Journals / Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi / 2026 / Cilt: 4 Sayı: 1

Examining the Effects of Oxygen Exposure on the Developing Brain Through Murine Models

Yenidoğan Rodent Modellerinde Hiperoksik Beyin Hasarının Değerlendirilmesi

Canberk Yılmaz(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İZMİR TIP FAKÜLTESİ)0000-0002-0049-7614
Defne Engür(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İZMİR TIP FAKÜLTESİ)0000-0003-0405-085X
Abdullah Kumral(DOKUZ EYLÜL ÜNİVERSİTESİ)0000-0003-0004-1761
Osman Yılmaz(DOKUZ EYLÜL ÜNİVERSİTESİ)0000-0001-7817-7576
Pages
15–25
Publication Date
2024-03-29
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Correlations between motor development, behavior, memory tests, and results of cellular/ molecular studies should be made and interpreted carefully.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Hyperoxia is one of the key players contributing preterm brain injury.
📊
Key Findings & Data:A model that is appropriate for the brain's developmental processes and accurately simulates the damage in humans should be utilized in studies on neonatal hyperoxic brain injury, and the right test should be chosen at the appropriate time.
💡
Conclusion & Impact:Correlations between motor development, behavior, memory tests, and results of cellular/ molecular studies should be made and interpreted carefully.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Beyin hasarı · davranış testleri · hiperoksi modeli

Abstract

Hyperoxia is one of the key players contributing preterm brain injury. Researchers typically use rodent models to pinpoint the underlying pathologic alterations in hyperoxic brain damage. When evaluating the neurological effects of neonatal hyperoxic brain injury in an experimental model, choosing the appropriate assessment techniques is crucial. The goal of this article is to review the behavioral and learning tests that can be used to determine the impact of hyperoxia on the developing brain. Injuries to the nervous system can be recovered very quickly in newborn rodents. Thus, the timing of evaluation tests are very critical. A model that is appropriate for the brain's developmental processes and accurately simulates the damage in humans should be utilized in studies on neonatal hyperoxic brain injury, and the right test should be chosen at the appropriate time. In the first twenty days, physical and motor development tests, and subsequent evaluation of damaged brain structures are relevant. The open field and forced swim tests can be used to assess the animal's locomotor activity and depressive condition, while the watermaze, passive avoidance and new object recognition tests can be used to assess cognitive abilities. In laboratory mice and rats, physical development and motor reflex development tests can be started right after birth, while learning and memory tests can be done from 4 weeks at the earliest. Correlations between motor development, behavior, memory tests, and results of cellular/ molecular studies should be made and interpreted carefully.

Özet

Hiperoksi, preterm beyin hasarına katkıda bulunan önemli postnatal faktörlerden biridir. Hiperoksinin neden preterm beyin dokusunda yol açtığı olduğu patolojik süreçlerin aydınlatılabilmesi için deneysel kemirgen modelleri sıklıkla kullanılmaktadır. Bu derleme, yenidoğan hiperoksik beyin hasarının değerlendirmesinde, araştırmacıların davranış ve öğrenme testleri ile ilgili seçimlerine ışık tutmayı hedeflemektedir. Yenidoğan kemirgen modellerinde, hayvanların nörolojik hasarlarından hızla iyileşme konusunda yüksek yeteneğe sahip olduğu göz ardı edilmemeli ve değerlendirme testlerinin yapılma zamanı iyi belirlenmelidir. Beynin gelişimsel süreçlerine uygun, insanlardaki hasarı daha iyi yansıtacak hayvan modeli kullanılmalı, doğru değerlendirme testi seçilmeli ve seçilen testler doğru zamanda uygulanmalıdır. Yaşamın ilk yirmi gününde fiziksel ve motor gelişim testleri kullanılmalı, daha sonraki süreçte beyin olgunlaşmasına paralel olarak davranış ve bellek testleri ile değerlendirilme yapılmalıdır. Lokomotor aktivite ve depresyon varlığı açısından açık alan testi, bilişsel işlevlerin değerlendirilmesi için yeni obje tanıma, su labirenti ve pasif kaçınma testleri seçilebilir. Motor gelişim, davranış ve bellek testleri, hücresel ve moleküler değişiklikler ile korele edilerek yorumlanmalıdır.

