Neuro-oxidative-nitrosative stress in sepsis
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Neuro-oxidative-nitrosative stress in sepsis. / Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 31, No. 7, 07.2011, p. 1532-44.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Neuro-oxidative-nitrosative stress in sepsis
AU - Berg, Ronan M G
AU - Møller, Kirsten
AU - Bailey, Damian M
PY - 2011/7
Y1 - 2011/7
N2 - Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding brain parenchyma, due to failure of the local antioxidant systems. ROS/RNS cause structural membrane damage, induce inflammation, and scavenge nitric oxide (NO) to yield peroxynitrite (ONOO(-)). This activates the inducible NO synthase, which further compounds ONOO(-) formation. ROS/RNS cause mitochondrial dysfunction by inhibiting the mitochondrial electron transport chain and uncoupling oxidative phosphorylation, which ultimately leads to neuronal bioenergetic failure. Furthermore, in certain 'at risk' areas of the brain, free radicals may induce neuronal apoptosis. In the present review, we define a role for ROS/RNS-mediated neuronal bioenergetic failure and apoptosis as a primary mechanism underlying sepsis-associated encephalopathy and, in sepsis survivors, permanent cognitive deficits.
AB - Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding brain parenchyma, due to failure of the local antioxidant systems. ROS/RNS cause structural membrane damage, induce inflammation, and scavenge nitric oxide (NO) to yield peroxynitrite (ONOO(-)). This activates the inducible NO synthase, which further compounds ONOO(-) formation. ROS/RNS cause mitochondrial dysfunction by inhibiting the mitochondrial electron transport chain and uncoupling oxidative phosphorylation, which ultimately leads to neuronal bioenergetic failure. Furthermore, in certain 'at risk' areas of the brain, free radicals may induce neuronal apoptosis. In the present review, we define a role for ROS/RNS-mediated neuronal bioenergetic failure and apoptosis as a primary mechanism underlying sepsis-associated encephalopathy and, in sepsis survivors, permanent cognitive deficits.
KW - Animals
KW - Apoptosis
KW - Brain/metabolism
KW - Brain Diseases, Metabolic/etiology
KW - Cognition
KW - Humans
KW - Reactive Nitrogen Species/metabolism
KW - Reactive Oxygen Species/metabolism
KW - Sepsis/complications
U2 - 10.1038/jcbfm.2011.48
DO - 10.1038/jcbfm.2011.48
M3 - Review
C2 - 21487413
VL - 31
SP - 1532
EP - 1544
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 7
ER -
ID: 236993910