Resveratrol Ameliorates Brain Damage Induced By Surgical Cannulae: Potential For Treatment Of Parkinson’s Disease

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Dr. Gregory Fraley, Hope College

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During advanced-stage Parkinson’s disease (PD), many patients resort to deep brain stimulation (DBS), a treatment in which electrodes are implanted into the brain. Even though his treatment has proven highly effective for many PD patients, the main side effects are due to a 1 mm3 area of cell death around the electrode. The lesions are due to the physical presence of the electrodes and eventually lead to an ineffectiveness of DBS to ameliorate the signs of PD. Resveratrol (RESV), a plant derivative and antioxidant found in grape skins (specifically in red wine), has shown to have protective effects against cellular degeneration. We previously found that RESV has neuroprotective effects to prevent brain lesions associated with the physical presence of cannulas in the brains of rats. Because of RESV’s estrogenic structure we decided to test the non-classical estrogen receptor GPR30 as a possible mechanism of action of RESV. We used estriol, a known antagonist for GPR30. Peripheral treatments of RESV, RESV/estriol, and blank capsules were implanted prior to surgery. All animals received a unilateral cannula into the subthalamic nucleus (STN), which is the target site in humans undergoing DBS. A rotorod test was used to quantify motor coordination following injections. All rats that received blank or RESV/estriol treatments showed significant (p < 0.01) motor-deficits post-surgery. Neuronal damage was assessed using Nissl stain, GFAP immunocytochemistry (to measure gliosis), and Fluoro-Jade stain for neuronal degeneration. Histology demonstrated that estriol inhibited the neuroprotective effects of RESV. The control and RESV/estriol treatments showed increased gliosis, necrosis, and neuronal degeneration than compared to RESV treatment. Qualitative assessments suggest that RESV-treatment attenuated all of these effects, thus preventing much of the damage associated with cannula placement. Our studies suggest that resveratrol may have neuroprotective effects and that it may in fact be acting through the GPR30 receptor.

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