Hypoxic ischemic brain injury: animal models reveal new mechanisms of melatonin-mediated neuroprotection

References

Alawieh, A.M., Langley, E.F., Feng, W., Spiotta, A.M., and Tomlinson, S. (2020). Complement-dependent synaptic uptake and cognitive decline after stroke and reperfusion therapy. J. Neurosci. 40: 4042–4058, https://doi.org/10.1523/jneurosci.2462-19.2020.Search in Google Scholar PubMed PubMed Central

Alawieh, A., Elvington, A., Zhu, H., Yu, J., Kindy, M.S., Atkinson, C., and Tomlinson, S. (2015). Modulation of post-stroke degenerative and regenerative processes and subacute protection by site-targeted inhibition of the alternative pathway of complement. J. Neuroinflammation 12: 247, https://doi.org/10.1186/s12974-015-0464-8.Search in Google Scholar PubMed PubMed Central

Anrather, J. and Iadecola, C. (2016). Inflammation and stroke: an overview. Neurotherapeutics 13: 661–670, https://doi.org/10.1007/s13311-016-0483-x.Search in Google Scholar PubMed PubMed Central

Arneson, K.O. and Roberts, L.J. (2007). Measurement of products of docosahexaenoic acid peroxidation, neuroprostanes, and neurofurans. Methods Enzymol. 433: 127–143, https://doi.org/10.1016/S0076-6879(07)33007-3.Search in Google Scholar PubMed

Balduini, W., Weiss, M.D., Carloni, S., Rocchi, M., Sura, L., Rossignol, C., Longini, M., Bazzini, F., Perrone, S., Ott, D., et al.. (2019). Melatonin pharmacokinetics and dose extrapolation after enteral infusion in neonates subjected to hypothermia. J. Pineal res. 66: e12565, https://doi.org/10.1111/jpi.12565.Search in Google Scholar PubMed

Berger, R. and Garnier, Y. (1999). Pathophysiology of perinatal brain damage. Brain Res. Rev. 30: 107–134, https://doi.org/10.1016/s0165-0173(99)00009-0.Search in Google Scholar PubMed

Bersani, I., Pluchinotta, F., Dotta, A., Savarese, I., Campi, F., Auriti, C., Chuklantseva, N., Piersigilli, F., Gazzolo, F., Varrica, A., et al.. (2020). Early predictors of perinatal brain damage: the role of neurobiomarkers. Clin. Chem. Lab. Med. 58: 471–486, https://doi.org/10.1515/cclm-2019-0725.Search in Google Scholar PubMed

Brzezinski, A. (1997). Melatonin in humans. N. Engl. J. Med. 336: 186–195, https://doi.org/10.1056/nejm199701163360306.Search in Google Scholar PubMed

Buonocore, G., Perrone, S., and Bracci, R. (2001). Free radicals and brain damage in the newborn. Biol. Neonate 79: 180–186, https://doi.org/10.1159/000047088.Search in Google Scholar PubMed

Buonocore, G., Perrone, S., Longini, M., Paffetti, P., Vezzosi, P., Gatti, M.G., and Bracci, R. (2003). Non protein bound iron as early predictive marker of neonatal brain damage. Brain 126: 1224–1230, https://doi.org/10.1093/brain/awg116.Search in Google Scholar PubMed

Burton, G.J. and Fowden, A.L. (2012). The placenta and developmental programming: balancing fetal nutrient demands with maternal resource allocation. Placenta 33(Suppl) S23–S27, https://doi.org/10.1016/j.placenta.2011.11.013.Search in Google Scholar PubMed

Bustelo, M., Barkhuizen, M., van den Hove, D.L.A., Steinbusch, H.W.M., Bruno, M.A., Loidl, C.F., and Gavilanes, A.W.D. (2020). Clinical implications of epigenetic dysregulation in perinatal hypoxic-ischemic brain damage. Front. Neurol. 11: 483, https://doi.org/10.3389/fneur.2020.00483.Search in Google Scholar PubMed PubMed Central

