• ISSN 1674-8301
  • CN 32-1810/R
Volume 35 Issue 6
Nov.  2021
Turn off MathJax
Article Contents
Xue Geng, Meng Wang, Yunjun Leng, Lin Li, Haiyuan Yang, Yifan Dai, Ying Wang. Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation[J]. The Journal of Biomedical Research, 2021, 35(6): 474-490. doi: 10.7555/JBR.35.20210107
Citation: Xue Geng, Meng Wang, Yunjun Leng, Lin Li, Haiyuan Yang, Yifan Dai, Ying Wang. Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation[J]. The Journal of Biomedical Research, 2021, 35(6): 474-490. doi: 10.7555/JBR.35.20210107

Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation

doi: 10.7555/JBR.35.20210107
More Information
  • Corresponding author: Ying Wang, Haiyuan Yang, and Yifan Dai, Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, China. Tel/Fax: +86-25-86869477, E-mails: ywang@njmu.edu.cn, hyyang@njmu.edu.cn, and daiyifan@njmu.edu.cn; 
  • Received: 2021-07-02
  • Revised: 2021-07-27
  • Accepted: 2021-08-06
  • Published: 2021-09-30
  • Issue Date: 2021-11-28
  • Acute hypoxic-ischemic brain damage (HIBD) mainly occurs in adults as a result of perioperative cardiac arrest and asphyxia. The benefits of n-3 polyunsaturated fatty acids (n-3 PUFAs) in maintaining brain growth and development are well documented. However, possible protective targets and underlying mechanisms of mfat-1 mice on HIBD require further investigation. The mfat-1 transgenic mice exhibited protective effects on HIBD, as indicated by reduced infarct range and improved neurobehavioral defects. RNA-seq analysis showed that multiple pathways and targets were involved in this process, with the anti-inflammatory pathway as the most significant. This study has shown for the first time that mfat-1 has protective effects on HIBD in mice. Activation of a G protein-coupled receptor 120 (GPR120)-related anti-inflammatory pathway may be associated with perioperative and postoperative complications, thus innovating clinical intervention strategy may potentially benefit patients with HIBD.

     

