PMID-24973296 The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.
- Quite good introductory review on current understanding of immune / inflammatory / BBB breakdown response to indwelling neural implants.
- Used chimera mice with marrow from CFP mice transplanted into irradiated hosts, so myeloid cells were labeled (including macrophages and monocytes).
- Details of this process are properly fascinating ... there are clever ways of isolating and selecting the right marrow cells.
- Implanted with a dummy Michigan style probe, 2mm x 123 um x 15um.
- Histological processes and cell sorting / labeling also highly detailed.
- 60% of the infiltrating cells (CFP+) are macrophages.
- Within the total IBA1+ population (macrophages + microglia), we saw that only 20% of the total IBA1+ population was comprised of microglia at two weeks post implantation (Fig. 9G).
- Additionally, at chronic time points (four, eight and sixteen weeks), we observed that less than 40% of the total IBA1+ population was comprised of microglia (Fig. 9G).
- On the other hand, no significant differences were observed in microglia populations over time (Fig. 9G, Table 4). Together, our results suggest a predominant role of infiltrating macrophages surrounding implanted microelectrodes over time.
- IBA1 = marker for ionized calcium binding adapter molecule, to label the total population of microglia/ macrophages (both resting and activated)
- CD68 = activated microglia / macrophage.
- Hard to discriminate microglia and infiltrating macrophages.
- Interestingly, fluctuations in GFAP+ immunoreactivity correlated well with neuronal density and CFP+ immunoreactivty, suggesting a possible role of astrocytes in facilitating trafficking of blood-derived cells.
- Contrary to what has been suggested by many intracortical microelectrode studies, a consistent connection was not found between activated microglia/macrophages and neuron density in our chimera models
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