Stress hyperglycemia exacerbates inflammatory brain injury after stroke

Area of Science:

• Neuroscience
• Metabolic disorders
• Ischemic stroke research

Background:

• Hyperglycemia is a common stress response in ischemic stroke patients, but its impact on stroke outcomes remains unclear.
• Existing clinical and preclinical data do not definitively link post-stroke hyperglycemia to functional outcomes.
• Investigating the role of hyperglycemia in stroke recovery is crucial for developing targeted therapeutic strategies.

Approach:

• Utilized a mouse model of permanent ischemic stroke.
• Maintained mice under normoglycemic or hyperglycemic conditions between 17 and 48 hours post-ischemia.
• Assessed infarct volume, blood-brain barrier integrity, hemorrhage, motor function, and oxidative stress markers (superoxide formation).
• Examined the role of NADPH oxidase-2 in mediating hyperglycemic effects using p47^phox-/- mice.

Key Points:

• Post-stroke hyperglycemia significantly increased infarct volume, blood-brain barrier disruption, and hemorrhage in mice.
• Hyperglycemia led to impaired motor recovery in the ischemic stroke model.
• Elevated blood sugar increased superoxide formation by peri-infarct microglia/macrophages, indicating heightened oxidative stress.
• These detrimental effects were abolished in p47^phox-/- mice, implicating NADPH oxidase-2 in the mechanism.

Conclusions:

• Hyperglycemia occurring hours to days after ischemic stroke exacerbates brain damage and functional deficits.
• Oxidative stress, mediated by NADPH oxidase activity in microglia/macrophages, is a key mechanism linking post-stroke hyperglycemia to poor outcomes.
• Targeting hyperglycemia and associated oxidative stress pathways may offer a therapeutic approach to improve stroke recovery.