ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Transcriptomic identification of CREB1 and FOXO1 activation in neuregulin-1–mediated neuroprotection after stroke
Kimberly Bennett 1
Monique C Surles-Zeigler 2
Catherine Augello 3
Etchi Ako 3
Hakeem Omotayo 3
Gregory Ford 2
Victor G J Rodgers 3
Byron Ford 2
1. Harvard-MIT Program in Health Sciences and Technology, Cambridge, United States
2. Howard University, Washington, D.C., United States
3. University of California Riverside Marlan and Rosemary Bourns College of Engineering, Riverside, United States
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Abstract
Background: Neuregulin-1 (NRG-1) is a growth factor that has been investigated for its neuroprotective properties following ischemic stroke. While NRG-1 has shown considerable promise in reducing neuronal damage, the molecular mechanisms underlying its protective effects remain unclear. This study aimed to examine the impact of NRG-1 treatment on ischemia-induced gene expression following permanent middle cerebral artery occlusion (MCAO) in rats. Methods: Rats were treated with either NRG-1 or vehicle then sacrificed 3 and 12 hours after permanent MCAO. RNA isolated from the peri-infarct cortex (ischemic penumbra) was hybridized to an Affymetrix Rat Genome 2.0 ST Microarray Gene Chip. Gene expression was analyzed using the Affymetrix Transcriptome Analysis Console (TAC) 4.0 software and the STRING Protein–Protein Interaction Networks database. Results: NRG-1 treatment upregulated transcriptional programs promoting cell survival and anti-inflammatory signaling. CREB1 and FOXO1 transcription factor pathways, which are associated with anti-inflammatory signaling, cell proliferation, reduced apoptosis, and decreased oxidative stress, were upregulated. Consistent with the transcriptomic findings, Luminex multiplex transcription factor assays validated the increased CREB1 and FOXO1 activity in NRG-1–treated MCAO brains. Conclusion: These findings provide novel insight into the molecular mechanisms by which NRG-1 mediates neuroprotection, highlighting its role in activating transcriptional programs that promote neuronal survival and resilience following ischemic injury.
Summary
Keywords
bioinformatics, ischemic stroke, neuregulin, Neuroprotection, transcription factor, Transcriptomics
Received
06 November 2025
Accepted
12 February 2026
Copyright
© 2026 Bennett, Surles-Zeigler, Augello, Ako, Omotayo, Ford, Rodgers and Ford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Byron Ford
Disclaimer
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