A review of stress-induced hyperglycaemia in the context of acute ischaemic stroke: Definition, underlying mechanisms, and the status of insulin therapy.

The transient elevation of blood glucose produced following acute ischaemic stroke (AIS) has been described as stress-induced hyperglycaemia (SIH). SIH is common even in patients with AIS who have no previous diagnosis of diabetes mellitus. Elevated blood glucose levels during admission and hospitalization are strongly associated with enlarged infarct size and adverse prognosis in AIS patients. However, insulin-intensive glucose control therapy defined by admission blood glucose for SIH has not achieved the desired results, and new treatment ideas are urgently required. First, we explore the various definitions of SIH in the context of AIS and their predictive value in adverse outcomes. Then, we briefly discuss the mechanisms by which SIH arises, describing the dual effects of elevated glucose levels on the central nervous system. Finally, although preclinical studies support lowering blood glucose levels using insulin, the clinical outcomes of intensive glucose control are not promising. We discuss the reasons for this phenomenon.

Neutrophil Heterogeneity and its Roles in the Inflammatory Network after Ischemic Stroke.

As the first peripheral immune cells to enter the brain after ischemic stroke, neutrophils are important participants in stroke-related neuroinflammation. Neutrophils are quickly mobilized from the periphery in response to a stroke episode and cross the blood-brain barrier to reach the ischemic brain parenchyma. This process involves the mobilization and activation of neutrophils from peripheral immune organs (including the bone marrow and spleen), their chemotaxis in the peripheral blood, and their infiltration into the brain parenchyma (including disruption of the blood-brain barrier, inflammatory effects on brain tissue, and interactions with other immune cell types). In the past, it was believed that neutrophils aggravated brain injuries through the massive release of proteases, reactive oxygen species, pro-inflammatory factors, and extracellular structures known as neutrophil extracellular traps (NETs). With the failure of early clinical trials targeting neutrophils and uncovering their underlying heterogeneity, our view of their role in ischemic stroke has become more complex and multifaceted. As neutrophils can be divided into N1 and N2 phenotypes in tumors, neutrophils have also been found to have similar phenotypes after ischemic stroke, and play different roles in the development and prognosis of ischemic stroke. N1 neutrophils are dominant during the acute phase of stroke (within three days) and are responsible for the damage to neural structures via the aforementioned mechanisms. However, the proportion of N2 neutrophils gradually increases in later phases, and this has a beneficial effect through the release of anti-inflammatory factors and other neuroprotective mediators. Moreover, the N1 and N2 phenotypes are highly plastic and can be transformed into each other under certain conditions. The pronounced differences in their function and their high degree of plasticity make these neutrophil subpopulations promising targets for the treatment of ischemic stroke.