, 1981). It is possible that due to these culture conditions that astrocyte response is altered Gefitinib solubility from normally developing astrocytes in vivo. Neurons No significant differences were detected in neuron response to any of the treatments, in either interface or distant regions. While not statistically significant, a coupling between neuron and astrocyte response can be noticed, where slightly higher (but not significantly different)

neuron growth was observed for the LPS treatment. Neuronal growth has been consistently shown to occur on a supporting substrate of astrocytes (Noble et al., 1984; Tomaselli et al., 1988). In contrast to the microglia and astrocytes, where the response in the widest interface bin was considerably higher than the first adjacent distant bin, the neuron RI in the first distant bin was comparable to the neuron RI in the wide interface bin, and we did not observe a decline in neuron density over distance. One explanation mirrors the concern expressed earlier about the maturity of the astrocytes, where immature astrocytes in culture provided a better substrate for neuron outgrowth compared to mature astrocytes (Smith et al., 1990). An alternative explanation is that elevated glial activation is not in and of itself neurotoxic or neurodegenerative within a foreign body reactive tissue response paradigm.

If the latter explanation is correct, then the loss of neural density in vivo following implantation of a microelectrode might be better explained by displacement of neurons following insertion trauma and edema which fail to reoccupy depleted zones because of the glial scar formation, or that in vivo neurotoxicity occurs due to direct contact between neurons and extrabrain

components. Conclusions We have shown that microglial response in a primary mixed cortical culture can be manipulated by dip-coated treatments. Microglial response can be increased by coating the surface of the foreign body with LPS, and this increase can be prevented by co-depositing LPS and PEG. We hypothesize that the film of high molecular weight PEG, while allowing for LPS release, presents a hydrated physical barrier that disrupts cytokine, chemokine and adsorbed protein gradients that typically guide pathological responses. Astrocyte response also AV-951 increased for LPS coated foreign bodies, but it is unclear whether this response is directly mediated by LPS or whether it is caused by other microglia-secreted factors. Neuron response was not negatively correlated with microglial response, suggesting mechanisms other than glial activation causing in vivo neuronal density loss. Our results highlight the importance of considering the in vivo chronic foreign body response as a complex phenomenon with multiple, interconnected yet parallel processes.