Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke

Area of Science:

• Neuroscience
• Cardiovascular Science
• Metabolic Disorders

Background:

• Obesity is a known risk factor for stroke.
• Obesity is linked to worse outcomes following a stroke.
• The mechanisms behind poorer stroke outcomes in obesity are not fully understood.

Purpose of the Study:

• To investigate the role of brain microvascular disruption in poorer stroke outcomes associated with obesity.
• To compare microvascular changes in obese versus lean mice after experimental stroke.

Main Methods:

• Focal cerebral ischemia was induced in obese (ob/ob) and lean mice using transient middle cerebral artery occlusion.
• Assessed incidence of hemorrhagic transformation and ischemic brain damage volume.
• Measured blood-brain barrier permeability and brain microvascular matrix metalloproteinase-9 (MMP-9) expression.

Main Results:

• Obese mice showed a significantly greater incidence of hemorrhagic transformation and larger ischemic brain damage volumes compared to lean mice.
• Blood-brain barrier permeability was markedly increased in obese mice.
• Brain microvascular MMP-9 expression was also significantly elevated in obese mice.

Conclusions:

• Obesity potentiates brain microvascular disruption following experimental stroke.
• These microvascular changes, including increased blood-brain barrier permeability and MMP-9 expression, contribute to poorer stroke outcomes in obesity.
• The observed effects were independent of leptin or glycemic status, highlighting obesity itself as a key factor.