Campbell, G., Licht-Mayer, S., and Mahad, D. (2019). Targeting mitochondria to protect axons in progressive MS. Neurosci. Lett. 710: 134258, https://doi.org/10.1016/j.neulet.2019.05.012.Search in Google Scholar PubMed

Carloni, S., Favrais, G., Saliba, E., Albertini, M.C., Chalon, S., Longini, M., Gressens, P., Buonocore, G., and Balduini, W. (2016). Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress, autophagy, and miR-34a/silent information regulator 1 pathway. J. Pineal Res. 61: 370–380, https://doi.org/10.1111/jpi.12354.Search in Google Scholar PubMed

Carloni, S., Girelli, S., Scopa, C., Buonocore, G., Longini, M., and Balduini, W. (2010). Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy 6: 366–377, https://doi.org/10.4161/auto.6.3.11261.Search in Google Scholar PubMed

Carloni, S., Perrone, S., Buonocore, G., Longini, M., Proietti, F., and Balduini, W. (2008). Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J. Pineal Res. 44: 157–164, https://doi.org/10.1111/j.1600-079x.2007.00503.x.Search in Google Scholar

Carloni, S., Riparini, G., Buonocore, G., and Balduini, W. (2017). Rapid modulation of the silent information regulator 1 by melatonin after hypoxia-ischemia in the neonatal rat brain. J. Pineal Res. 63, https://doi.org/10.1111/jpi.12434.Search in Google Scholar PubMed

Chang, L., Zhou, G., Soufan, O., and Xia, J. (2020). miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Res. 48: W244–W251, https://doi.org/10.1093/nar/gkaa467.Search in Google Scholar PubMed PubMed Central

Chen, Y., Chu, J.M.T., Chang, R.C.C., and Wong, G.T.C. (2022). The complement system in the central nervous system: from neurodevelopment to neurodegeneration. Biomolecules 12: 337, https://doi.org/10.3390/biom12020337.Search in Google Scholar PubMed PubMed Central

Cho, K.H.T., Xu, B., Blenkiron, C., and Fraser, M. (2019). Emerging roles of miRNAs in brain development and perinatal brain injury. Front. Physiol. 10: 227, https://doi.org/10.3389/fphys.2019.00227.Search in Google Scholar PubMed PubMed Central

Chock, V.Y., Rao, A., and Van Meurs, K.P. (2023). Optimal neuromonitoring techniques in neonates with hypoxic ischemic encephalopathy. Front. Pediatr. 11: 1138062, https://doi.org/10.3389/fped.2023.1138062.Search in Google Scholar PubMed PubMed Central

Coulthard, L.G., Hawksworth, O.A., and Woodruff, T.M. (2018). Complement: the emerging architect of the developing brain. Trends Neurosci. 41: 373–384, https://doi.org/10.1016/j.tins.2018.03.009.Search in Google Scholar PubMed

Dammann, O. and Leviton, A. (1997). Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr. Res. 42: 1–8, https://doi.org/10.1203/00006450-199707000-00001.Search in Google Scholar PubMed

Deng, W.G., Tang, S.T., Tseng, H.P., and Wu, K.K. (2006). Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding. Blood 108: 518–524, https://doi.org/10.1182/blood-2005-09-3691.Search in Google Scholar PubMed PubMed Central

Dong, Y., Fan, C., Hu, W., Jiang, S., Ma, Z., Yan, X., Deng, C., Di, S., Xin, Z., Wu, G., et al.. (2016). Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling. J. Pineal Res. 60: 253–262, https://doi.org/10.1111/jpi.12300.Search in Google Scholar PubMed

Evans, P.J., Evans, R., Kovar, I.Z., Holton, A.F., and Halliwell, B. (1992). Bleomycin-detectable iron in the plasma of premature and full-term neonates. FEBS Lett. 303: 210–212, https://doi.org/10.1016/0014-5793(92)80521-h.Search in Google Scholar PubMed

