Resveratrol protects neurons from cannulae implantation injury: implications for deep brain stimulation.
Brain-implantable electrodes such as those used in deep brain stimulation (DBS) have a promising future in end-stage Parkinson's disease therapy. However, there is considerable injury when electrodes penetrate brain tissue. For instance, broken blood vessels and glial scar formation may impede continual DBS or electrical recording from specific neurons. To begin addressing this key safety issue, we tested the therapeutic potential of resveratrol in reducing brain trauma caused by DBS-like surgery. Microinfusion of resveratrol (10 μM) directly applied to the sub-thalamic nucleus (STN) of the rat brain significantly minimized the formation of astrocytic gliosis in response to a 27-G precision-glide cannula implant. The therapeutic effects of resveratrol extended to the "kill zone", a boundary zone of about 100 μm comprising the cannula implant and surrounding neurons. We also found that resveratrol not only provided almost complete protection from mechanical injury to the brain, but that it also prevented undesirable motor deficits often seen in animals with lesions to the STN. Lastly, continuous infusion of resveratrol over a 4-week period led to the inhibition of pro-apoptotic, neurodegenerative and cell division cycle genes that may be associated with a reduction in astrocytic gliosis and glial scar formation within the STN. Taken together, these data suggest that application of resveratrol to the brain is an effective adjunct surgical procedure for minimizing acute neuronal injury when electrodes are implanted directly into the STN.
Department of Biology and Neuroscience Program, Hope College, Holland, MI 49422, USA.
J P
JP
Constant
G S
GS
Fraley
E
E
Forbes
B H
BH
Hallas
J R
JR
Leheste
G
G
Torres
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology; D002404:Catheterization / Q000009:adverse effects*; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004567:Electrodes, Implanted / Q000009:adverse effects*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D016133:Polymerase Chain Reaction; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D020531:Subthalamic Nucleus / Q000473:pathology
D000975:Antioxidants; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D013267:Stilbenes; C435731:fluoro jade; D000077185:Resveratrol; D004121:Dimethyl Sulfoxide