Knockout of Alleviates Traumatic Brain Injury in Mice

Overview

Journal Neural Regen Res

Date 2022 Jul 28

PMID 35900429

Authors

Wei Wang

Qiu-Yuan Gong

Lin Cai

Yao Jing

Dian-Xu Yang

Fang Yuan

Hao Chen

Heng-Li Tian

Affiliations

Soon will be listed here.

Abstract

Sirtuin 2 (SIRT2) inhibition or Sirt2 knockout in animal models protects against the development of neurodegenerative diseases and cerebral ischemia. However, the role of SIRT2 in traumatic brain injury (TBI) remains unclear. In this study, we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema, attenuated disruption of the blood-brain barrier, decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, reduced the activity of the effector caspase-1, reduced neuroinflammation and neuronal pyroptosis, and improved neurological function. Knockout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis. Our findings suggest that knockout of Sirt2 is neuroprotective against TBI; therefore, Sirt2 could be a novel target for TBI treatment.

Citing Articles

SIRT2 Promotes NLRP3-Mediated Microglia Pyroptosis and Neuroinflammation via FOXO3a Pathway After Subarachnoid Hemorrhage.

Sun J, Sheng B, Gao S, Liu X, Cui Y, Peng Z J Inflamm Res. 2025; 17:11679-11698.

PMID: 39741753 PMC: 11687285. DOI: 10.2147/JIR.S487716.

Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.

He R, Liu Y, Fu W, He X, Liu S, Xiao D Mol Cancer. 2024; 23(1):267.

PMID: 39614268 PMC: 11606237. DOI: 10.1186/s12943-024-02172-y.

Neuroprotective potential for mitigating ischemia-reperfusion-induced damage.

Ye Z, Liu R, Wang H, Zuo A, Jin C, Wang N Neural Regen Res. 2024; 20(8):2199-2217.

PMID: 39104164 PMC: 11759025. DOI: 10.4103/NRR.NRR-D-23-01985.

Context-dependent role of sirtuin 2 in inflammation.

Sola-Sevilla N, Garmendia-Berges M, Mera-Delgado M, Puerta E Neural Regen Res. 2024; 20(3):682-694.

PMID: 38886935 PMC: 11433891. DOI: 10.4103/NRR.NRR-D-23-02063.

Cav3.2 channel regulates cerebral ischemia/reperfusion injury: a promising target for intervention.

Dai F, Hu C, Li X, Zhang Z, Wang H, Zhou W Neural Regen Res. 2024; 19(11):2480-2487.

PMID: 38526284 PMC: 11090426. DOI: 10.4103/1673-5374.390966.

References

Harting K, Knoll B . SIRT2-mediated protein deacetylation: An emerging key regulator in brain physiology and pathology. Eur J Cell Biol. 2009; 89(2-3):262-9. DOI: 10.1016/j.ejcb.2009.11.006. View

Ross J, Brough D, Gibson R, Loddick S, Rothwell N . A selective, non-peptide caspase-1 inhibitor, VRT-018858, markedly reduces brain damage induced by transient ischemia in the rat. Neuropharmacology. 2007; 53(5):638-42. DOI: 10.1016/j.neuropharm.2007.07.015. View

Yang Y, Wang H, Kouadir M, Song H, Shi F . Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019; 10(2):128. PMC: 6372664. DOI: 10.1038/s41419-019-1413-8. View

Kovacs S, Miao E . Gasdermins: Effectors of Pyroptosis. Trends Cell Biol. 2017; 27(9):673-684. PMC: 5565696. DOI: 10.1016/j.tcb.2017.05.005. View

Zhu W, Han B, Fan M, Wang N, Wang H, Zhu H . Oxidative stress increases the 17,20-lyase-catalyzing activity of adrenal P450c17 through p38α in the development of hyperandrogenism. Mol Cell Endocrinol. 2019; 484:25-33. DOI: 10.1016/j.mce.2019.01.020. View

