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 -