🔖

Cite This Article

Yılmaz, C., Engür, D., Kumral, A., Yılmaz, O. (2024). Examining the Effects of Oxygen Exposure on the Developing Brain Through Murine Models. Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi, Cilt: 4 Sayı: 1, 15–25. https://doi.org/10.5281/zenodo.10894221

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (51)

  1. Andresen, J. H., & Saugstad, O. D. (2020). Oxygen metabolism and oxygenation of the newborn. Seminars in Fetal & Neonatal Medicine, 25(2), 101078. https://doi.org/10.1016/j.siny.2020.101078
  2. Back, S. A., Luo, N. L., Borenstein, N. S., Levine, J. M., Volpe, J. J., & Kinney, H. C. (2001). Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury. The Journal of Neuroscience, 21(4), 1302–1312. https://doi.org/10.1523/JNEUROSCI.21-04-01302.2001
  3. Back, S. A., Riddle, A., & McClure, M. M. (2007). Maturation-dependent vulnerability of perinatal white matter in premature birth. Stroke, 38(2 Suppl), 724–730. https://doi.org/10.1161/01.STR.0000254729.27386.05
  4. Balasubramaniam, J., Xue, M., & Del Bigio, M. (2005). Long-term motor deficit following periventricular hemorrhage in neonatal rats: A potential model for human cerebral palsy. Journal of Cerebral Blood Flow & Metabolism, 25(1_suppl), S242–S242. https://doi.org/10.1038/sj.jcbfm.9591524.0242
  5. Bandstra, E. S., Morrow, C. E., Mansoor, E., & Accornero, V. H. (2010). Prenatal drug exposure: Infant and toddler outcomes. Journal of Addictive Diseases, 29(2), 245–258. https://doi.org/10.1080/10550881003684871
  6. Brehmer, F., Bendix, I., Prager, S., van de Looij, Y., Reinboth, B. S., Zimmermanns, J., Schlager, G. W., Brait, D., Sifringer, M., Endesfelder, S., Sizonenko, S., Mallard, C., Bührer, C., Felderhoff-Mueser, U., & Gerstner, B. (2012). Interaction of Inflammation and Hyperoxia in a Rat Model of Neonatal White Matter Damage. PLoS ONE, 7(11), e49023. https://doi.org/10.1371/journal.pone.0049023
  7. Cameron, N. M., Shahrokh, D., Del Corpo, A., Dhir, S. K., Szyf, M., Champagne, F. A., & Meaney, M. J. (2008). Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care. Journal of Neuroendocrinology, 20(6), 795–801. https://doi.org/10.1111/j.1365-2826.2008.01725.x
  8. Champagne, F. A. (2009). Nurturing nature: Social experiences and the brain. Journal of Neuroendocrinology, 21(10), 867–868. https://doi.org/10.1111/j.1365-2826.2009.01901.x
  9. Chawanpaiboon, S., Vogel, J. P., Moller, A.-B., Lumbiganon, P., Petzold, M., Hogan, D., Landoulsi, S., Jampathong, N., Kongwattanakul, K., Laopaiboon, M., Lewis, C., Rattanakanokchai, S., Teng, D. N., Thinkhamrop, J., Watananirun, K., Zhang, J., Zhou, W., & Gülmezoglu, A. M. (2019). Global, regional, and national estimates of levels of preterm birth in 2014: A systematic review and modelling analysis. The Lancet. Global Health, 7(1), e37–e46. https://doi.org/10.1016/S2214-109X(18)30451-0
  10. Clancy, B., Finlay, B. L., Darlington, R. B., & Anand, K. J. S. (2007). Extrapolating brain development from experimental species to humans. Neurotoxicology, 28(5), 931–937. https://doi.org/10.1016/j.neuro.2007.01.014
