KINDLING ELECTRODES IN THE BRAIN CAUSE CHRONIC CELLULAR REACTIVE RESPONSES
Abstract number :
1.112
Submission category :
Year :
2003
Submission ID :
654
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Karen L. Smith, Russell E. Berger, Seung Jae Oh, William Shain, Jeffrey H. Goodman Wadsworth Center-Briggs Labs, NYS Dept. of Health, Albany, NY; Ctr Neural Recovery and Rehab Research, Helen Hayes Hospital, West Haverstraw, NY; Nanobioelectronics and Sys
Electrical stimulation of the brain may provide an important new therapy for epilepsy. There is evidence that low frequency stimulation (LFS) can effectively prevent or decrease seizure activity in patients with epilepsy and in experimental seizure models. An important requirement of any new therapy is that it be safe with a low potential for side effects. The experiments reported here look at the cellular reactive responses associated with chronic implantation of bipolar wire stimulating electrodes verses silicon fabricated neural prosthetic devices.
Devices were implanted into the hippocampus of adult male Sprague Dawley rats. Animals implanted with silicon devices (50x120[mu]m) did not receive any stimulation. Animals with bipolar teflon-coated stainless steel electrodes (125x250[mu]m) received 1Hz, 50[mu]A LFS for different durations (no stimulation, 30 sec, and 5 min). At set time points, the animals were anesthetized and perfusion-fixed with 4% paraformaldehyde, brains were post-fixed for 24-72 hours and vibratome sections made. The tissue slices were stained for Nissl, Fluorojade B, and immunohistochemistry was conducted for NPY, GFAP, phosphorylated SAPK/JNK, caspase 3 and caspase 9. Samples were imaged using a standard inverted fluorescent microscope and a scanning confocal microscope.
Implantation of wire electrodes and silicon neuroprosthetic devices without stimulation produced similar reactive responses around the shank of the devices and at the tip. In summary, hypertrophy of astrocytes with increased expression of GFAP, apoptosis, and stress-related expression of phosphorylated SAPK/JNK were seen in the tissue adjacent to the entire shank of the electrodes. Upregulation of MAP kinase SAPK/JNK has been detected in neurons and glia surrounding the insertion site. In the hippocampus, at the time points tested, Fluorojade B and NPY remained at control levels.
The results indicate similar reactive cellular responses are seen surrounding both devices independent of the materials used for device fabrication. Since phosphorylated SAPK/JNK is upregulated in neurons, device insertion and stimulation may effect overall neuronal function.
[Supported by: NIBIB -RO1EB00359, Dr. J. Goodman-NeuroPace Inc. and The CURE Foundation]