Abstract
Intracerebral hemorrhage (ICH) in preterm infants is one of the major co-morbidities of preterm birth and is associated with long-term neurodevelopmental deficits. There are currently no widely accepted treatments to prevent ICH or therapies for the neurological sequelae. With studies broadening the scope of cell death, the newly defined concept of regulated cell death has enriched our understanding of the underlying mechanisms of secondary brain injury after ICH and has suggested potential interventions in preterm infants. In this review, we will summarize the current evidence for regulated cell death pathways in preterm infants after ICH, including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, and PANoptosis as well as several potential intervention strategies that may protect the immature brain from secondary injury after ICH through regulating regulated cell death.
Graphical Abstract
[http://dx.doi.org/10.1001/jama.2021.23580] [PMID: 35040888]
[http://dx.doi.org/10.3389/fneur.2022.853417] [PMID: 35386416]
[http://dx.doi.org/10.1038/s41582-020-00447-8] [PMID: 33504979]
[http://dx.doi.org/10.1177/0271678X221098811] [PMID: 35491813]
[http://dx.doi.org/10.1007/s40263-021-00817-w] [PMID: 33959935]
[http://dx.doi.org/10.1055/s-0029-1214237] [PMID: 19267317]
[http://dx.doi.org/10.1007/s13760-022-01889-1] [PMID: 35182373]
[http://dx.doi.org/10.1016/j.pediatrneurol.2005.08.011] [PMID: 16504792]
[http://dx.doi.org/10.1186/s12974-014-0200-9] [PMID: 25441622]
[http://dx.doi.org/10.1016/j.brainres.2015.12.060] [PMID: 26772987]
[http://dx.doi.org/10.1542/neo.20-11-e636] [PMID: 31676738]
[http://dx.doi.org/10.1007/s12975-021-00980-8]
[http://dx.doi.org/10.1186/s12964-021-00799-8] [PMID: 34922574]
[http://dx.doi.org/10.1186/s12974-019-1486-4] [PMID: 31174551]
[http://dx.doi.org/10.4103/1673-5374.331539] [PMID: 35017436]
[http://dx.doi.org/10.1038/jcbfm.2009.274] [PMID: 20068576]
[http://dx.doi.org/10.3389/fnins.2019.00115] [PMID: 30837832]
[http://dx.doi.org/10.1089/ars.2010.3581] [PMID: 20919934]
[http://dx.doi.org/10.1111/j.1750-3639.2005.tb00111.x] [PMID: 16389939]
[http://dx.doi.org/10.1038/sj.cdd.4401545] [PMID: 15592434]
[http://dx.doi.org/10.1523/JNEUROSCI.5832-08.2009] [PMID: 19244535]
[http://dx.doi.org/10.1038/jcbfm.2008.124] [PMID: 18985054]
[http://dx.doi.org/10.3389/fphys.2015.00039] [PMID: 25750627]
[http://dx.doi.org/10.1002/cptx.51] [PMID: 30040239]
[http://dx.doi.org/10.1038/cdd.2014.137] [PMID: 25236395]
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[http://dx.doi.org/10.1590/1519-6984.228437] [PMID: 33111928]
[http://dx.doi.org/10.1002/iub.432] [PMID: 21438113]
[http://dx.doi.org/10.1203/01.PDR.0000084114.83724.65] [PMID: 12867600]
[http://dx.doi.org/10.1515/jpm.2010.125] [PMID: 20954855]
[http://dx.doi.org/10.1038/nchembio711] [PMID: 16408008]
[http://dx.doi.org/10.1038/nrm3737] [PMID: 24452471]
