK293 cells over-expressing TRPM7 and TRPM7-like current in hippocampal neurons in a dose-dependent manner. Carvacrol (>200?μM) reduced OGD-induced neuronal injury in cortical neurons. 24?hours after HI, TRPM7 protein level in the ipsilateral hemisphere was significantly higher than in the contralateral hemisphere. Carvacrol (30 and 50?mg/kg) pre-treatment reduced brain infarct volume 24?hours after HI in a dose-dependent manner. Carvacrol pre-treatment also improved neurobehavioral outcomes. Furthermore, animals pre-treated with carvacrol had fewer TUNEL-positive cells in the brain compared to vehicle-treated animals 3?days after HI. Carvacrol pre-treatment also increased Bcl-2/Bax and p-Akt/t-Akt protein ratios and decreased cleaved caspase-3 protein expression 24?hours after HI. Conclusions Carvacrol pre-treatment protects against neonatal hypoxic-ischemic brain injury by reducing brain infarct volume, promoting pro-survival signaling and inhibiting pro-apoptotic signaling, as well as improving behavioral outcomes. The neuroprotective effect may be mediated by the inhibition of TRPM7 channel function. Carvacrol is a potential drug development target for the treatment of neonatal stroke.