Peiman Habibollahi MD, Presenter: Nothing to Disclose

Pedram Heidari MD, Abstract Co-Author: Nothing to Disclose

Jeong Hyun Lee, Abstract Co-Author: Nothing to Disclose

Ali Daneshmand, Abstract Co-Author: Nothing to Disclose

Georges El Fakhri PhD, Abstract Co-Author: Nothing to Disclose

Cenk Ayata, Abstract Co-Author: Nothing to Disclose

Umar Mahmood MD, PhD, Abstract Co-Author: Nothing to Disclose

The ischemic penumbra is a dynamic target that evolves over time. In early stages of large artery stroke most infarcts are surrounded by hypoperfused but still viable tissue. Salvage strategies are being explored to keep the at-risk tissue alive. Early studies have suggested that chronic metformin provides a neuroprotective effect. Metformin’s role via AMP kinase in cellular glucose metabolism suggests that FDG PET imaging would be an ideal tool to study its effects in chronic verses acute dosing as an infarct modulator. 

Three groups of male mice (n=6 each) were subjected to middle cerebral artery occlusion after receiving acute (75 mg/kg/day for 3 days), chronic (75 mg/kg/day for 20 days) metformin, or saline treatment. Afterwards, 60 minute dynamic FDG PET imaging was performed and the FDG uptake in the stroke core, adjacent penumbra and contralateral normal brain tissue was measured. Perfusion (early dynamic frames) and glucose extraction fraction (uptake/perfusion) were calculated. 

A significantly higher glucose extraction was seen in the ischemic penumbra compared to contra-lateral normal brain tissue and infracted area (1.72±0.12 vs 0.84±0.11 and 0.46±0.03, respectively, p<0.05). The result was modulated divergently in the acute and chronic metformin treatment groups. Acute metformin treatment increased FDG uptake in the contralateral normal brain hemisphere compared to the chronic group (1.18±0.11 vs 0.73±0.04, p<0.05). Chronic metformin ameliorated increased FDG uptake in ischemic penumbra; seen in acute metformin and control groups (1.01±0.10 vs 1.54±0.03 and 1.69±0.10, respectively, p<0.05). 

These results suggest a possible role for chronic metformin treatment for improving outcome, decreasing infarct size as well as saving the hypoperfused salvageable penumbra through a postulated mechanism centered on glucose utilization. In contradistinction, acute metformin results in increased penumbra glucose utilization.

The developed imaging methods for these experiments are clinically translatable for the evaluation of glucose uptake modifiers in stroke treatment.  

Habibollahi, P, Heidari, P, Lee, J, Daneshmand, A, El Fakhri, G, Ayata, C, Mahmood, U, Chronic vs Acute Metformin Treatment Results in Divergent Glucose Uptake in the Ischemic Penumbra.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11034544.html