Finder, M., Boylan, G.B., Twomey, D., Ahearne, C., Murray, D.M., and Hallberg, B. (2020). Two-year neurodevelopmental outcomes after mild hypoxic ischemic encephalopathy in the era of therapeutic hypothermia. JAMA Pediatr. 174: 48–55, https://doi.org/10.1001/jamapediatrics.2019.4011.Search in Google Scholar PubMed PubMed Central

García, J.A., Ortiz, F., Miana, J., Doerrier, C., Fernández-Ortiz, M., Rusanova, I., Escames, G., García, J.J, and Acuña-Castroviejo, D. (2017). Contribution of inducible and neuronal nitric oxide synthases to mitochondrial damage and melatonin rescue in LPS-treated mice. J. Physiol. Biochem. 73: 235–244, https://doi.org/10.1007/s13105-017-0548-2.Search in Google Scholar PubMed

Gasque, P., Dean, Y.D., McGreal, E.P., VanBeek, J., and Morgan, B.P. (2000). Complement components of the innate immune system in health and disease in the CNS. Immunopharmacology 49: 171–186, https://doi.org/10.1016/s0162-3109(00)80302-1.Search in Google Scholar PubMed

Graham, E.M., Everett, A.D., Delpech, J.C., and Northington, F.J. (2018). Blood biomarkers for evaluation of perinatal encephalopathy: state of the art. Curr. Opin. Pediatr. 30: 199–203, https://doi.org/10.1097/mop.0000000000000591.Search in Google Scholar PubMed PubMed Central

Green, E.A., Garrick, S.P., Peterson, B., Berger, P.J., Galinsky, R., Hunt, R.W., Cho, S.X., Bourke, J.E., Nold, M.F., and Nold-Petry, C.A. (2023). The role of the interleukin-1 family in complications of prematurity. Int. J. Mol. Sci. 24: 2795, https://doi.org/10.3390/ijms24032795.Search in Google Scholar PubMed PubMed Central

Hammond, T.R., Marsh, S.E., and Stevens, B. (2019). Immune signaling in neurodegeneration. Immunity 50: 955–974, https://doi.org/10.1016/j.immuni.2019.03.016.Search in Google Scholar PubMed PubMed Central

Hardeland, R. (2018). Melatonin and inflammation-story of a double-edged blade. J. Pineal Res. 65: e12525, https://doi.org/10.1111/jpi.12525.Search in Google Scholar PubMed

Jaworska, J., Zalewska, T., Sypecka, J., and Ziemka-Nalecz, M. (2019). Effect of the HDAC inhibitor, sodium butyrate, on neurogenesis in a rat model of neonatal hypoxia-ischemia: potential mechanism of action. Mol. Neurobiol. 56: 6341–6370, https://doi.org/10.1007/s12035-019-1518-1.Search in Google Scholar PubMed PubMed Central

Jaworska, J., Ziemka-Nalecz, M., Sypecka, J., and Zalewska, T. (2017). The potential neuroprotective role of a histone deacetylase inhibitor, sodium butyrate, after neonatal hypoxia-ischemia. J. Neuroinflammation 14: 34, https://doi.org/10.1186/s12974-017-0807-8.Search in Google Scholar PubMed PubMed Central

Jayaraj, R.L., Azimullah, S., Beiram, R., Jalal, F.Y., and Rosenberg, G.A. (2019). Neuroinflammation: friend and foe for ischemic stroke. J. Neuroinflammation 16: 142, https://doi.org/10.1186/s12974-019-1516-2.Search in Google Scholar PubMed PubMed Central

Lambeth, J.D. and Neish, A.S. (2014). Nox enzymes and new thinking on reactive oxygen: a double-edged sword revisited. Annu. Rev. Pathol. 9: 119–145, https://doi.org/10.1146/annurev-pathol-012513-104651.Search in Google Scholar PubMed

Lee, A.C., Kozuki, N., Blencowe, H., Vos, T., Bahalim, A., Darmstadt, G.L., Niermeyer, S., Ellis, M., Robertson, N.J., Cousens, S., et al.. (2013). Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr. Res. 74: 50–72, https://doi.org/10.1038/pr.2013.206.Search in Google Scholar PubMed PubMed Central