  11. Corti, S., Nizzardo, M., Nardini, M., Donadoni, C., Salani, S., Ronchi, D., Saladino, F., Bordoni, A., Fortunato, F., Del Bo, R., Papadimitriou, D., Locatelli, F., Menozzi, G., Strazzer, S., Bresolin, N., & Comi, G. P. (2008). Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy. The Journal of Clinical Investigation, 118(10), 3316–3330. https://doi.org/10.1172/JCI35432
  12. Dean, J. M., Moravec, M. D., Grafe, M., Abend, N., Ren, J., Gong, X., Volpe, J. J., Jensen, F. E., Hohimer, A. R., & Back, S. A. (2011). Strain-specific differences in perinatal rodent oligodendrocyte lineage progression and its correlation with human. Developmental Neuroscience, 33(3–4), 251–260. https://doi.org/10.1159/000327242
  13. DeSesso, J. M., Scialli, A. R., & Holson, J. F. (1999). Apparent lability of neural tube closure in laboratory animals and humans. American Journal of Medical Genetics, 87(2), 143–162. https://doi.org/10.1002/(sici)1096-8628(19991119)87:2 3.0.co;2-j
  14. Di Florio, D. N., Sin, J., Coronado, M. J., Atwal, P. S., & Fairweather, D. (2020). Sex differences in inflammation, redox biology, mitochondria and autoimmunity. Redox Biology, 31, 101482. https://doi.org/10.1016/j.redox.2020.101482
  15. Dobbing, J., & Sands, J. (1973). Quantitative growth and development of human brain. Archives of Disease in Childhood, 48(10), 757–767. https://doi.org/10.1136/adc.48.10.757
  16. Dobbing, J., & Sands, J. (1979). Comparative aspects of the brain growth spurt. Early Human Development, 3(1), 79–83. https://doi.org/10.1016/0378-3782(79)90022-7
  17. El-Khodor, B. F., Edgar, N., Chen, A., Winberg, M. L., Joyce, C., Brunner, D., Suárez-Fariñas, M., & Heyes, M. P. (2008). Identification of a battery of tests for drug candidate evaluation in the SMNDelta7 neonate model of spinal muscular atrophy. Experimental Neurology, 212(1), 29–43. https://doi.org/10.1016/j.expneurol.2008.02.025
  18. Eltokhi, A., Kurpiers, B., & Pitzer, C. (2020). Behavioral tests assessing neuropsychiatric phenotypes in adolescent mice reveal strain- and sex-specific effects. Scientific Reports, 10(1), 11263. https://doi.org/10.1038/s41598-020-67758-0
  19. Falsaperla, R., Giacchi, V., Saporito, M. A. N., Pavone, P., Puglisi, F., & Ruggieri, M. (2022). Pulse Oximetry Saturation (Spoxygen) Monitoring in the Neonatal Intensive Care Unit (NICU): The Challenge for Providers: A Systematic Review. Advances in Neonatal Care: Official Journal of the National Association of Neonatal Nurses, 22(3), 231–238. https://doi.org/10.1097/ANC.0000000000000914
  20. Farber, J. M., Shapiro, B. K., Palmer, F. B., & Capute, A. J. (1985). The diagnostic value of the neurodevelopmental examination. Clinical Pediatrics, 24(7), 367–372. https://doi.org/10.1177/000992288502400701
  21. Farrow, K. N., Lee, K. J., Perez, M., Schriewer, J. M., Wedgwood, S., Lakshminrusimha, S., Smith, C. L., Steinhorn, R. H., & Schumacker, P. T. (2012). Brief Hyperoxia Increases Mitochondrial Oxidation and Increases Phosphodiesterase 5 Activity in Fetal Pulmonary Artery Smooth Muscle Cells. Antioxidants & Redox Signaling, 17(3), 460–470. https://doi.org/10.1089/ars.2011.4184
  22. Feather-Schussler, D. N., & Ferguson, T. S. (2016). A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy. Journal of Visualized Experiments: JoVE, 117. https://doi.org/10.3791/53569
