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Peeples ES, Sahar NE, Snyder W, et al. Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury. Pediatr Res. 2021;doi: 10.1038/s41390-021-01701-5.
Peeples, E. S., Sahar, N. E., Snyder, W., & Mirnics, K. (2021). Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury. Pediatric research, . https://doi.org/10.1038/s41390-021-01701-5
Peeples, Eric S, et al. "Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury." Pediatric research vol. (2021). doi: https://doi.org/10.1038/s41390-021-01701-5
Peeples ES, Sahar NE, Snyder W, Mirnics K. Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury. Pediatr Res. 2021 Aug 31; doi: 10.1038/s41390-021-01701-5. Epub 2021 Aug 31. PMID: 34465878.
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Pediatr Res. 2021 Aug 31; doi: 10.1038/s41390-021-01701-5. Epub 2021 Aug 31.

Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury.

Pediatric research

Eric S Peeples, Namood-E Sahar, William Snyder, Karoly Mirnics

Affiliations

  1. Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA. [email protected].
  2. Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
  3. Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
  4. Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
  5. Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA.

PMID: 34465878 DOI: 10.1038/s41390-021-01701-5

Abstract

BACKGROUND: Neonatal hypoxic-ischemic brain injury (HIBI) results in significant morbidity and mortality despite current standard therapies. MicroRNAs (miRNAs) are a promising therapeutic target; however, there is a paucity of data on endogenous miRNA expression of the brain after HIBI during the primary therapeutic window (6-72 h after injury).

METHODS: Postnatal day 9 mouse pups underwent unilateral carotid ligation+hypoxia (HIBI), sham surgery+hypoxia, or sham surgery+normoxia (controls). miRNA sequencing was performed on the ipsilateral brain of each of the three groups plus the contralateral HIBI brain at 24 and 72 h after injury. Findings were validated in eight key miRNAs by quantitative polymerase chain reaction.

RESULTS: Hypoxia resulted in significant differential expression of 38 miRNAs at both time points. Mir-2137, -335, -137, and -376c were significantly altered by neonatal HIBI at 24 and 72 h, with 3 of the 4 demonstrating multiphasic expression (different direction of differential expression at 24 versus 72 h).

CONCLUSIONS: Our global assessment of subacute changes in brain miRNA expression after hypoxia or HIBI will advance research into targeted miRNA-based interventions. It will be important to consider the multiphasic miRNA expression patterns after HIBI to identify optimal timing for individual interventions.

IMPACT: This study is the first to comprehensively define endogenous brain microRNA expression changes outside of the first hours after neonatal hypoxic-ischemic brain injury (HIBI). Mir-2137, -335, -137, and -376c were significantly altered by neonatal HIBI and therefore deserve further investigation as possible therapeutic targets. The expression profiles described will support the design of future studies attempting to develop miRNA-based interventions for infants with HIBI. At 24 h after injury, contralateral HIBI miRNA expression patterns were more similar to ipsilateral HIBI than to controls, suggesting that the contralateral brain is not an appropriate "internal control" for miRNA studies in this model.

© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

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