  • loading
  • [1]
    Hou K, Li G, Zhao J, et al. Correction to: bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway[J]. J Neuroinflammation, 2020, 17(1): 203. doi: 10.1186/s12974-020-01872-8
    [2]
    Jiao M, Li X, Chen L, et al. Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury[J]. J Neuroinflammation, 2020, 17(1): 251. doi: 10.1186/s12974-020-01932-z
    [3]
    Grau AJ, Eicke M, Burmeister C, et al. Risk of ischemic stroke and transient ischemic attack is increased up to 90 days after non-carotid and non-cardiac surgery[J]. Cerebrovasc Dis, 2017, 43(5-6): 242–249. doi: 10.1159/000460827
    [4]
    Selim M. Perioperative stroke[J]. N Engl J Med, 2007, 356: 706–713. doi: 10.1056/NEJMra062668
    [5]
    Yu S, Li P. Cognitive declines after perioperative covert stroke: Recent advances and perspectives[J]. Curr Opin Anesthesiol, 2020, 33(5): 651–654. doi: 10.1097/ACO.0000000000000903
    [6]
    González-Nieto D, Fernández-Serra R, Pérez-Rigueiro J, et al. Biomaterials to neuroprotect the stroke brain: a large opportunity for narrow time windows[J]. Cells, 2020, 9(5): 1074. doi: 10.3390/cells9051074
    [7]
    Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease[J]. Nat Rev Neurosci, 2014, 15(12): 771–785. doi: 10.1038/nrn3820
    [8]
    Wysoczański T, Sokoła-Wysoczańska E, Pękala J, et al. Omega-3 fatty acids and their role in central nervous system-a review[J]. Curr Med Chem, 2016, 23(8): 816–831. doi: 10.2174/0929867323666160122114439
    [9]
    Saini RK, Keum YS. Omega-3 and omega-6 polyunsaturated fatty acids: Dietary sources, metabolism, and significance—a review[J]. Life Sci, 2018, 203: 255–267. doi: 10.1016/j.lfs.2018.04.049
    [10]
    Hu X, Zhang F, Leak RK, et al. Transgenic overproduction of omega-3 polyunsaturated fatty acids provides neuroprotection and enhances endogenous neurogenesis after stroke[J]. Curr Mol Med, 2013, 13(9): 1465–1473. doi: 10.2174/15665240113139990075
    [11]
    Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain[J]. Mol Neurobiol, 2011, 44(2): 203–215. doi: 10.1007/s12035-010-8162-0
    [12]
    Yehuda S. Polyunsaturated fatty acids as putative cognitive enhancers[J]. Med Hypotheses, 2012, 79(4): 456–461. doi: 10.1016/j.mehy.2012.06.021
    [13]
    Bilal S, Haworth O, Wu L, et al. Fat-1 transgenic mice with elevated omega-3 fatty acids are protected from allergic airway responses[J]. Biochim Biophys Acta, 2011, 1812(9): 1164–1169. doi: 10.1016/j.bbadis.2011.05.002
    [14]
    Yu J, Yang H, Fang B, et al. mfat-1 transgene protects cultured adult neural stem cells against cobalt chloride-mediated hypoxic injury by activating Nrf2/ARE pathways[J]. J Neurosci Res, 2018, 96(1): 87–102. doi: 10.1002/jnr.24096
    [15]
    Kang J, Wang J, Wu L, et al. Fat-1 mice convert n-6 to n-3 fatty acids[J]. Nature, 2004, 427(6974): 504. doi: 10.1038/427504a
    [16]
    Kang JX. Fat-1 transgenic mice: a new model for omega-3 research[J]. Prostaglandins Leukot Essent Fatty Acids, 2007, 77(5-6): 263–267. doi: 10.1016/j.plefa.2007.10.010
    [17]
    Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view[J]. Trends Neurosci, 1999, 22(9): 391–397. doi: 10.1016/S0166-2236(99)01401-0
    [18]
    Vannucci RC, Vannucci SJ. A model of perinatal hypoxic-ischemic brain damage[J]. Ann N Y Acad Sci, 1997, 835: 234–249. doi: 10.1111/j.1749-6632.1997.tb48634.x
    [19]
    Murden S, Borbélyová V, Laštůvka Z, et al. Gender differences involved in the pathophysiology of the perinatal hypoxic-ischemic damage[J]. Physiol Res, 2019, 68(S3): S207–S217. doi: 10.33549/physiolres.934356
    [20]
    Bibus D, Lands B. Balancing proportions of competing omega-3 and omega-6 highly unsaturated fatty acids (HUFA) in tissue lipids[J]. Prostaglandins Leukot Essent Fatty Acids, 2015, 99: 19–23. doi: 10.1016/j.plefa.2015.04.005
    [21]
    Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84–91. doi: 10.1161/01.STR.20.1.84
    [22]
    Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination[J]. Stroke, 1986, 17(3): 472–476. doi: 10.1161/01.STR.17.3.472
    [23]
    Enam SF, Kader SR, Bodkin N, et al. Evaluation of M2-like macrophage enrichment after diffuse traumatic brain injury through transient interleukin-4 expression from engineered mesenchymal stromal cells[J]. J Neuroinflammation, 2020, 17(1): 197. doi: 10.1186/s12974-020-01860-y
    [24]
    Stroobants S, Gantois I, Pooters T, et al. Increased gait variability in mice with small cerebellar cortex lesions and normal rotarod performance[J]. Behav Brain Res, 2013, 241: 32–37. doi: 10.1016/j.bbr.2012.11.034
    [25]
    Cui Q, Zhang YL, Ma YH, et al. A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke[J]. J Ethnopharmacol, 2020, 257: 112891. doi: 10.1016/j.jep.2020.112891
    [26]
    Zhang J, Ma Y, Jing L, et al. Synaptic remodeling and reduced expression of the transcription factors, HES1 and HES5, in the cortex neurons of cognitively impaired hyperhomocysteinemic mice[J]. Pathol Res Pract, 2020, 216(6): 152953. doi: 10.1016/j.prp.2020.152953
    [27]
    Wang Z, Zhou F, Dou Y, et al. Melatonin alleviates intracerebral hemorrhage-induced secondary brain injury in rats via suppressing apoptosis, inflammation, oxidative stress, DNA damage, and mitochondria injury[J]. Transl Stroke Res, 2018, 9(1): 74–91. doi: 10.1007/s12975-017-0559-x
    [28]
    Álvarez-Sabín J, Maisterra O, Santamarina E, et al. Factors influencing haemorrhagic transformation in ischaemic stroke[J]. Lancet Neurol, 2013, 12(7): 689–705. doi: 10.1016/S1474-4422(13)70055-3
    [29]
    Yuan Q, Li R, Yang H, et al. Effects of reperfusion on neuronal changes and macrophagic response after transient focal ischemia-reperfusion of brain in rats[J]. J West China Univ Med Sci, 1999, 30(2): 155–157, 137. https://pubmed.ncbi.nlm.nih.gov/12212045/
    [30]
    Wang Y, Dzyubenko E, Sanchez-Mendoza E, et al. Postacute delivery of GABAA α5 antagonist promotes postischemic neurological recovery and peri-infarct brain remodeling[J]. Stroke, 2018, 49(10): 2495–2503. doi: 10.1161/STROKEAHA.118.021378
    [31]
    Oh DY, Walenta E, Akiyama TE, et al. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice[J]. Nat Med, 2014, 20(8): 942–947. doi: 10.1038/nm.3614
    [32]
    Wang M, Zhang X, Ma L, et al. Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: a mechanism for hepatoprotective effect against alcoholic liver disease[J]. Biochim Biophys Acta, 2017, 1863(12): 3190–3201. doi: 10.1016/j.bbadis.2017.08.026
    [33]
    Wei T, Yang L, Guo F, et al. Activation of GPR120 in podocytes ameliorates kidney fibrosis and inflammation in diabetic nephropathy[J]. Acta Pharmacol Sin, 2021, 42(2): 252–263. doi: 10.1038/s41401-020-00520-4
    [34]
    Yin J, Li H, Meng C, et al. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway[J]. Int J Biochem Cell Biol, 2016, 75: 11–22. doi: 10.1016/j.biocel.2016.03.008
    [35]
    Ridder DA, Schwaninger M. TAK1 inhibition for treatment of cerebral ischemia[J]. Exp Neurol, 2013, 239: 68–72. doi: 10.1016/j.expneurol.2012.09.010
    [36]
    Wang R, Pu H, Ye Q, et al. Transforming growth factor beta-activated kinase 1–dependent microglial and macrophage responses aggravate long-term outcomes after ischemic stroke[J]. Stroke, 2020, 51(3): 975–985. doi: 10.1161/STROKEAHA.119.028398
    [37]
    Da Costa MAC, Gauer MF, Gomes RZ, et al. Risk factors for perioperative ischemic stroke in cardiac surgery[J]. Rev Bras Cir Cardiovasc, 2015, 30(3): 365–372. doi: 10.5935/1678-9741.20150032
    [38]
    Bhutta AT, Schmitz ML, Swearingen C, et al. Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: a pilot randomized, double-blind, placebo-controlled trial[J]. Pediatr Crit Care Med, 2012, 13(3): 328–337. doi: 10.1097/PCC.0b013e31822f18f9
    [39]
    Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: identifying novel targets for neuroprotection[J]. Prog Neurobiol, 2014, 115: 157–188. doi: 10.1016/j.pneurobio.2013.11.006
    [40]
    Mitchell SJ, Merry AF, Frampton C, et al. Cerebral protection by lidocaine during cardiac operations: a follow-up study[J]. Ann Thorac Surg, 2009, 87(3): 820–825. doi: 10.1016/j.athoracsur.2008.12.042
    [41]
    Hirayama Y, Koizumi S. Hypoxia-independent mechanisms of HIF-1α expression in astrocytes after ischemic preconditioning[J]. Glia, 2017, 65(3): 523–530. doi: 10.1002/glia.23109
    [42]
    Vetrovoy O, Sarieva K, Lomert E, et al. Pharmacological HIF1 inhibition eliminates downregulation of the pentose phosphate pathway and prevents neuronal apoptosis in rat hippocampus caused by severe hypoxia[J]. J Mol Neurosci, 2020, 70(5): 635–646. doi: 10.1007/s12031-019-01469-8
    [43]
    Dobrzyn A, Dobrzyn P, Lee SH, et al. Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing β-oxidation in skeletal muscle[J]. Am J Physiol Endocrinol Metab, 2005, 288(3): E599–E607. doi: 10.1152/ajpendo.00439.2004
    [44]
    Jin Q, Li R, Hu N, et al. DUSP1 alleviates cardiac ischemia/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways[J]. Redox Biol, 2018, 14: 576–587. doi: 10.1016/j.redox.2017.11.004
    [45]
    Nadjar Y, Triller A, Bessereau JL, et al. The Susd2 protein regulates neurite growth and excitatory synaptic density in hippocampal cultures[J]. Mol Cell Neurosci, 2015, 65: 82–91. doi: 10.1016/j.mcn.2015.02.007
    [46]
    Ren Z, Chen L, Wang Y, et al. Activation of the omega-3 fatty acid receptor GPR120 protects against focal cerebral ischemic injury by preventing inflammation and apoptosis in mice[J]. J Immunol, 2019, 202(3): 747–759. doi: 10.4049/jimmunol.1800637
    [47]
    Im DS. FFA4 (GPR120) as a fatty acid sensor involved in appetite control, insulin sensitivity and inflammation regulation[J]. Mol Aspects Med, 2018, 64: 92–108. doi: 10.1016/j.mam.2017.09.001
    [48]
    Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology[J]. Nature, 2014, 510(7503): 92–101. doi: 10.1038/nature13479
  • JBR-2021-0107-supplementary.pdf
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(10)

    Article Metrics

    Article views (302) PDF downloads(35) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return