  23. Felderhoff-Mueser, U., Bittigau, P., Sifringer, M., Jarosz, B., Korobowicz, E., Mahler, L., Piening, T., Moysich, A., Grune, T., Thor, F., Heumann, R., Bührer, C., & Ikonomidou, C. (2004). Oxygen causes cell death in the developing brain. Neurobiology of Disease, 17(2), 273–282. https://doi.org/10.1016/j.nbd.2004.07.019
  24. Fox, W. M. (1965). Reflex-ontogeny and behavioural development of the mouse. Animal Behaviour, 13(2), 234–241. https://doi.org/10.1016/0003-3472(65)90041-2
  25. Gerstner, B., DeSilva, T. M., Genz, K., Armstrong, A., Brehmer, F., Neve, R. L., Felderhoff-Mueser, U., Volpe, J. J., & Rosenberg, P. A. (2008). Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter. The Journal of Neuroscience, 28(5), 1236–1245. https://doi.org/10.1523/JNEUROSCI.3213-07.2008
  26. Giusto, K., Wanczyk, H., Jensen, T., & Finck, C. (2021). Hyperoxia-induced bronchopulmonary dysplasia: Better models for better therapies. Disease Models & Mechanisms, 14(2), dmm047753. PubMed. https://doi.org/10.1242/dmm.047753
  27. Grondard, C., Biondi, O., Armand, A.-S., Lécolle, S., Della Gaspera, B., Pariset, C., Li, H., Gallien, C.-L., Vidal, P.-P., Chanoine, C., & Charbonnier, F. (2005). Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 25(33), 7615–7622. https://doi.org/10.1523/JNEUROSCI.1245-05.2005
  28. Hager, A. M., & Dringenberg, H. C. (2010). Training-induced plasticity in the visual cortex of adult rats following visual discrimination learning. Learning & Memory (Cold Spring Harbor, N.Y.), 17(8), 394–401. https://doi.org/10.1101/lm.1787110
  29. Heyser, C. J. (2003). Assessment of Developmental Milestones in Rodents. Current Protocols in Neuroscience, 25(1), 8.18.1-8.18.15. https://doi.org/10.1002/0471142301.ns0818s25
  30. Hill, J. M., Lim, M. A., & Stone, M. M. (2008). Developmental Milestones in the Newborn Mouse. In I. Gozes (Ed.), Neuropeptide Techniques (pp. 131–149). Humana Press. https://doi.org/10.1007/978-1-60327-099-1_10
  31. Kwak, D. J., Kwak, S. D., & Gauda, E. B. (2006). The effect of hyperoxia on reactive oxygen species (ROS) in rat petrosal ganglion neurons during development using organotypic slices. Pediatric Research, 60(4), 371–376. https://doi.org/10.1203/01.pdr.0000239817.39407.61
  32. Lubics, A., Reglodi, D., Tamás, A., Kiss, P., Szalai, M., Szalontay, L., & Lengvári, I. (2005). Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury. Behavioural Brain Research, 157(1), 157–165. https://doi.org/10.1016/j.bbr.2004.06.019
  33. Lueptow, L. M. (2017). Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. Journal of Visualized Experiments: JoVE, 126, 55718. https://doi.org/10.3791/55718
  34. Micili, S. C., Engür, D., Genc, S., Ercan, I., Soy, S., Baysal, B., & Kumral, A. (2020). Oxygen exposure in early life activates NLRP3 inflammasome in mouse brain. Neuroscience Letters, 738, 135389. https://doi.org/10.1016/j.neulet.2020.135389
  35. Perrone, S., Bracciali, C., Di Virgilio, N., & Buonocore, G. (2017). Oxygen Use in Neonatal Care: A Two-edged Sword. Frontiers in Pediatrics, 4, 143. https://doi.org/10.3389/fped.2016.00143
  36. Reich, B., Hoeber, D., Bendix, I., & Felderhoff-Mueser, U. (2016). Hyperoxia and the Immature Brain. Developmental Neuroscience, 38(5), 311–330. https://doi.org/10.1159/000454917
