The effect of post‐stroke hyperglycaemia on the levels of brain damage and repair‐related circulating biomarkers: the Glycaemia in Acute Stroke Study II

Abstract

Background and purpose The aim was to identify whether post‐stroke hyperglycaemia (PSH) influences the levels of circulating biomarkers of brain damage and repair, and to explore whether these biomarkers mediate the effect of PSH on the ischaemic stroke (IS) outcome. Methods This was a secondary analysis of the Glycaemia in Acute Stroke II study. Biomarkers of inflammation, prothrombotic activity, endothelial dysfunction, blood–brain barrier rupture, cell death and brain repair processes were analysed at 24–48 h (baseline) and 72–96 h (follow‐up) after IS. The associations of the biomarkers and stroke outcome (modified Rankin Scale score at 3 months) based on the presence of PSH were compared. Results A total of 174 patients participated in this sub‐study. Brain‐derived neurotrophic factor (BDNF) at admission was negatively correlated with glucose levels. PSH was associated with a trend toward higher levels of endothelial progenitor cells (EPCs) at baseline. The EPCs in the PSH group then decreased in the follow‐up samples (−8.5 ± 10.3) compared with the non‐PSH group (4.7 ± 7.33; P = 0.024). However, neither BDNF nor EPC values had correlation with the 3‐month outcome. Higher interleukin‐6 at follow‐up was associated with poor outcomes (modified Rankin Scale > 2) independently of PSH. Conclusion Post‐stroke hyperglycaemia appears to be associated with a negative regulation of BDNF and a different reaction in EPC levels. However, neither BDNF nor EPCs showed significant mediation of the PSH association with IS outcome, and only higher interleukin‐6 in the follow‐up samples (72–96 h) was related to poor outcomes, independently of PSH status. Further studies are needed to achieve definite conclusions.

Effects of β-Adrenergic Blockade on Metabolic and Inflammatory Responses in a Rat Model of Ischemic Stroke

“…Tight glycemic control in the management of acute ischemic stroke remains controversial due to the hypoglycemic consequences [32]. Despite the debate, the control of stress hyperglycemia and having it return to the normal range is of benefit to ischemic stroke subjects, as seen in experimental studies [4,33,34]. The homeostatic regulation of circulating glucose levels is strictly counterbalanced by gluconeogenesis, glycogenolysis, and glucose uptake as it occurred in the liver, adipose tissues, skeletal muscles, and kidney.…”

“…Additionally, the increased risk of intracerebral hemorrhagic transformation and its accompanied inflammation further exhaust the beneficial effects of tPA. Clinical findings indicate that hyperglycemia is critical in counterbalancing the therapeutic benefits and increasing the adverse complications of tPA through an action mode related to inflammation exacerbation [2][3][4][5]. Despite their protective and regenerative potential, overwhelming hyperglycemia and neuroinflammation have been implicated in the pathogenesis of stroke.…”

Ultrastructural studies of the neurovascular unit reveal enhanced endothelial transcytosis in hyperglycemia‐enhanced hemorrhagic transformation after stroke

“…In the sham control group, we observed intact and homogeneous NVU ultrastructure typical for the homeostatic brain, 19,38,39 characterized by the homogenous intercellular tight junction structures between BMECs, few endothelial vesicles inside BMECs, and surrounding pericytes and astrocyte end‐feet with normal morphology (Figure 2A). The numbers of endothelial vesicles were increased markedly 4 h after MCAO in NG mice (Figure 2B), and were further elevated in the HG group (Figure 2C), whereas no prominent abnormalities were found in the ultrastructure of tight junctions at this time point.…”

<p>Metabolic Syndrome Predicts Poor Outcome in Acute Ischemic Stroke Patients After Endovascular Thrombectomy</p>

“…It can cause intracellular acidosis and mitochondrial dysfunction and enhance the generation of reactive oxygen species and extracellular glutamate, which might induce the exaggeration of neuronal damage and disruption of blood-brain barrier. [28][29][30] These results highlighted the need for further randomized controlled trials to determine whether the modulation of blood glucose within an appropriate range could improve functional outcomes in ischemic stroke treated with EVT.…”