Submitted to: Society for Neuroscience Abstracts and Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: June 20, 2008
Publication Date: N/A
Technical Abstract: Obesity is a major risk factor for stroke, and tissue injury following a stroke may be more severe in the obese. A key feature of obesity is increased serum levels of obesity-related hormones including leptin and insulin, indicating a state of resistance to these hormones. Insulin resistance is generally associated with leptin resistance. While serum insulin and leptin levels are high in obesity, their levels in the brain are lower possibly due to reduced transport across the blood-brain barrier. Astrocyte (glial cell) swelling is a major component of cytotoxic brain edema in ischemia and can contribute to increased intracranial pressure and brain herniation. C6 glial cell cultures were exposed to oxygen-glucose deprivation (OGD) for 5hr and cell swelling was determined 90 min after the end of OGD using the 3-OMG method. Pre-treatment with leptin (100 ng/ml) before OGD significantly blocked (50%) OGD-induced cell swelling. Insulin (10 µM) added after OGD also significantly diminished cell swelling. A cinnamon extract (CE; 0.01 mg/ml) completely blocked OGD-induced cell swelling. Mitochondrial dysfunction, a key feature of ischemic injury, is hypothesized to play an important role in glial cell swelling. Depolarization of the inner mitochondrial membrane potential (delta psi m) was assessed immediately at the end of OGD using TMRE, a fluorescent dye. The OGD-induced decline in delta psi m was significantly attenuated by leptin, insulin, and CE. Our results indicate that some of the deleterious effects of ischemic injury may be reduced by leptin, insulin, and CE. Dietary polyphenols that improve insulin resistance or leptin resistance may play an important role in reducing cell swelling in ischemic injury.