Transient effect of melatonin treatment after neonatal hypoxic-ischemic brain injury in rats
Autoři:
Hester Rijkje Berger aff001; Axel K. G. Nyman aff003; Tora Sund Morken aff005; Marius Widerøe aff003
Působiště autorů:
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
aff001; Department of Pediatrics, St. Olav University Hospital, Trondheim, Norway
aff002; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
aff003; Department of Neurology, St. Olav University Hospital, Trondheim, Norway
aff004; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
aff005; Department of Ophthalmology, St. Olav University Hospital, Trondheim, Norway
aff006
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225788
Souhrn
Melatonin has potential neuroprotective capabilities after neonatal hypoxia-ischemia (HI), but long-term effects have not been investigated. We hypothesized that melatonin treatment directly after HI could protect against early and delayed brain injury. Unilateral HI brain injury was induced in postnatal day 7 rats. An intraperitoneal injection of either melatonin or vehicle was given at 0, 6 and 25 hours after hypoxia. In-vivo MRI was performed 1, 7, 20 and 43 days after HI, followed by histological analysis. Forelimb asymmetry and memory were assessed at 12–15 and at 36–43 days after HI. More melatonin treated than vehicle treated animals (54.5% vs 15.8%) developed a mild injury characterized by diffusion tensor values, brain volumes, histological scores and behavioral parameters closer to sham. However, on average, melatonin treatment resulted only in a tendency towards milder injury on T2-weighted MRI and apparent diffusion coefficient maps day 1 after HI, and not improved long-term outcome. These results indicate that the melatonin treatment regimen of 3 injections of 10 mg/kg within the first 25 hours only gave a transient and subtle neuroprotective effect, and may not have been sufficient to mitigate long-term brain injury development following HI.
Klíčová slova:
Brain damage – corpus callosum – Diffusion tensor imaging – Histology – Hypoxia – Magnetic resonance imaging – Medical hypoxia – Melatonin
Zdroje
1. Volpe JJ. Neurology of the Newborn. 5th ed. Philadelphia: Saunders Elsevier; 2008.
2. McQuillen PS, Ferriero DM. Selective vulnerability in the developing central nervous system. Pediatr Neurol. 2004;30: 227–235. doi: 10.1016/j.pediatrneurol.2003.10.001 15087099
3. Johnston M V, Fatemi A, Wilson MA, Northington F. Treatment advances in neonatal neuroprotection and neurointensive care. Lancet Neurol. 2011;10: 372–382. doi: 10.1016/S1474-4422(11)70016-3 21435600
4. Fleiss B, Gressens P. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy? Lancet Neurol. 2012;11: 556–566. doi: 10.1016/S1474-4422(12)70058-3 22608669
5. Osredkar D, Thoresen M, Maes E, Flatebø T, Elstad M, Sabir H. Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic–ischemic brain injury. Resuscitation. 2014;85: 567–572. doi: 10.1016/j.resuscitation.2013.12.006 24361672
6. Biran V, Decobert F, Bednarek N, Boizeau P, Benoist J-F, Claustrat B, et al. Melatonin Levels in Preterm and Term Infants and Their Mothers. Int J Mol Sci. Multidisciplinary Digital Publishing Institute (MDPI); 2019;20. doi: 10.3390/IJMS20092077 31035572
7. Biran V, Phan Duy A, Decobert F, Bednarek N, Alberti C, Baud O. Is melatonin ready to be used in preterm infants as a neuroprotectant? Dev Med Child Neurol. 2014;56: 717–23. doi: 10.1111/dmcn.12415 24575840
8. Colella M, Biran V, Baud O. Melatonin and the newborn brain. Early Hum Dev. Elsevier B.V.; 2016;102: 1–3. doi: 10.1016/j.earlhumdev.2016.09.001 27616207
9. Carloni S, Perrone S, Buonocore G, Longini M, Proietti F, Balduini W. Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J Pineal Res. 2008;44: 157–164. doi: 10.1111/j.1600-079X.2007.00503.x 18289167
10. Wang Z, Liu D, Zhan J, Xie K, Wang X, Xian X, et al. Melatonin improves short and long-term neurobehavioral deficits and attenuates hippocampal impairments after hypoxia in neonatal mice. Pharmacol Res. 2013;76: 84–97. doi: 10.1016/j.phrs.2013.07.008 23917218
11. Rice JE, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981;9: 131–141. doi: 10.1002/ana.410090206 7235629
12. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23: S208–S219. doi: 10.1016/j.neuroimage.2004.07.051 15501092
13. Woolrich MW, Jbabdi S, Patenaude B, Chappell M, Makni S, Behrens T, et al. Bayesian analysis of neuroimaging data in FSL. Neuroimage. 2009;45: S173–S186. doi: 10.1016/j.neuroimage.2008.10.055 19059349
14. Behrens TEJ, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S, et al. Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med. 2003;50: 1077–1088. doi: 10.1002/mrm.10609 14587019
15. van Velthoven CTJ, van de Looij Y, Kavelaars A, Zijlstra J, van Bel F, Huppi PS, et al. Mesenchymal stem cells restore cortical rewiring after neonatal ischemia in mice. Ann Neurol. 2012;71: 785–796. doi: 10.1002/ana.23543 22718545
16. Rojas JJ, Deniz BF, Miguel PM, Diaz R, Hermel E do E-S, Achaval M, et al. Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat. Exp Neurol. 2013;241: 25–33. doi: 10.1016/j.expneurol.2012.11.026 23219882
17. Antunes M, Biala G. The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process. 2012;13: 93–110. doi: 10.1007/s10339-011-0430-z 22160349