López, L.C., Escames, G., Tapias, V., Utrilla, P., León, J., and Acuña-Castroviejo, D. (2006). Identification of an inducible nitric oxide synthase in diaphragm mitochondria from septic mice: its relationship with mitochondrial dysfunction and prevention by melatonin. Int. J. Biochem. Cell Biol. 38: 267–278, https://doi.org/10.1016/j.biocel.2005.09.008.Search in Google Scholar PubMed

Ma, Q., Zhang, L., and Pearce, W.J. (2019). MicroRNAs in brain development and cerebrovascular pathophysiology. Am. J. Physiol. Cell Physiol. 317: C3–C19, https://doi.org/10.1152/ajpcell.00022.2019.Search in Google Scholar PubMed PubMed Central

Marzocchi, B., Perrone, S., Paffetti, P., Magi, B., Bini, L., Tani, C., Longini, M., and Buonocore, G. (2005). Nonprotein-bound iron and plasma protein oxidative stress at birth. Pediatr. Res. 58: 1295–1299, https://doi.org/10.1203/01.pdr.0000183658.17854.28.Search in Google Scholar PubMed

Mendoza, M.C., Er, E.E., and Blenis, J. (2011). The Ras-ERK and PI3K-mTOR pathways: crosstalk and compensation. Trends Biochem. Sci. 36: 320–328, https://doi.org/10.1016/j.tibs.2011.03.006.Search in Google Scholar PubMed PubMed Central

Michailidou, I., Vreijling, J., Rumpf, M., Loos, M., Koopmans, B., Vlek, N., Straat, N., Agaser, C., Kuipers, T.B., Mei, H., et al.. (2023). The systemic inhibition of the terminal complement system reduces neuroinflammation but does not improve motor function in mouse models of CMT1A with overexpressed PMP22. Curr. Opin. Neurobiol. 4: 100077, https://doi.org/10.1016/j.crneur.2023.100077.Search in Google Scholar PubMed PubMed Central

Milne, G.L., Yin, H., Brooks, J.D., Sanchez, S., Jackson Roberts, L.2nd, and Morrow, J.D. (2007). Quantification of F2-isoprostanes in biological fluids and tissues as a measure of oxidant stress. Meth. Enzymol. 433: 113–126, https://doi.org/10.1016/S0076-6879(07)33006-1.Search in Google Scholar PubMed

Mittal, M.K., Sun, G., and Baren, J.M. (2012). A clinical decision rule to identify infants with apparent life-threatening event who can be safely discharged from the emergency department. Pediatr. Emerg. Care 28: 599–605, https://doi.org/10.1097/pec.0b013e31825cf576.Search in Google Scholar PubMed

Moujalled, D., Strasser, A., and Liddell, J.R. (2021). Molecular mechanisms of cell death in neurological diseases. Cell Death Differ. 28: 2029–2044, https://doi.org/10.1038/s41418-021-00814-y.Search in Google Scholar PubMed PubMed Central

Myatt, L. (2006). Placental adaptive responses and fetal programming. Physiol. J. 572: 25–30, https://doi.org/10.1113/jphysiol.2006.104968.Search in Google Scholar PubMed PubMed Central

Nair, J. and Kumar, V.H.S. (2018). Current and emerging therapies in the management of hypoxic ischemic encephalopathy in neonates. Children 5: 99, https://doi.org/10.3390/children5070099.Search in Google Scholar PubMed PubMed Central

Napolitano, F. and Montuori, N. (2022). Role of plasminogen activation system in platelet pathophysiology: emerging concepts for translational applications. Int. J. Mol. Sci. 23: 6065, https://doi.org/10.3390/ijms23116065.Search in Google Scholar PubMed PubMed Central

