Minocycline increases quality and longevity of chronic neural recordings

Abstract

Brain/machine interfaces could potentially be used in the treatment of a host of neurological disorders ranging from paralysis to sensory deficits. Insertion of chronic micro-electrode arrays into neural tissue initiates a host of immunological responses, which typically leads to the formation of a cellular sheath around the implant, resulting in the loss of useful signals. Minocycline has been shown to have neuroprotective and neurorestorative effects in certain neural injury and neurodegenerative disease models. This study examined the effects of minocycline administration on the quality and longevity of chronic multi-channel microwire neural implants 1 week and 1 month post-implantation in auditory cortex. The mean signal-to-noise ratio for the minocycline group stabilized at the end of week 1 and remained above 4.6 throughout the following 3 weeks. The control group signal-to-noise ratio dropped throughout the duration of the study and at the end of 4 weeks was 2.6. Furthermore, 68% of electrodes from the minocycline group showed significant stimulus-driven activity at week 4 compared to 12.5% of electrodes in the control group. There was a significant reduction in the number of activated astrocytes around the implant in minocycline subjects, as well as a reduction in total area occupied by activated astrocytes at 1 and 4 weeks.

Figure 1

SNR data. There were no significant differences between the groups during the first 6 days. On day 7, the control group SNR decreased significantly, while the minocycline group did not change. Error bars are the 95% confidence interval. (*p < 0.05, ***p < 0.001)

Figure 2

Per cent of driven channels. The per cent of channels with driven activity was measured for each subject. The control group has a steady decline over the 4 week period while the minocycline group stays relatively stable across 4 weeks. Error bars are 95% confidence interval. (*p < 0.05)

Figure 3

Histology images. Panels (A)–(D) display representative examples of histology at 1 week. The minocycline group ((A) and (B)) displayed fewer activated cells and covered a smaller area than the controls ((C) and (D)). The 4 week data are presented in (E)–(H). At 4 weeks the two groups look very similar. The figures in the right column are the threshold figures used to count the number and size of cells. (This figure is in colour only in the electronic version)

Figure 4

Quantitative histology. Using automated image analysis software (ImageJ), the area occupied by each cell, the total number of activated cells and the total area occupied by activated astrocytes were measured. The 1 week data are presented in the left column and the 4 week data are in the right column. At both 1 and 4 weeks, the control group exhibited an increase in the total number of activated astrocytes and the total area occupied by these cells. However, the activated astrocyte size was larger in the minocycline group at week 1 only. Error bars are 95% confidence interval. (*p < 0.05; ***p < 0.001).