Timing-Dependent Effects of Dexamethasone in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury: A Transcriptomic Analysis of Synaptic Signaling and Calcium Homeostasis.

Overview

Authors: Joohee Lim¹, Jungho Han¹, Jeung Eun Shin¹, Kwangsoo Jung², Il-Sun Kim¹, Younhee Ko³, Kook In Park¹

ORCID iDs: Joohee Lim, Jungho Han, Jeung Eun Shin, Kwangsoo Jung, Younhee Ko

Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (J.L.); (J.H.); (J.E.S.); (I.-S.K.)
Research and Development Team, Radexel Inc. Seoul 04387, Republic of Korea
Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 17035, Republic of Korea

Institutions: Yonsei University (South Korea); Yonsei University Health System (South Korea); Hankuk University of Foreign Studies (South Korea)

Journal: International journal of molecular sciences, volume 27, issue 11, article 4920

Dates: received 28 April 2026; accepted 27 May 2026; published online 29 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.3390/ijms27114920 · PMID 42278447 · PMCID PMC13256103 · OpenAlex W7163150625

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population), stroke (population)

Methods: Statistics, Graphs

Keywords: neonatal hypoxic–ischemic brain injury, dexamethasone, neuroprotection, transcriptomics, synaptic signaling, calcium homeostasis

MeSH: Calcium*, Dexamethasone*, Hypoxia-Ischemia, Brain*, Neuroprotective Agents*, Synapses*, Transcriptome*, Animals, Animals, Newborn, Disease Models, Animal, Gene Expression Profiling, Homeostasis, Male, Mice, Mice, Inbred C57BL (* major topic)

Topic: Neonatal and fetal brain pathology (Pediatrics, Perinatology and Child Health, Medicine), according to OpenAlex

Citations: not cited yet (Europe PMC); 41 references in the paper

Abstract

The optimal timing and therapeutic role of dexamethasone for neuroprotection in neonatal hypoxic–ischemic (HI) brain injury remain unclear. We investigated whether dexamethasone-mediated neuroprotection is time-dependent and explored its underlying molecular mechanisms in a neonatal HI mouse model. The Rice–Vannucci model (unilateral carotid artery ligation followed by 8% O2 for 90 min) was constructed utilizing postnatal day 7 mice who received vehicle (n = 5), dexamethasone pre-treatment (0.5 mg/kg, 6 h before HI; n = 6), or dexamethasone post-treatment (0.5 mg/kg, 6 h after HI; n = 6). Brain injury severity was evaluated by two blinded investigators 72 h after HI, who measured the whitish discoloration in the ipsilateral hemisphere. Transcriptomic analysis was performed using five representative brain samples from each group. Dexamethasone pre-treatment significantly reduced the area of whitish discoloration compared with the vehicle (p < 0.001); dexamethasone post-treatment exerted no significant protective effect. Transcriptomic profiling identified 962 (407 upregulated and 555 downregulated) differentially expressed genes. Genes with upregulated expressions were enriched in pathways related to central nervous system development, synaptic signaling, and calcium homeostasis; those with downregulated expressions were associated with cellular metabolic processes. Protein–protein interaction network analysis identified Dlg4, Calm1, and Grin1 as hub genes. qRT-PCR validation confirmed significant upregulation of Grin1 and Calm1, whereas Dlg4 showed a concordant but non-significant trend. These findings suggest that dexamethasone pre-treatment may be associated with time-dependent changes in synaptic- and calcium-related gene expression following neonatal HI injury, providing insight into the optimal therapeutic window for neonatal HI brain injury.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

geo:GSE325742, at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

The data discussed in this publication have been deposited in NCBI’s Gene Expression Omnibus [42] and are accessible through GEO Series accession number GSE325742 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325742, accessed on 26 May 2026).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 6 keywords, 14 MeSH terms, 41 references.

Cite

This paper

Lim, J., Han, J., Shin, J. E., Jung, K., Kim, I.-S., Ko, Y., & Park, K. I. (2026). Timing-Dependent Effects of Dexamethasone in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury: A Transcriptomic Analysis of Synaptic Signaling and Calcium Homeostasis. International journal of molecular sciences, 27(11), 4920. https://doi.org/10.3390/ijms27114920

BibTeX

@article{lim2026timing, author = {Lim, Joohee and Han, Jungho and Shin, Jeung Eun and Jung, Kwangsoo and Kim, Il-Sun and Ko, Younhee and Park, Kook In}, title = {{Timing-Dependent Effects of Dexamethasone in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury: A Transcriptomic Analysis of Synaptic Signaling and Calcium Homeostasis}}, journal = {International journal of molecular sciences}, year = {2026}, month = may, volume = {27}, number = {11}, pages = {4920}, publisher = {Multidisciplinary Digital Publishing Institute (MDPI)}, issn = {1422-0067}, doi = {10.3390/ijms27114920}, url = {https://doi.org/10.3390/ijms27114920}, pmid = {42278447}, pmcid = {PMC13256103} }

RIS

TY - JOUR AU - Lim, Joohee AU - Han, Jungho AU - Shin, Jeung Eun AU - Jung, Kwangsoo AU - Kim, Il-Sun AU - Ko, Younhee AU - Park, Kook In TI - Timing-Dependent Effects of Dexamethasone in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury: A Transcriptomic Analysis of Synaptic Signaling and Calcium Homeostasis T2 - International journal of molecular sciences J2 - Int J Mol Sci PY - 2026 DA - 2026/05/29 VL - 27 IS - 11 SP - 4920 SN - 1422-0067 PB - Multidisciplinary Digital Publishing Institute (MDPI) DO - 10.3390/ijms27114920 UR - https://doi.org/10.3390/ijms27114920 LA - en ER -

CSL-JSON

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