Negro, S., Benders, M.J.N.L., Tataranno, M.L., Coviello, C., de Vries, L.S., van Bel, F., Groenendaal, F., Longini, M., Proietti, F., Belvisi, E., et al.. (2018). Early prediction of hypoxic-ischemic brain injury by a new panel of biomarkers in a population of term newborns. Oxid. Med. Cell. Longev. 76: 7608108, https://doi.org/10.1155/2018/7608108.Search in Google Scholar PubMed PubMed Central

Paprocka, J., Kijonka, M., Rzepka, B., and Sokół, M. (2019). Melatonin in hypoxic-ischemic brain injury in term and preterm babies. Int. J. Endocrinol. 96: 9626715, https://doi.org/10.1155/2019/9626715.Search in Google Scholar PubMed PubMed Central

Paskaloğlu, K., Sener, G., Kapucu, C., and Ayanoğlu-Dülger, G. (2004). Melatonin treatment protects against sepsis-induced functional and biochemical changes in rat ileum and urinary bladder. Life Sci. 74: 1093–1104, https://doi.org/10.1016/j.lfs.2003.07.038.Search in Google Scholar PubMed

Pearson, G., Robinson, F., Beers Gibson, T., Xu, B.E., Karandikar, M., Berman, K., and Cobb, M.H. (2001). Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr. Rev. 22: 153–183, https://doi.org/10.1210/er.22.2.153.Search in Google Scholar

Perianayagam, M.C., Oxenkrug, G.F., and Jaber, B.L. (2005). Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine. Ann. N. Y. Acad. Sci. 1053: 386–393, https://doi.org/10.1196/annals.1344.033.Search in Google Scholar

Perrone, S., Cannavò, L., Manti, S., Rullo, I., Buonocore, G., Esposito, S.M.R., and Gitto, E. (2022). Pediatric multisystem syndrome associated with SARS-CoV-2 (MIS-C): the interplay of oxidative stress and inflammation. Int. J. Mol. Sci. 23: 12836, https://doi.org/10.3390/ijms232112836.Search in Google Scholar PubMed PubMed Central

Perrone, S., Laschi, E., and Buonocore, G. (2019). Biomarkers of oxidative stress in the fetus and in the newborn. Free Radic. Biol. Med. 142: 23–31, https://doi.org/10.1016/j.freeradbiomed.2019.03.034.Search in Google Scholar PubMed

Perrone, S., Romeo, C., Marseglia, L., Manti, S., Rizzo, C., Carloni, S., Albertini, M.C., Balduini, W., Buonocore, G., Weiss, M.D., et al.. (2023a). Melatonin in newborn infants undergoing surgery: a pilot study on its effects on postoperative oxidative stress. Antioxidants 12: 563, https://doi.org/10.3390/antiox12030563.Search in Google Scholar PubMed PubMed Central

Perrone, S., Grassi, F., Caporilli, C., Boscarino, G., Carbone, G., Petrolini, C., Gambini, L.M., Di Peri, A., Moretti, S., Buonocore, G., et al.. (2023b). Brain damage in preterm and full-term neonates: serum biomarkers for the early diagnosis and intervention. Antioxidants 12: 309, https://doi.org/10.3390/antiox12020309.Search in Google Scholar PubMed PubMed Central

Perrone, S., Santacroce, A., Longini, M., Proietti, F., Bazzini, F., and Buonocore, G. (2018). The free radical diseases of prematurity: from cellular mechanisms to bedside. Oxid. Med. Cell. Longev. 74: 7483062, https://doi.org/10.1155/2018/7483062.Search in Google Scholar PubMed PubMed Central

Perrone, S., Santacroce, A., Picardi, A., and Buonocore, G. (2016a). Fetal programming and early identification of newborns at high risk of free radical-mediated diseases. World J. Clin. Pediatr. 5: 172–181, https://doi.org/10.5409/wjcp.v5.i2.172.Search in Google Scholar PubMed PubMed Central

Perrone, S., Tataranno, M.L., Negro, S., Longini, M., Toti, M.S., Alagna, M.G., Proietti, F., Bazzini, F., Toti, P., and Buonocore, G. (2016b). Placental histological examination and the relationship with oxidative stress in preterm infants. Placenta 46: 72–78, https://doi.org/10.1016/j.placenta.2016.08.084.Search in Google Scholar PubMed

