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 journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
JournalNeuropharmacology
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Brain Ischemia
DNA Repair
DNA Damage
Oxidative Stress
Stroke
Genome
DNA Repair Enzymes
Neurogenesis
Therapeutics
DNA
Neuroglia
Brain Injuries
Blood Vessels
Regeneration
Cell Death
Up-Regulation
Neurons
Research

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

Cite this

Oxidative stress and DNA damage after cerebral ischemia : Potential therapeutic targets to repair the genome and improve stroke recovery. / Li, Peiying; Stetler, R. Anne; Leak, Rehana K.; Shi, Yejie; Li, Yan; Yu, Weifeng; Bennett, Michael V. L.; Chen, Jun.

In: Neuropharmacology, 01.01.2017.

Research output: Contribution to journalArticle

@article{c7fd4dacd9a4427e8ec94320f5d265bb,
title = "Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery",
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.",
keywords = "Axonal regeneration, Cerebral ischemia, DNA damage, DNA repair, Neurogenesis, Neurovascular remodeling, Oxidative stress, Stroke recovery, White matter repair",
author = "Peiying Li and Stetler, {R. Anne} and Leak, {Rehana K.} and Yejie Shi and Yan Li and Weifeng Yu and Bennett, {Michael V. L.} and Jun Chen",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.neuropharm.2017.11.011",
language = "English (US)",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Oxidative stress and DNA damage after cerebral ischemia

T2 - Potential therapeutic targets to repair the genome and improve stroke recovery

AU - Li, Peiying

AU - Stetler, R. Anne

AU - Leak, Rehana K.

AU - Shi, Yejie

AU - Li, Yan

AU - Yu, Weifeng

AU - Bennett, Michael V. L.

AU - Chen, Jun

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Axonal regeneration

KW - Cerebral ischemia

KW - DNA damage

KW - DNA repair

KW - Neurogenesis

KW - Neurovascular remodeling

KW - Oxidative stress

KW - Stroke recovery

KW - White matter repair

UR - http://www.scopus.com/inward/record.url?scp=85033802078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033802078&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2017.11.011

DO - 10.1016/j.neuropharm.2017.11.011

M3 - Article

C2 - 29128308

AN - SCOPUS:85033802078

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -