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Growing evidence indicates that astrocytes, key metabolic regulators of the neurovascular unit, modulate neuronal susceptibility to genomic injury through redox buffering, NAD+ maintenance, and metabolic support. In the metabolically impaired yet structurally preserved penumbra, astrocytic control of glutathione turnover, mitochondrial function, and lactate shuttling may determine whether oxidative DNA lesions are efficiently repaired or progress toward energetic collapse. Poly(ADP-ribose) polymerase 1 activation following DNA strand breaks couples genomic stress to NAD+ depletion and bioenergetic failure, forming a critical interface between redox biology and metabolism. This framework posits that astrocytes preserve genomic integrity not by directly altering DNA repair pathways but by sustaining the energetic capacity required for an effective DNA damage response. Elucidating this astrocyte-centered redox\u2013metabolic axis may reveal therapeutic strategies to stabilize penumbral tissue and improve stroke outcomes.<\/jats:p>","DOI":"10.3390\/cells15121103","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:33:54Z","timestamp":1781768034000},"page":"1103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7277-721X","authenticated-orcid":false,"given":"Renata","family":"Ko\u0142odziejska","sequence":"first","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0406-8421","authenticated-orcid":false,"given":"Antoni","family":"Godlewski","sequence":"additional","affiliation":[{"name":"Student Scientific Club of Biochemistry and Bioorganic Chemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2015-7510","authenticated-orcid":false,"given":"Agnieszka","family":"Tafelska-Kaczmarek","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemistry, Nicolaus Copernicus University in Toru\u0144, Gagarina 7, 87-100 Toru\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kuk","sequence":"additional","affiliation":[{"name":"Student Scientific Club of Biochemistry and Bioorganic Chemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Moritz","sequence":"additional","affiliation":[{"name":"Student Scientific Club of Biochemistry and Bioorganic Chemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5415-6050","authenticated-orcid":false,"given":"Krzysztof","family":"Sergot","sequence":"additional","affiliation":[{"name":"Institute of Applied Radiation Chemistry, Laboratory of Laser Molecular Spectroscopy, Faculty of Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-1092","authenticated-orcid":false,"given":"Natalia","family":"Kurhaluk","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, Institute of Biology, Pomeranian University in S\u0142upsk, Arciszewskiego 22a, 76-200 S\u0142upsk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-9005","authenticated-orcid":false,"given":"Halina","family":"Tkaczenko","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, Institute of Biology, Pomeranian University in S\u0142upsk, Arciszewskiego 22a, 76-200 S\u0142upsk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-4796","authenticated-orcid":false,"given":"Alina","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrneurol.2012.98","article-title":"The Immunology of Acute Stroke","volume":"8","author":"Chamorro","year":"2012","journal-title":"Nat. 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