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
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/5/15
Y1 - 2018/5/15
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. This article is part of the Special Issue entitled ‘Cerebral Ischemia’.
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. This article is part of the Special Issue entitled ‘Cerebral Ischemia’.
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
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U2 - 10.1016/j.neuropharm.2017.11.011
DO - 10.1016/j.neuropharm.2017.11.011
M3 - Review article
C2 - 29128308
AN - SCOPUS:85033802078
SN - 0028-3908
VL - 134
SP - 208
EP - 217
JO - Neuropharmacology
JF - Neuropharmacology
ER -