[http://dx.doi.org/10.3389/fphar.2021.701564] [PMID: 34322024]
[http://dx.doi.org/10.1161/STROKEAHA.111.635672] [PMID: 22076006]
[http://dx.doi.org/10.1038/cddis.2017.58] [PMID: 28252651]
[http://dx.doi.org/10.1007/s11064-014-1510-0] [PMID: 25576092]
[http://dx.doi.org/10.1177/0271678X20973609] [PMID: 33210566]
[http://dx.doi.org/10.1161/STROKEAHA.117.019253] [PMID: 30355103]
[http://dx.doi.org/10.2147/NDT.S181074] [PMID: 30532542]
[http://dx.doi.org/10.3892/mmr.2021.12183] [PMID: 34080030]
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[http://dx.doi.org/10.1038/s41418-017-0012-4] [PMID: 29362479]
[http://dx.doi.org/10.1038/nrmicro2070] [PMID: 19148178]
[http://dx.doi.org/10.1038/s41392-021-00507-5] [PMID: 33776057]
[http://dx.doi.org/10.1038/nature22393] [PMID: 28459430]
[http://dx.doi.org/10.1002/ana.24070] [PMID: 24273204]
[http://dx.doi.org/10.1186/s12974-015-0409-2] [PMID: 26475134]
[http://dx.doi.org/10.1111/bph.14639] [PMID: 30811584]
[http://dx.doi.org/10.1161/STROKEAHA.120.033285] [PMID: 34719258]
[http://dx.doi.org/10.1016/j.bbi.2018.02.015] [PMID: 29499303]
[http://dx.doi.org/10.1523/JNEUROSCI.4329-15.2016] [PMID: 26985043]
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.043] [PMID: 30268886]
[http://dx.doi.org/10.1007/978-981-13-9589-5_2] [PMID: 31456203]
[http://dx.doi.org/10.1021/acschembio.5b00245] [PMID: 25965523]
[http://dx.doi.org/10.1080/10408398.2018.1529653] [PMID: 30614244]
[http://dx.doi.org/10.1007/s12035-018-1403-3] [PMID: 30406908]
[http://dx.doi.org/10.2147/NDT.S120496] [PMID: 28096675]
[http://dx.doi.org/10.1161/STROKEAHA.107.501213] [PMID: 18292378]
[http://dx.doi.org/10.1016/j.brainresbull.2019.08.013] [PMID: 31442590]
[http://dx.doi.org/10.1172/jci.insight.90777] [PMID: 28405617]
[http://dx.doi.org/10.1161/STROKEAHA.116.015609] [PMID: 28250197]
[http://dx.doi.org/10.1016/j.brainres.2018.09.012] [PMID: 30205109]
[http://dx.doi.org/10.1016/j.cell.2019.03.032] [PMID: 31056284]
[http://dx.doi.org/10.1002/ana.25356] [PMID: 30294906]
[http://dx.doi.org/10.3389/fneur.2021.763419] [PMID: 34867747]
[http://dx.doi.org/10.1203/00006450-200102000-00013] [PMID: 11158515]
[http://dx.doi.org/10.1016/j.clp.2009.07.014] [PMID: 19944833]
[http://dx.doi.org/10.1227/NEU.0000000000000524] [PMID: 25121790]
[http://dx.doi.org/10.1203/00006450-200208000-00013] [PMID: 12149498]
[http://dx.doi.org/10.3389/fncel.2020.00231] [PMID: 32848622]
[http://dx.doi.org/10.1016/j.biopha.2018.05.007] [PMID: 29800913]
[http://dx.doi.org/10.4161/15548627.2014.984267] [PMID: 25484070]
[http://dx.doi.org/10.1089/ars.2013.5371] [PMID: 23725295]
[http://dx.doi.org/10.1042/EBC20170035] [PMID: 29233872]
[http://dx.doi.org/10.1038/s41418-018-0252-y] [PMID: 30568239]
[http://dx.doi.org/10.1038/nrm2529] [PMID: 18971948]
[http://dx.doi.org/10.1097/MD.0000000000017130] [PMID: 31574813]
[http://dx.doi.org/10.1007/s12640-020-00275-0] [PMID: 32840757]
