Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery

Peiying Li, R. Anne Stetler, Rehana K. Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V.L. Bennett, Jun Chen

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ). Defective DNA repair is tightly correlated with worse neurological outcomes after stroke, whereas upregulation of DNA repair enzymes, such as APE1, OGG1, and XRCC1, improves long-term functional recovery following stroke. Indeed, DNA damage and repair are now known to play critical roles in fundamental aspects of stroke recovery, such as neurogenesis, white matter recovery, and neurovascular unit remodeling. Several DNA repair enzymes are essential for comprehensive neural repair mechanisms after stroke, including Polβ and NEIL3 for neurogenesis, APE1 for white matter repair, Gadd45b for axonal regeneration, and DNA-PKs for neurovascular remodeling. This review discusses the emerging role of DNA damage and repair in functional recovery after stroke and highlights the contribution of DNA repair to regenerative elements after stroke. This article is part of the Special Issue entitled ‘Cerebral Ischemia’.

Original languageEnglish (US)
Pages (from-to)208-217
Number of pages10
JournalNeuropharmacology
Volume134
DOIs
StatePublished - May 15 2018

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Keywords

  • Axonal regeneration
  • Cerebral ischemia
  • DNA damage
  • DNA repair
  • Neurogenesis
  • Neurovascular remodeling
  • Oxidative stress
  • Stroke recovery
  • White matter repair

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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