Cerebral astrocyte response to micromachined silicon implants.
The treatment of neurologic disorders and the restoration of lost function due to trauma by neuroprosthetic devices has been pursued for over 20 years. The methodology for fabricating miniature devices with sophisticated electronic functions to interface with nervous system tissue is available, having been well established by the integrated circuit industry. Unfortunately, the effectiveness of these devices is severely limited by the tissue reaction to the insertion and continuous presence of the implant, a foreign object. This study was designed to document the response of reactive astrocytes in the hope that this information will be useful in specifying new fabrication technologies and devices capable of prolonged functioning in the brain. Model probes fabricated from single crystal silicon wafers were implanted into the cerebral cortices of rats. The probes had a 1 x 1-mm tab, for handling, and a 2-mm-long shaft with a trapezoidal cross-section (200-microm base, 60microm width at the top, and 130 microm height). The tissue response was studied by light and scanning electron microscopy at postinsertion times ranging from 2 to 12 weeks. A continuous sheath of cells was found to surround the insertion site in all tissue studied and was well developed but loosely organized at 2 weeks. By 6 and 12 weeks, the sheath was highly compacted and continuous, isolating the probe from the brain. At 2 and 4 weeks, the sheath was disrupted when the probe was removed from the fixed tissue, indicating that cells attached more strongly to the surface of the probe than to the nearby tissue. The later times showed much less disruption. Scanning electron microscopy of the probes showed adherent cells or cell fragments at all time points. Thus, as the sheath became compact, the cells on the probe and the cells in the sheath had decreased adhesion to each other. Immunocytochemistry demonstrated that the sheath was labeled with antibodies to glial fibrillary acidic protein (GFAP), an indicator for reactive gliosis. The tissue surrounding the insertion site showed an increased number of GFAP-positive cells which tended to return to control levels as a function of time after probe insertion. It was concluded that reactive gliosis is an important part of the process forming the cellular sheath. Further, the continuous presence of the probe appears to result in a sustained response that produces and maintains a compact sheath, at least partially composed of reactive glia, which isolates the probe from the brain.
Turner
J N
JN
Wadsworth Center, New York State Department of Health, Albany, New York 12201-0509, USA.
Shain
W
W
Szarowski
D H
DH
Andersen
M
M
Martins
S
S
Isaacson
M
M
Craighead
H
H
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology; D001672:Biocompatible Materials / Q000009:adverse effects; D002448:Cell Adhesion; D002540:Cerebral Cortex / Q000166:cytology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008904:Miniaturization; D019736:Prostheses and Implants / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000009:adverse effects*
D001672:Biocompatible Materials; D005904:Glial Fibrillary Acidic Protein; D012822:Silicon Dioxide