Background:
Stroke is a leading cause of serious long-term adult disability in the United States. Hyperglycemia has consistently been associated with worse clinical outcomes from ischemic stroke. Animal studies utilizing genetic models of type II diabetes have shown greater ischemic injury in the setting of hyperglycemia. However, these models may not well represent all physiological aspects of human type II diabetes and post-stroke hyperglycemia. Diet induced diabetes may prove more analogous to human disease. The high fat diet mouse model of type II diabetes reliably creates a subacute hyperglycemic state. We evaluated normal and high fat diet (HFD) fed mice following middle cerebral artery occlusion (MCAO) to determine if post-ischemic functional status is influenced by hyperglycemia in this model.
Methods:
C57BL/6 male mice (12-18 weeks) fed either normal diet or HFD (60%kCal fat) were subjected to 60 minutes of transient MCAO via 6-0 monofilament. Triphenyltetrazolium chloride staining confirmed infarction in a subset of mice. A glucose tolerance test was performed, and fasting blood sugar was tested prior to surgery to verify hyperglycemia. Neurologic deficit score (NDS) was measured before and after surgery, and 24 hours post MCAO.
Results:
HFD fed mice demonstrated worse NDS following ischemia compared to normal fed mice. This was significant at 24 hours post MCAO (p<0.0001). Normal fed mice showed improvement in functional score 24 hours post MCAO (p<0.05), but HFD fed mice demonstrated no improvement.
Conclusion:
Our data show that HFD fed mice have worse outcomes post-MCAO and without the recovery in functional scores seen in normal fed mice. This mirrors the human condition, where worse clinical outcomes are seen in hyperglycemic patients with ischemic stroke. This model provides an opportunity to investigate mechanisms underlying differential recovery in the setting of hyperglycemia and to test if insulin treatment can prevent the adverse recovery in HFD animals as has been postulated in humans. We are conducting gene expression experiments to test candidates that may mediate ischemic damage and recovery and to identify novel therapeutic targets.
Advanced Telemedicine Training and Clinical Outcomes in Type II Diabetes: A Pilot Study
