Abstracts

RATIONALE: With the objective of developing biosensors that could be implanted into the brain for indefinite periods of time, the present study aimed to determine the extent to which different materials induced a gliotic reaction in brain following long-term implantation. In particular, we are interested in determining the extent to which brain implants may be encapsulated by a glial reaction that would isolate them from the surrounding parenchyma.
METHODS: Carbon, silicon, gold, platinum, or Pyrex needles, 0.5 mm in diameter, were implanted into the hippocampi of adult rats. To simulate trauma, a gold needle was implanted in the hippocampus, tapped 10 times and extracted. On post-operative day 14, the rats were perfused with 4% paraformaldehyde, implants were removed and tissue sections were then immunostained for GFAP. Mean optical density (MOD) measurements were taken of 2000 [mu]m² regions in: 1) the corpus callosum and; 2) three zones adjacent to the implant track (Zones 1, 2, and 3 within 100, 200, and 300 [mu]m of implant track, respectively). Ratios of MOD in the corpus callosum to MOD in each of the three zones were calculated. For control and trauma samples the MOD of four 2000 [mu]m² regions corresponding to the hippocampal implant sites were taken and averaged. Using this average, a ratio of MOD in the corpus callosum to MOD in the hippocampus was calculated. MOD ratios, rather than the absolute MOD values, were used for comparisons to adjust for varying intensities of staining between samples.
RESULTS: Platinum, gold, carbon, silicon, and Pyrex implants resulted in different average MOD ratios. Platinum showed the lowest staining, followed in increasing level by gold, carbon, silicon, and Pyrex. Average MOD ratios for each of the implanted materials were higher than that of controls and of simulated trauma. The MOD ratio of staining decreased at 200 [mu]m and 300 [mu]m radii from brain-implant boundary for each implant material. However, the average MOD ratio for each material remained higher than control at 300 [mu]m. The astrocytic process capsule that formed at the site of the Pyrex implant was porous with some gaps measuring greater than 50 [mu]m in diameter.
CONCLUSIONS: Implantation of materials into the hippocampus induces a glial reaction independent of the trauma incurred during implantation. Platinum appears to cause the least gliosis followed by gold, carbon, silicon, and Pyrex. The increased number of astrocytes seen within 100 [mu]m of the brain-implant boundary at 14 days tapers at increasing distance from the boundary but is still higher than normal at 300 [mu]m. Despite this reaction, the glial boundary which may form at the interface with an implanted device is porous suggesting that a biosensor implanted in the hippocampus would still have adequate communication with the parenchyma after 14 days of implantation.
Support: Clinical Neuroscience Mental Health Research Training Grant (Yale University School of Medicine) and NIH NS38287.