18. Swanson LW. Brain maps: Structure of the rat Brain. 3rd ed. San Diego: Elsevier Academic Press; 2004.
19. Wickham H. ggplot2: Elegant Graphics for Data Analysis [Internet]. Springer-Verlag New York; 2009. Available: http://ggplot2.org
20. Hagberg H, Bona E, Gilland E, Puka-Sundvall M. Hypoxia-ischaemia model in the 7-day-old rat: possibilities and shortcomings. Acta Paediatr Suppl. 1997;422: 85–88. doi: 10.1111/j.1651-2227.1997.tb18353.x 9298801
21. Carloni S, Riparini G, Buonocore G, Balduini W. Rapid modulation of the silent information regulator 1 by melatonin after hypoxia-ischemia in the neonatal rat brain. J Pineal Res. 2017;63: 1–11. doi: 10.1111/jpi.12434 28708259
22. Xu L-X, Lv Y, Li Y-H, Ding X, Wang Y, Han X, et al. Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins. BMC Pediatr. 2017;17: 90. doi: 10.1186/s12887-017-0824-x 28351378
23. Revuelta M, Arteaga O, Alvarez A, Martinez-Ibargüen A, Hilario E. Characterization of Gene Expression in the Rat Brainstem After Neonatal Hypoxic-Ischemic Injury and Antioxidant Treatment. Mol Neurobiol. 2017;54: 1129–1143. doi: 10.1007/s12035-016-9724-6 26809461
24. Berger HR, Nyman AKG, Morken TS, Vettukattil R, Brubakk AM, Widerøe M. Early metabolite changes after melatonin treatment in neonatal rats with hypoxic-ischemic brain injury studied by in-vivo 1H MR spectroscopy. PLoS One. 2017;12: 1–15. doi: 10.1371/journal.pone.0185202 28934366
25. Robertson NJ, Faulkner S, Fleiss B, Bainbridge A, Andorka C, Price D, et al. Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model. Brain. 2013;136: 90–105. doi: 10.1093/brain/aws285 23183236
26. Signorini C, Ciccoli L, Leoncini S, Carloni S, Perrone S, Comporti M, et al. Free iron, total F 2 -isoprostanes and total F 4 -neuroprostanes in a model of neonatal hypoxic-ischemic encephalopathy: neuroprotective effect of melatonin. J Pineal Res. 2009;46: 148–154. doi: 10.1111/j.1600-079X.2008.00639.x 19141088
27. Alonso-Alconada D, Alvarez A, Lacalle J, Hilario E. Histological study of the protective effect of melatonin on neural cells after neonatal hypoxia-ischemia. Histol Histopathol. 2012;27: 771–783. doi: 10.14670/HH-27.771 22473697
28. Villapol S, Fau S, Renolleau S, Biran V, Charriaut-Marlangue C, Baud O. Melatonin Promotes Myelination by Decreasing White Matter Inflammation After Neonatal Stroke. Pediatr Res. 2011;69: 51–55. doi: 10.1203/PDR.0b013e3181fcb40b 20856166
29. Meng S, Qiao MIN, Scobie K, Tomanek B, Tuor UI, West B, et al. Evolution of Magnetic Resonance Imaging Changes Associated with Cerebral Hypoxia-Ischemia and a Relatively Selective White Matter Injury in Neonatal Rats. Pediatr Res. 2006;59: 554–559. doi: 10.1203/01.pdr.0000203099.40643.84 16549528
30. Graham EM, Burd I, Everett AD, Northington FJ. Blood Biomarkers for Evaluation of Perinatal Encephalopathy. Front Pharmacol. 2016;7: 196. doi: 10.3389/fphar.2016.00196 27468268
31. Hill CA, Fitch RH. Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice. Neurol Res Int. Hindawi Limited; 2012;2012: 867531. doi: 10.1155/2012/867531 22474588
32. Tai S-H, Hung Y-C, Lee E-J, Lee A-C, Chen T-Y, Shen C-C, et al. Melatonin protects against transient focal cerebral ischemia in both reproductively active and estrogen-deficient female rats: the impact of circulating estrogen on its hormetic dose-response. J Pineal Res. 2011;50: 292–303. doi: 10.1111/j.1600-079X.2010.00839.x 21210839
33. Konkle ATM, McCarthy MM. Developmental Time Course of Estradiol, Testosterone, and Dihydrotestosterone Levels in Discrete Regions of Male and Female Rat Brain. Endocrinology. 2011;152: 223–235. doi: 10.1210/en.2010-0607 21068160
Článek vyšel v časopise
PLOS One
2019 Číslo 12
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Je libo čepici místo mozkového implantátu?
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- AI může chirurgům poskytnout cenná data i zpětnou vazbu v reálném čase
- Nová metoda odlišení nádorové tkáně může zpřesnit resekci glioblastomů
Nejčtenější v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy