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Review
. 2014 Jun;45(6):1881-6.
doi: 10.1161/STROKEAHA.114.004889. Epub 2014 Apr 17.

Opposing effects of glucose on stroke and reperfusion injury: acidosis, oxidative stress, and energy metabolism

Nathaniel M Robbins  1 , Raymond A Swanson  2
Affiliations
Review

Opposing effects of glucose on stroke and reperfusion injury: acidosis, oxidative stress, and energy metabolism

Nathaniel M Robbins et al. Stroke. 2014 Jun.
No abstract available

Keywords: acidosis; hemorrhage; hyperglycemia; hypoglycemia; reactive oxygen species; superoxides.

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Figures

Figure 1
Figure 1
Metabolic fates of glucose relevant to ischemic injury. Products thought to have favorable effects on stroke outcome are shown in blue font, and products thought to have deleterious effects are in red font. Glucose metabolized by the hexose monophosphate provides reducing equivalents for producing NADPH. NADPH in turn can be used by glutathione reductase (GR) to regenerate glutathione (GSH) from glutathione disulfide (GSSG), and for the production of nitric oxide (NO·) by nitric oxide synthase or superoxide (O2·) by NADPH oxidase (NOX). ATP is produced by glycolytic production of glucose to pyruvate and NADH. Pyruvate and NADH are normally oxidized to CO2 and NAD+ by mitochondrial respiration to generate additional ATP. Under ischemic conditions, oxidative metabolism cannot occur and NAD+ is instead regenerated by the formation of lactic acid. During reperfusion, damaged mitochondria may produce superoxide by donating glucose-derived reducing equivalents to molecular oxygen.
Figure 2
Figure 2
Differing effects of hyperglycemia on ischemic core, penumbra, and reperfusion. Complete or near-complete ischemia in core regions with poor collateral circulation leads to glucose and oxygen depletion, accompanied by ATP depletion and mild acidosis. Hyperglycemia supports metabolism and exacerbates the acidosis to only a minor degree in core regions, because only the glucose present at onset of ischemia is metabolized. Penumbral regions with residual blood flow through collateral circulation receive continued glucose but not oxygen delivery, due to the molar excess of glucose in arterial blood. Glycolysis fueled by the continued glucose delivery can attenuate ATP depletion, but also generates lactic acidosis in proportion to blood glucose levels. During reperfusion pH is normalized and ATP recovers where tissue is still viable, but with increased glucose delivery there is increased production of reactive oxygen species.
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