[http://dx.doi.org/10.1016/j.neuint.2016.03.004] [PMID: 26964766]
[http://dx.doi.org/10.1007/s11064-021-03477-w] [PMID: 34743269]
[http://dx.doi.org/10.1111/cns.12703] [PMID: 28544790]
[http://dx.doi.org/10.1016/j.brainres.2011.09.062] [PMID: 22015349]
[http://dx.doi.org/10.4049/immunohorizons.2100059] [PMID: 34290111]
[http://dx.doi.org/10.1016/j.cell.2020.11.025] [PMID: 33278357]
[http://dx.doi.org/10.4103/1673-5374.346545] [PMID: 35900430]
[http://dx.doi.org/10.1097/CM9.0000000000002010] [PMID: 35261352]
[http://dx.doi.org/10.3389/fcimb.2020.00238] [PMID: 32582562]
[http://dx.doi.org/10.3389/fncel.2022.799753] [PMID: 35185473]
[http://dx.doi.org/10.1007/s12035-016-9947-6] [PMID: 27405469]
[http://dx.doi.org/10.1007/s12031-013-0132-3] [PMID: 24122153]
[http://dx.doi.org/10.1016/j.ceb.2020.02.004] [PMID: 32163825]
[http://dx.doi.org/10.1038/s41586-019-1770-6] [PMID: 31748744]
[http://dx.doi.org/10.1016/j.redox.2022.102232] [PMID: 35101798]
[http://dx.doi.org/10.1515/jpm-2020-0331] [PMID: 33735943]
[http://dx.doi.org/10.1016/j.euroneuro.2016.11.012] [PMID: 27919523]
[http://dx.doi.org/10.1016/j.brainres.2014.10.046] [PMID: 25451129]
[http://dx.doi.org/10.1007/s12035-015-9154-x] [PMID: 25833102]
[http://dx.doi.org/10.1016/j.jns.2016.10.025] [PMID: 27871457]
[http://dx.doi.org/10.1007/s00415-018-8935-3] [PMID: 29948247]
[http://dx.doi.org/10.1161/STROKEAHA.114.005079] [PMID: 24947291]
[http://dx.doi.org/10.1016/S1474-4422(19)30069-9] [PMID: 30898550]
[http://dx.doi.org/10.18632/aging.202457] [PMID: 33503014]
[http://dx.doi.org/10.1007/s10753-020-01270-5] [PMID: 32705396]
[http://dx.doi.org/10.1007/s12975-017-0559-x] [PMID: 28766251]
[http://dx.doi.org/10.1007/978-3-7091-0693-8_34] [PMID: 21725756]
[http://dx.doi.org/10.1080/14737175.2019.1555474] [PMID: 30560703]
[http://dx.doi.org/10.1002/jnr.24548] [PMID: 31797400]
[http://dx.doi.org/10.1186/s12929-021-00725-7] [PMID: 33849537]
[http://dx.doi.org/10.1002/glia.23919] [PMID: 33045105]
[http://dx.doi.org/10.1111/jnc.15267] [PMID: 33314066]
[http://dx.doi.org/10.1002/sctm.17-0219] [PMID: 30133179]
[http://dx.doi.org/10.1002/14651858.CD013201.pub2]
[http://dx.doi.org/10.1159/000511262] [PMID: 33113526]
[http://dx.doi.org/10.1542/peds.2008-3553] [PMID: 19651565]
[http://dx.doi.org/10.1016/j.jpeds.2015.02.052] [PMID: 25863661]
[http://dx.doi.org/10.1002/ana.24677] [PMID: 27130143]
[http://dx.doi.org/10.1016/j.clp.2015.04.004] [PMID: 26250911]
[http://dx.doi.org/10.1056/NEJMoa1907423] [PMID: 31940698]
[http://dx.doi.org/10.1001/jama.2016.5504] [PMID: 27187300]
[http://dx.doi.org/10.1016/j.bbrc.2018.04.171] [PMID: 29698679]
[http://dx.doi.org/10.2147/IJN.S293681] [PMID: 33574665]
[http://dx.doi.org/10.1124/jpet.116.238824] [PMID: 28035009]
[http://dx.doi.org/10.1007/s13311-021-01111-9] [PMID: 34498224]
[http://dx.doi.org/10.1016/j.intimp.2019.105887] [PMID: 31536904]
[http://dx.doi.org/10.1016/j.intimp.2019.106141] [PMID: 31982825]