Ma M, Wang J, Dhandapani K, Brann D . NADPH Oxidase 2 Regulates NLRP3 Inflammasome Activation in the Brain after Traumatic Brain Injury. Oxid Med Cell Longev. 2017; 2017:6057609. PMC: 5529650. DOI: 10.1155/2017/6057609. View

Sweeney M, Zhao Z, Montagne A, Nelson A, Zlokovic B . Blood-Brain Barrier: From Physiology to Disease and Back. Physiol Rev. 2018; 99(1):21-78. PMC: 6335099. DOI: 10.1152/physrev.00050.2017. View

Xu Z, Liu Y, Yang D, Yuan F, Ding J, Chen H . Sesamin protects SH-SY5Y cells against mechanical stretch injury and promoting cell survival. BMC Neurosci. 2017; 18(1):57. PMC: 5547510. DOI: 10.1186/s12868-017-0378-8. View

Bauernfeind F, Horvath G, Stutz A, Alnemri E, MacDonald K, Speert D . Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 2009; 183(2):787-91. PMC: 2824855. DOI: 10.4049/jimmunol.0901363. View

10.

Ding J, Wang K, Liu W, She Y, Sun Q, Shi J . Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016; 535(7610):111-6. DOI: 10.1038/nature18590. View

11.

Yang D, Jing Y, Liu Y, Xu Z, Yuan F, Wang M . Inhibition of Transient Receptor Potential Vanilloid 1 Attenuates Blood-Brain Barrier Disruption after Traumatic Brain Injury in Mice. J Neurotrauma. 2018; 36(8):1279-1290. DOI: 10.1089/neu.2018.5942. View

12.

Kerr N, Lee S, Perez-Barcena J, Crespi C, Ibanez J, Ross Bullock M . Inflammasome proteins as biomarkers of traumatic brain injury. PLoS One. 2019; 13(12):e0210128. PMC: 6312377. DOI: 10.1371/journal.pone.0210128. View

13.

Sun Z, Nyanzu M, Yang S, Zhu X, Wang K, Ru J . VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-B Pathways to Improve Functional Outcomes in TBI Mice. Oxid Med Cell Longev. 2020; 2020:7879629. PMC: 7181015. DOI: 10.1155/2020/7879629. View

14.

Li X, Wang B, Yang F, Chen L, You J . HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury. Neural Regen Res. 2021; 17(5):1096-1105. PMC: 8552838. DOI: 10.4103/1673-5374.322645. View

15.

Cookson B, Brennan M . Pro-inflammatory programmed cell death. Trends Microbiol. 2001; 9(3):113-4. DOI: 10.1016/s0966-842x(00)01936-3. View

16.

Morganti-Kossmann M, Semple B, Hellewell S, Bye N, Ziebell J . The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments. Acta Neuropathol. 2018; 137(5):731-755. DOI: 10.1007/s00401-018-1944-6. View

17.

Ma M, Wang J, Zhang Q, Wang R, Dhandapani K, Vadlamudi R . NADPH oxidase in brain injury and neurodegenerative disorders. Mol Neurodegener. 2017; 12(1):7. PMC: 5240251. DOI: 10.1186/s13024-017-0150-7. View

18.

Liu L, Arun A, Ellis L, Peritore C, Donmez G . SIRT2 enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via apoptotic pathway. Front Aging Neurosci. 2014; 6:184. PMC: 4127494. DOI: 10.3389/fnagi.2014.00184. View

19.

Saatman K, Feeko K, Pape R, Raghupathi R . Differential behavioral and histopathological responses to graded cortical impact injury in mice. J Neurotrauma. 2006; 23(8):1241-53. DOI: 10.1089/neu.2006.23.1241. View

20.

Liu W, Chen Y, Meng J, Wu M, Bi F, Chang C . Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo. J Neuroinflammation. 2018; 15(1):48. PMC: 5817788. DOI: 10.1186/s12974-018-1083-y. View