PMID- 23011809
OWN - NLM
STAT- MEDLINE
DCOM- 20130604
LR  - 20240109
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 47
IP  - 1
DP  - 2013 Feb
TI  - Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the 
      mitochondrial membrane potential in reactive oxygen species generation.
PG  - 9-23
LID - 10.1007/s12035-012-8344-z [doi]
AB  - Stroke and circulatory arrest cause interferences in blood flow to the brain that 
      result in considerable tissue damage. The primary method to reduce or prevent 
      neurologic damage to patients suffering from brain ischemia is prompt restoration 
      of blood flow to the ischemic tissue. However, paradoxically, restoration of 
      blood flow causes additional damage and exacerbates neurocognitive deficits among 
      patients who suffer a brain ischemic event. Mitochondria play a critical role in 
      reperfusion injury by producing excessive reactive oxygen species (ROS) thereby 
      damaging cellular components, and initiating cell death. In this review, we 
      summarize our current understanding of the mechanisms of mitochondrial ROS 
      generation during reperfusion, and specifically, the role the mitochondrial 
      membrane potential plays in the pathology of cerebral ischemia/reperfusion. 
      Additionally, we propose a temporal model of ROS generation in which 
      posttranslational modifications of key oxidative phosphorylation (OxPhos) 
      proteins caused by ischemia induce a hyperactive state upon reintroduction of 
      oxygen. Hyperactive OxPhos generates high mitochondrial membrane potentials, a 
      condition known to generate excessive ROS. Such a state would lead to a "burst" 
      of ROS upon reperfusion, thereby causing structural and functional damage to the 
      mitochondria and inducing cell death signaling that eventually culminate in 
      tissue damage. Finally, we propose that strategies aimed at modulating this 
      maladaptive hyperpolarization of the mitochondrial membrane potential may be a 
      novel therapeutic intervention and present specific studies demonstrating the 
      cytoprotective effect of this treatment modality.
FAU - Sanderson, Thomas H
AU  - Sanderson TH
AD  - Cardiovascular Research Institute, Wayne State University School of Medicine, 
      Detroit, MI 48201, USA. tsanders@med.wayne.edu
FAU - Reynolds, Christian A
AU  - Reynolds CA
FAU - Kumar, Rita
AU  - Kumar R
FAU - Przyklenk, Karin
AU  - Przyklenk K
FAU - Huttemann, Maik
AU  - Huttemann M
LA  - eng
GR  - R01 GM089900/GM/NIGMS NIH HHS/United States
GR  - R01 NS076715/NS/NINDS NIH HHS/United States
GR  - GM089900/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120926
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*metabolism/*pathology
MH  - Cytoprotection
MH  - Humans
MH  - *Membrane Potential, Mitochondrial
MH  - Models, Biological
MH  - Reactive Oxygen Species/*metabolism
MH  - Reperfusion Injury/*metabolism/*pathology
PMC - PMC3725766
MID - NIHMS450957
EDAT- 2012/09/27 06:00
MHDA- 2013/06/05 06:00
PMCR- 2014/02/01
CRDT- 2012/09/27 06:00
PHST- 2012/04/30 00:00 [received]
PHST- 2012/08/27 00:00 [accepted]
PHST- 2012/09/27 06:00 [entrez]
PHST- 2012/09/27 06:00 [pubmed]
PHST- 2013/06/05 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - 10.1007/s12035-012-8344-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2013 Feb;47(1):9-23. doi: 10.1007/s12035-012-8344-z. Epub 2012 Sep 
      26.