Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Metformin Ameliorates Neuronal Necroptosis after Intracerebral Hemorrhage by Activating AMPK

Author(s): Chenhan Lin , Kaichuang Yang, Guoqiang Zhang and Jun Yu*

Volume 18, Issue 3, 2021

Published on: 23 September, 2021

Page: [351 - 359] Pages: 9

DOI: 10.2174/1567202618666210923150251

Price: $65

conference banner
Abstract

Background: Intracerebral hemorrhage (ICH) is a major cause of death and disability globally. As a type of secondary injury after ICH, treatment for cell death can promote the recovery of neurological function.

Methods: Among all the cell death, neuronal necroptosis has recently been demonstrated of significance in the pathogenesis of ICH. However, the administration of drugs against necroptosis has many limitations.

Results: In the present study, we found that metformin, a first-line medication for the treatment of type 2 diabetes, can effectively inhibit neuronal necroptosis after ICH by activating the AMPK related pathway, thereby significantly improving neurological function scores and reducing brain edema.

Conclusion: These results will provide a new perspective for future research in necroptosis.

Keywords: ICH, necroptosis, metformin, AMPK, rotarod test, western blot analysis.

[1]
Collaborators GBDCoD. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1151-210.
[http://dx.doi.org/10.1016/S0140-6736(17)32152-9] [PMID: 28919116]
[2]
Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1211-59.
[http://dx.doi.org/10.1016/S0140-6736(17)32154-2] [PMID: 28919117]
[3]
Balami JS, Buchan AM. Complications of intracerebral haemorrhage. Lancet Neurol 2012; 11(1): 101-18.
[http://dx.doi.org/10.1016/S1474-4422(11)70264-2] [PMID: 22172625]
[4]
Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol 2012; 11(8): 720-31.
[http://dx.doi.org/10.1016/S1474-4422(12)70104-7] [PMID: 22698888]
[5]
Chu X, Wu X, Feng H, et al. Coupling between interleukin-1r1 and necrosome complex involves in hemin-induced neuronal necroptosis after intracranial hemorrhage. Stroke 2018; 49(10): 2473-82.
[http://dx.doi.org/10.1161/STROKEAHA.117.019253] [PMID: 30355103]
[6]
Linkermann A, Green DR. Necroptosis. N Engl J Med 2014; 370(5): 455-65.
[http://dx.doi.org/10.1056/NEJMra1310050] [PMID: 24476434]
[7]
Zille M, Karuppagounder SS, Chen Y, et al. Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis. Stroke 2017; 48(4): 1033-43.
[http://dx.doi.org/10.1161/STROKEAHA.116.015609] [PMID: 28250197]
[8]
Shen H, Liu C, Zhang D, et al. Role for RIP1 in mediating necroptosis in experimental intracerebral hemorrhage model both in vivo and in vitro. Cell Death Dis 2017; 8(3): e2641.
[http://dx.doi.org/10.1038/cddis.2017.58] [PMID: 28252651]
[9]
Chen Y, Zhang L, Yu H, et al. Necrostatin-1 improves long-term functional recovery through protecting oligodendrocyte precursor cells after transient focal cerebral ischemia in mice. Neuroscience 2018; 371: 229-41.
[http://dx.doi.org/10.1016/j.neuroscience.2017.12.007] [PMID: 29247776]
[10]
Silke J, Rickard JA, Gerlic M. The diverse role of RIP kinases in necroptosis and inflammation. Nat Immunol 2015; 16(7): 689-97.
[http://dx.doi.org/10.1038/ni.3206] [PMID: 26086143]
[11]
Mandal P, Berger SB, Pillay S, et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell 2014; 56(4): 481-95.
[http://dx.doi.org/10.1016/j.molcel.2014.10.021] [PMID: 25459880]
[12]
Kaiser WJ, Daley-Bauer LP, Thapa RJ, et al. RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc Natl Acad Sci USA 2014; 111(21): 7753-8.
[http://dx.doi.org/10.1073/pnas.1401857111] [PMID: 24821786]
[13]
Kaiser WJ, Sridharan H, Huang C, et al. Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J Biol Chem 2013; 288(43): 31268-79.
[http://dx.doi.org/10.1074/jbc.M113.462341] [PMID: 24019532]
[14]
Ramachandran A, McGill MR, Xie Y, Ni HM, Ding WX, Jaeschke H. Receptor interacting protein kinase 3 is a critical early mediator of acetaminophen-induced hepatocyte necrosis in mice. Hepatology 2013; 58(6): 2099-108.
[http://dx.doi.org/10.1002/hep.26547] [PMID: 23744808]
[15]
Li JX, Feng JM, Wang Y, et al. The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. Cell Death Dis 2014; 5: e1278.
[http://dx.doi.org/10.1038/cddis.2014.241] [PMID: 24901049]
[16]
Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2016; 164(11): 740-51.
[http://dx.doi.org/10.7326/M15-2650] [PMID: 27088241]
[17]
Liu Y, Lu Z, Cui M, Yang Q, Tang Y, Dong Q. Tissue kallikrein protects SH-SY5Y neuronal cells against oxygen and glucose deprivation-induced injury through bradykinin B2 receptor-dependent regulation of autophagy induction. J Neurochem 2016; 139(2): 208-20.
[http://dx.doi.org/10.1111/jnc.13690] [PMID: 27248356]
[18]
Le DT, Jung S, Quynh NTN, et al. Inhibitory role of AMP-activated protein kinase in necroptosis of HCT116 colon cancer cells with p53 null mutation under nutrient starvation. Int J Oncol 2019; 54(2): 702-12.
[PMID: 30431068]
[19]
Wang YS, Yu P, Wang Y, et al. AMP-activated protein kinase protects against necroptosis via regulation of Keap1-PGAM5 complex. Int J Cardiol 2018; 259: 153-62.
[http://dx.doi.org/10.1016/j.ijcard.2018.01.036] [PMID: 29579593]
[20]
Rynkowski MA, Kim GH, Komotar RJ, et al. A mouse model of intracerebral hemorrhage using autologous blood infusion. Nat Protoc 2008; 3(1): 122-8.
[http://dx.doi.org/10.1038/nprot.2007.513] [PMID: 18193028]
[21]
Wu H, Wu T, Han X, et al. Cerebroprotection by the neuronal PGE2 receptor EP2 after intracerebral hemorrhage in middle-aged mice. J Cereb Blood Flow Metab 2017; 37(1): 39-51.
[http://dx.doi.org/10.1177/0271678X15625351] [PMID: 26746866]
[22]
Liu X, Liu J, Zhao S, et al. Interleukin-4 is essential for microglia/macrophage m2 polarization and long-term recovery after cerebral ischemia. Stroke 2016; 47(2): 498-504.
[http://dx.doi.org/10.1161/STROKEAHA.115.012079] [PMID: 26732561]
[23]
Shi L, Liang F, Zheng J, et al. Melatonin regulates apoptosis and autophagy via ros-mst1 pathway in subarachnoid hemorrhage. Front Mol Neurosci 2018; 11: 93.
[http://dx.doi.org/10.3389/fnmol.2018.00093] [PMID: 29632474]
[24]
Yan Q, Han C, Wang G, Waddington JL, Zheng L, Zhen X. Activation of ampk/mtorc1-mediated autophagy by metformin reverses clk1 deficiency-sensitized dopaminergic neuronal death. Mol Pharmacol 2017; 92(6): 640-52.
[http://dx.doi.org/10.1124/mol.117.109512] [PMID: 29025968]
[25]
Popp-Sennewald G. Nursing academy agnes karll. Assessment of resources and developmental tendencies. Krankenpflege (Frankf) 1988; 41(7-8): 322-3.
[PMID: 3138486]
[26]
Sembill JA, Huttner HB, Kuramatsu JB. Impact of recent studies for the treatment of intracerebral hemorrhage. Curr Neurol Neurosci Rep 2018; 18(10): 71.
[http://dx.doi.org/10.1007/s11910-018-0872-0] [PMID: 30128604]
[27]
Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol 2014; 115: 25-44.
[http://dx.doi.org/10.1016/j.pneurobio.2013.11.003] [PMID: 24291544]
[28]
Jiang B, Li L, Chen Q, et al. Role of glibenclamide in brain injury after intracerebral hemorrhage. Transl Stroke Res 2017; 8(2): 183-93.
[http://dx.doi.org/10.1007/s12975-016-0506-2] [PMID: 27807801]
[29]
Su X, Wang H, Kang D, et al. Necrostatin-1 ameliorates intracerebral hemorrhage-induced brain injury in mice through inhibiting RIP1/RIP3 pathway. Neurochem Res 2015; 40(4): 643-50.
[http://dx.doi.org/10.1007/s11064-014-1510-0] [PMID: 25576092]
[30]
Jouan-Lanhouet S, Riquet F, Duprez L, Vanden Berghe T, Takahashi N, Vandenabeele P. Necroptosis, in vivo detection in experimental disease models. Semin Cell Dev Biol 2014; 35: 2-13.
[http://dx.doi.org/10.1016/j.semcdb.2014.08.010] [PMID: 25160988]
[31]
Oliveira SR, Amaral JD, Rodrigues CMP. Mechanism and disease implications of necroptosis and neuronal inflammation. Cell Death Dis 2018; 9(9): 903.
[http://dx.doi.org/10.1038/s41419-018-0872-7] [PMID: 30185777]
[32]
Zhu K, Liang W, Ma Z, et al. Necroptosis promotes cell-autonomous activation of proinflammatory cytokine gene expression. Cell Death Dis 2018; 9(5): 500.
[http://dx.doi.org/10.1038/s41419-018-0524-y] [PMID: 29703889]
[33]
Qi B, Hu L, Zhu L, et al. Metformin attenuates neurological deficit after intracerebral hemorrhage by inhibiting apoptosis, oxidative stress and neuroinflammation in rats. Neurochem Res 2017; 42(10): 2912-20.
[http://dx.doi.org/10.1007/s11064-017-2322-9] [PMID: 28664399]
[34]
Pan Y, Sun X, Jiang L, et al. Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation. J Neuroinflammation 2016; 13(1): 294.
[http://dx.doi.org/10.1186/s12974-016-0754-9] [PMID: 27855689]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy