CRB, a Resveratrol Analog, Reduces Cell Injury Caused by Surgery Mimicking Deep Brain Stimulation
Research funded by a grant from the Campbell Foundation.
Abstract
Brain-implantable devices such as those used in deep brain stimulation (DBS) have a promising future in end-stage Parkinson’s disease. However, inserting electrodes into the brain can cause astrocytic gliosis, inflammation and cell dystrophy, which is a major source of failure in chronically implantable electrodes. It is known from previous experiments that resveratrol significantly reduced tissue damage caused by DBS, however, because the metabolic half-life of resveratrol is short, an analog with longer biological activity is necessary. Our main hypothesis in this study is to test the effectiveness of CRB, a synthetic analog of resveratrol, on reducing tissue damage caused by DBS. We stereotaxically delivered CRB into the rat sub-thalamic nucleus (STN) bilaterally. We compared a 10 µM dose of CRB to both vehicle (DMSO) microinjections and resveratrol injections aimed at the STN bilaterally (n = 8 per treatment). Rotarod testing was performed prior to surgery and 48 hours, 1 week, and 2 weeks post surgery. The animals injected with CRB demonstrated an increase in motor coordination from the pre-surgery trials similar to the animals treated with resveratrol. Both resveratrol and CRB treatment groups showed significantly (p = 0.05) improved motor coordination compared to the vehicle controls. These observations suggest that CRB is a promising treatment to prevent neuronal damage inflicted by DBS. Histological analyses will ensue to determine if the behavioral effects of CRB are due to prevention of scarring and gliosis following surgery. Data suggest that a synthetic resveratrol analog may have similar neuroprotective effects as similar to those of resveratrol itself.