  37. Rice, D., & Barone, S. (2000). Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. Environmental Health Perspectives, 108 Suppl 3, 511–533. https://doi.org/10.1289/ehp.00108s3511
  38. Rogan, M. T., Stäubli, U. V., & LeDoux, J. E. (1997). Fear conditioning induces associative long-term potentiation in the amygdala. Nature, 390(6660), 604–607. https://doi.org/10.1038/37601
  39. Saugstad, O. D., Kapadia, V., & Oei, J. L. (2021). Oxygen in the First Minutes of Life in Very Preterm Infants. Neonatology, 118(2), 218–224. https://doi.org/10.1159/000516261
  40. Seibenhener, M. L., & Wooten, M. C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments: JoVE, 96, e52434–e52434. PubMed. https://doi.org/10.3791/52434
  41. Semple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M., & Noble-Haeusslein, L. J. (2013). Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species. Progress in Neurobiology, 106–107, 1–16. https://doi.org/10.1016/j.pneurobio.2013.04.001
  42. Serdar, M., Herz, J., Kempe, K., Lumpe, K., Reinboth, B. S., Sizonenko, S. V., Hou, X., Herrmann, R., Hadamitzky, M., Heumann, R., Hansen, W., Sifringer, M., van de Looij, Y., Felderhoff-Müser, U., & Bendix, I. (2016). Fingolimod protects against neonatal white matter damage and long-term cognitive deficits caused by hyperoxia. Brain, Behavior, and Immunity, 52, 106–119. https://doi.org/10.1016/j.bbi.2015.10.004
  43. Stiles, J., & Jernigan, T. L. (2010). The basics of brain development. Neuropsychology Review, 20(4), 327–348. https://doi.org/10.1007/s11065-010-9148-4
  44. Tucker, A. M., Aquilina, K., Chakkarapani, E., Hobbs, C. E., & Thoresen, M. (2009). Development of Amplitude-Integrated Electroencephalography and Interburst Interval in the Rat. Pediatric Research, 65(1), 62–66. https://doi.org/10.1203/PDR.0b013e3181891316
  45. van Zanten, H. A., Tan, R. N. G. B., Thio, M., de Man-van Ginkel, J. M., van Zwet, E. W., Lopriore, E., & te Pas, A. B. (2014). The risk for hyperoxaemia after apnoea, bradycardia and hypoxaemia in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition, 99(4), F269-273. https://doi.org/10.1136/archdischild-2013-305745
  46. Venerosi, A., Ricceri, L., Scattoni, M. L., & Calamandrei, G. (2009). Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in CD-1 mouse pups. Environmental Health: A Global Access Science Source, 8, 12. https://doi.org/10.1186/1476-069X-8-12
  47. Williams, E., & Scott, J. P. (1954). The development of Social Behavior Patterns in the Mouse, in Relation to Natural Periods 1. https://doi.org/10.1163/156853954X00031
  48. Wiltgen, B. J., Sanders, M. J., Anagnostaras, S. G., Sage, J. R., & Fanselow, M. S. (2006). Context Fear Learning in the Absence of the Hippocampus. Journal of Neuroscience, 26(20), 5484–5491. https://doi.org/10.1523/JNEUROSCI.2685-05.2006
  49. Zafeiriou, D. I. (2004). Primitive reflexes and postural reactions in the neurodevelopmental examination. Pediatric Neurology, 31(1), 1–8. https://doi.org/10.1016/j.pediatrneurol.2004.01.012
  50. Lueptow, L. M. (2017). Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. Journal of Visualized Experiments: JoVE, 126, 55718. https://doi.org/10.3791/55718
  51. Seibenhener, M. L., & Wooten, M. C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments: JoVE, 96, e52434–e52434. PubMed. https://doi.org/10.3791/52434