Neutrophil extracellular traps increased by hyperglycemia exacerbate ischemic brain damage.

• More NETs were found in thrombus from patients suffering from stroke associated with hyperglycemia. • Hyperglycemia primes NETosis in peri-infarction brain tissue of pMCAO mice. • Neutrophil extracellular traps exacerbate ischemic brain damage in pMCAO mice. • Inhibition of NETosis could partly eliminate the harmful effect of hyperglycemia on ischemic brain injury. Hyperglycemia is common and associated with poor outcome in acute ischemic stroke patients. Neutrophil extracellular traps (NETs) are increased either in diabetes or ischemic stroke. We aimed to determine the role of NETs in acute ischemic stroke with hyperglycemia as it has not been clarified. NETs were observed in thrombi retrieved from ischemic stroke patients undergoing endovascular treatment. Citrullinated histone H3 was much more abundant in thrombi from hyperglycemic patients than in those from normoglycemic patients. BKS-db/db and wild-type mice injected with glucose were used to establish the permanent middle cerebral artery occlusion model with hyperglycemia. NETs induced by hyperglycemia were detected in the peri-ischemic brain tissue. Inhibition of NET formation decreased the infarction volume both in db/db and wild-type mice with hyperglycemia. Neurological function deficits were alleviated by blocking NET formation. These findings suggest that NETs increased by hyperglycemia play a role in exacerbation of ischemic brain damage. [ABSTRACT FROM AUTHOR]