Qin, C., Zhou, L.Q., Ma, X.T., Hu, Z.W., Yang, S., Chen, M., Bosco, D.B., Wu, L.J., and Tian, D.S. (2019). Dual functions of microglia in ischemic stroke. Neurosci. Bull. 35: 921–933, https://doi.org/10.1007/s12264-019-00388-3.Search in Google Scholar PubMed PubMed Central

Ricklin, D. and Pouw, R.B. (2021). Complement disease: out of the shadow into the spotlight. Semin. Immunopathol. 43: 755–756, https://doi.org/10.1007/s00281-021-00897-2.Search in Google Scholar PubMed PubMed Central

Saugstad, O.D. (2005). Oxidative stress in the newborn--a 30-year perspective. Neonatology 88: 228–236, https://doi.org/10.1159/000087586.Search in Google Scholar PubMed

Schleef, R.R., Bevilacqua, M.P., Sawdey, M., Gimbrone, M.A.Jr, and Loskutoff, D.J. (1988). Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J. Bio. Chem. 263: 5797–5803, https://doi.org/10.1016/s0021-9258(18)60636-2.Search in Google Scholar

Sekerdag, E., Solaroglu, I., and Gursoy-Ozdemir, Y. (2018). Cell death mechanisms in stroke and novel molecular and cellular treatment options. Curr. Neuropharm. 16: 1396–1415, https://doi.org/10.2174/1570159x16666180302115544.Search in Google Scholar PubMed PubMed Central

Shang, B., Shi, H., Wang, X., Guo, X., Wang, N., Wang, Y., and Dong, L. (2016). Protective effect of melatonin on myenteric neuron damage in experimental colitis in rats. Fundam. Clin. Pharmacol. 30: 117–127, https://doi.org/10.1111/fcp.12181.Search in Google Scholar PubMed

Signorini, C., Ciccoli, L., Leoncini, S., Carloni, S., Perrone, S., Comporti, M., Balduini, W., and Buonocore, G. (2009). Free iron, total F-isoprostanes and total F-neuroprostanes in a model of neonatal hypoxic-ischemic encephalopathy: neuroprotective effect of melatonin. J. Pineal res. 46: 148–154, https://doi.org/10.1111/j.1600-079x.2008.00639.x.Search in Google Scholar PubMed

Signorini, C., Perrone, S., Sgherri, C., Ciccoli, L., Buonocore, G., Leoncini, S., Rossi, V., Vecchio, D., and Comporti, M. (2008). Plasma esterified F2-isoprostanes and oxidative stress in newborns: role of nonprotein-bound iron. Pediatr. Res. 63: 287–291, https://doi.org/10.1203/pdr.0b013e318163a1fd.Search in Google Scholar PubMed

Singh, R.K., Kumar, S., Gautam, P.K., Tomar, M.S., Verma, P.K., Singh, S.P., Kumar, S., and Acharya, A. (2017). Protein kinase C-α and the regulation of diverse cell responses. Biomol. Concepts 8: 143–153, https://doi.org/10.1515/bmc-2017-0005.Search in Google Scholar PubMed

Solberg, R., Longini, M., Proietti, F., Vezzosi, P., Saugstad, O.D., and Buonocore, G. (2012). Resuscitation with supplementary oxygen induces oxidative injury in the cerebral cortex. Free Radic. Biol. Med. 53: 1061–1067, https://doi.org/10.1016/j.freeradbiomed.2012.07.022.Search in Google Scholar PubMed

Song, R., Ren, L., Ma, H., Hu, R., Gao, H., Wang, L., Chen, X., Zhao, Z., and Liu, J. (2016). Melatonin promotes diabetic wound healing in vitro by regulating keratinocyte activity. Am. J. Transl. Res. 8: 4682–4693.Search in Google Scholar

