Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six Month Post-Exposure Analysis

Vikram Subramanian; Denise Juhr; Piero Giansanti; Isabella M. Grumbach

doi:10.1021/acsomega.5c09726

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Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six Month Post-Exposure Analysis

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Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six Month Post-Exposure Analysis

Vikram Subramanian, Denise Juhr, Piero Giansanti and Isabella M. Grumbach

ACS omega, Vol.10(43), pp.52046-52059

10/26/2025

DOI: 10.1021/acsomega.5c09726

PMCID: PMC12593089

PMID: 41210773

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Abstract

Radiation therapy (RT) treats primary and metastatic brain tumors, with about one million Americans surviving beyond six months post-treatment. However, up to 90% of these survivors develop RT-induced cognitive impairment. Emerging evidence links cognitive decline to RT-induced endothelial dysfunction in brain microvessels, yet in vivo studies remain limited. Investigating the molecular and cellular pathways connecting RT, endothelial injury, and cognitive impairment is vital for developing targeted interventions. We performed quantitative proteomic analysis of cerebral microvessels from five control and five irradiated mice (12 Gy) 6 months post-RT. Bioinformatics tools, including gene ontology (GO) enrichment, Mitocarta analysis, Ingenuity Pathway Analysis (IPA), and iPathwayGuide, identified affected pathways. Findings were validated by Western blotting. RT significantly altered 414 proteins, with 157 upregulated and 257 downregulated. GO analysis indicated metabolic pathway disruptions, and Mitocarta analysis revealed a significant presence of mitochondrial proteins among the dysregulated proteins. IPA identified 76 enriched canonical pathways, 34 transcription regulators, 6 nuclear receptors, and 5 growth factors involved in RT-induced damage responses. IPA predicted mitochondrial dysfunction in the irradiated group, confirmed by Western blotting. Significant proteomic changes in cerebral microvessels suggest RT-induced metabolic dysfunction in cerebral microvasculature, including oxidative phosphorylation, the TCA cycle, and glycolysis.

Details

Title: Subtitle: Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six Month Post-Exposure Analysis
Creators: Vikram Subramanian - University of Iowa
Denise Juhr - University of Iowa, Internal Medicine
Piero Giansanti - TUM Klinikum
Isabella M. Grumbach - University of Iowa
Resource Type: Journal article
Publication Details: ACS omega, Vol.10(43), pp.52046-52059
DOI: 10.1021/acsomega.5c09726
PMID: 41210773
PMCID: PMC12593089
NLM abbreviation: ACS Omega
ISSN: 2470-1343
eISSN: 2470-1343
Publisher: American Chemical Society
Grant note: University of Iowa: NA Deutsche Forschungsgemeinschaft: INST 95/1650-1 National Institutes of Health: R01 EY031544 U.S. Department of Veterans Affairs: I01 BX000163
We would like to acknowledge the Genomics Division of the Iowa Institute of Human Genetics for their assistance in the preparation of proteomics samples. Some data presented herein were obtained at the Bioinformatics Division of the Iowa Institute of Human Genetics.
Language: English
Date published: 10/26/2025
Academic Unit: Cardiovascular Medicine; Urology; Internal Medicine
Record Identifier: 9985019042602771

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