Glyoxal in hyperglycaemic ischemic stroke – a cohort study

Abstract

Background Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke. Methods In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested. Results Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid Nδ-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids Nε-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal. Conclusions The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke.

The reactive pyruvate metabolite dimethylglyoxal mediates neurological consequences of diabetes

“…However, normalization of high glucose levels with insulin does not improve the outcome of stroke patients with hyperglycemia 2 . These therapeutic deficits challenge the current view, derived from studies looking mostly at peripheral vascular pathology, that hyperglycemia- and glycolysis- (or gluconeogenesis)-dependent reactions drive diabetic CNS complications or the detrimental effects of acute hyperglycemia in stroke 3 – 5 . Instead, we hypothesize that specific features in the development of CNS complications could be due to differences in the energy supply of peripheral and neural cells.…”

Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity

“…There is an increasing number of studies showing the association between neurological disorders and cognitive function and AGEs [46]. Elevated dicarbonyls in plasma and hyperglycemia, are associated with occurrence of cardiovascular incident, including stroke [47], and predicts a worsened outcome in stroke [48]. Moreover, the amount of AGEs in the brain and CSF increases with age, and is more prevalent in people with Alzheimer's disease [49,50] and multiple sclerosis [51].…”

Glyoxal in Foods: Formation, Metabolism, Health Hazards, and Its Control Strategies

“…Glyoxal is a typical α-dicarbonyl compound showing electrophilic activity. 1 People are continuously exposed to glyoxal through diet and the environment, with the former being the main route of exogenous exposure to glyoxal. During food processing, glyoxal can be produced by the Maillard reaction, the autoxidation of D-glucose, the pyrolysis of carbohydrates, and the peroxidation of lipids.…”

“…Glyoxal is a typical α-dicarbonyl compound showing electrophilic activity . People are continuously exposed to glyoxal through diet and the environment, with the former being the main route of exogenous exposure to glyoxal.…”