Statello, L., Guo, C.J., Chen, L.L., and Huarte, M. (2021). Gene regulation by long non-coding RNAs and its biological functions. Nat. Rev. Mol. 22: 96–118, https://doi.org/10.1038/s41580-020-00315-9.Search in Google Scholar PubMed PubMed Central

Tang, Y. and Le, W. (2016). Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 53: 1181–1194, https://doi.org/10.1007/s12035-014-9070-5.Search in Google Scholar PubMed

Tegla, C.A., Cudrici, C., Rus, V., Ito, T., Vlaicu, S., Singh, A., and Rus, H. (2009). Neuroprotective effects of the complement terminal pathway during demyelination: implications for oligodendrocyte survival. J. Neuroimmunol. 213: 3–11, https://doi.org/10.1016/j.jneuroim.2009.06.006.Search in Google Scholar PubMed PubMed Central

Veerhuis, R., Nielsen, H.M., and Tenner, A.J. (2011). Complement in the brain. Mol. Immunol. 48: 1592–1603, https://doi.org/10.1016/j.molimm.2011.04.003.Search in Google Scholar PubMed PubMed Central

Vento, M. (2014). Oxygen supplementation in the neonatal period: changing the paradigm. Neonatology 105: 323–331, https://doi.org/10.1159/000360646.Search in Google Scholar PubMed

Vergadi, E., Ieronymaki, E., Lyroni, K., Vaporidi, K., and Tsatsanis, C. (2017). Akt signaling pathway in macrophage activation and M1/M2 polarization. J. Immunol. 198: 1006–1014, https://doi.org/10.4049/jimmunol.1601515.Search in Google Scholar PubMed

Wang, X. (2009). The antiapoptotic activity of melatonin in neurodegenerative diseases. CNS Neurosci. Ther. 15: 345–357, https://doi.org/10.1111/j.1755-5949.2009.00105.x.Search in Google Scholar PubMed PubMed Central

Wang, Z., Lu, Y., and Han, J. (2012). Peripheral blood microRNAs: a novel tool for diagnosing disease? Intractable Rare Dis. Res. 1: 98–102, https://doi.org/10.5582/irdr.2012.v1.3.98.Search in Google Scholar PubMed PubMed Central

Weiss, M.D., Carloni, S., Vanzolini, T., Coppari, S., Balduini, W., Buonocore, G., Longini, M., Perrone, S., Sura, L., Mohammadi, A., et al.. (2022). Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive. J. Pineal res. 73: e12818, https://doi.org/10.1111/jpi.12818.Search in Google Scholar PubMed PubMed Central

Wu, L., Xiong, X., Wu, X., Ye, Y., Jian, Z., Zhi, Z., and Gu, L. (2020). Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front. Mol. Neurosci. 13: 28, https://doi.org/10.3389/fnmol.2020.00028.Search in Google Scholar PubMed PubMed Central

Xia, M.Z., Liang, Y.L., Wang, H., Chen, X., Huang, Y.Y., Zhang, Z.H., Chen, Y.H., Zhang, C., Zhao, M., Xu, D.X., et al.. (2012). Melatonin modulates TLR4-mediated inflammatory genes through MyD88- and TRIF-dependent signaling pathways in lipopolysaccharide-stimulated RAW264.7 cells. J. Pineal res. 53: 325–334, https://doi.org/10.1111/j.1600-079x.2012.01002.x.Search in Google Scholar PubMed

Yıldız, E.P., Ekici, B., and Tatlı, B. (2017). Neonatal hypoxic ischemic encephalopathy: an update on disease pathogenesis and treatment. Expert Rev. Neurother. 17: 449–459, https://doi.org/10.1080/14737175.2017.1259567.Search in Google Scholar PubMed

Yoon, B.H., Jun, J.K., Romero, R., Park, K.H., Gomez, R., Choi, J.H., and Kim, I.O. (1997). Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1β, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am. J. Obstet. Gynecol. 177: 19–26, https://doi.org/10.1016/s0002-9378(97)70432-0.Search in Google Scholar PubMed