Limits...
Glial cells, but not neurons, exhibit a controllable response to a localized inflammatory microenvironment in vitro.

Sommakia S, Rickus JL, Otto KJ - Front Neuroeng (2014)

Bottom Line: Astrocytes exhibit a more complex, distance-dependent response, whereas neurons do not appear to be affected by the type or magnitude of glial response within this in vitro model.The discrepancy between our in vitro responses and typically observed in vivo responses suggest the importance of using a systems approach to understand the responses of the various brain cell types in a chronic in vivo setting, as well as the necessity of studying the roles of cell types not native to the brain.Our results further indicate that the loss of neuronal density observed in vivo is not a necessary consequence of elevated glial activation.

View Article: PubMed Central - PubMed

Affiliation: Weldon School of Biomedical Engineering, Purdue University West Lafayette, IN, USA ; Physiological Sensing Facility at the Bindley Bioscience Center and Birck Nanotechnology Center, Purdue University West Lafayette, IN, USA.

ABSTRACT
The ability to design long-lasting intracortical implants hinges on understanding the factors leading to the loss of neuronal density and the formation of the glial scar. In this study, we modify a common in vitro mixed cortical culture model using lipopolysaccharide (LPS) to examine the responses of microglia, astrocytes, and neurons to microwire segments. We also use dip-coated polyethylene glycol (PEG), which we have previously shown can modulate impedance changes to neural microelectrodes, to control the cellular responses. We find that microglia, as expected, exhibit an elevated response to LPS-coated microwire for distances of up to 150 μm, and that this elevated response can be mitigated by co-depositing PEG with LPS. Astrocytes exhibit a more complex, distance-dependent response, whereas neurons do not appear to be affected by the type or magnitude of glial response within this in vitro model. The discrepancy between our in vitro responses and typically observed in vivo responses suggest the importance of using a systems approach to understand the responses of the various brain cell types in a chronic in vivo setting, as well as the necessity of studying the roles of cell types not native to the brain. Our results further indicate that the loss of neuronal density observed in vivo is not a necessary consequence of elevated glial activation.

No MeSH data available.


Related in: MedlinePlus

Microglial response to LPS-coated microwire compared to all other treatments is elevated at distances up to 150 μm, after which a tiered response is observed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231942&req=5

Figure 3: Microglial response to LPS-coated microwire compared to all other treatments is elevated at distances up to 150 μm, after which a tiered response is observed.

Mentions: Figure 3 shows the microglial responses at more distant regions. For the closest distant bin extending from 50 to 150 μm from edge of wire, the RI for LPS coated wire (RI = 5.62) was significantly higher than all the other treatments (uncoated RI = 4.21, p = 0.0001; PEG RI = 3.71, p < 0.0001; LPS + PEG RI = 3.91, p < 0.0001). For the next three distant 100 μm wide bins, the only significant difference observed was between LPS coated wire and PEG coated wire in all 3 bins. These calculated RI are as follows: for the bin extending from 150 to 250 μm from edge of wire: LPS RI = 4.5 vs. PEG 3.12, p = 0.0001; for the bin extending 250–350 μm from edge of wire: RI = 5.12 vs. 3.8, p = 0.0003; for the bin extending 350–450 μm from edge of wire): RI = 4.98 vs. 3.9, p = 0.01. Again the pattern of relative RI’s is consistent at all distances in the distant regions and matches that of the interface region. In this case the size of each measurement area is the same across cases and is always 100 microns. Again LPS induces an increased RI in all regions reaching statistical significance when comparing LPS to the PEG coated wire and in the most near distant region (50–150 microns) when comparing LPS to an uncoated wire. The wire likely induces some basal level of microglial attachment or activation, which is reduced by PEG alone, therefore the effect of LPS is most pronounced when we compare the PEG wire. These results are consistent with a diffusion based model whereby the effect of LPS will decrease with increasing distance from the wire.


Glial cells, but not neurons, exhibit a controllable response to a localized inflammatory microenvironment in vitro.

Sommakia S, Rickus JL, Otto KJ - Front Neuroeng (2014)

Microglial response to LPS-coated microwire compared to all other treatments is elevated at distances up to 150 μm, after which a tiered response is observed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231942&req=5

Figure 3: Microglial response to LPS-coated microwire compared to all other treatments is elevated at distances up to 150 μm, after which a tiered response is observed.
Mentions: Figure 3 shows the microglial responses at more distant regions. For the closest distant bin extending from 50 to 150 μm from edge of wire, the RI for LPS coated wire (RI = 5.62) was significantly higher than all the other treatments (uncoated RI = 4.21, p = 0.0001; PEG RI = 3.71, p < 0.0001; LPS + PEG RI = 3.91, p < 0.0001). For the next three distant 100 μm wide bins, the only significant difference observed was between LPS coated wire and PEG coated wire in all 3 bins. These calculated RI are as follows: for the bin extending from 150 to 250 μm from edge of wire: LPS RI = 4.5 vs. PEG 3.12, p = 0.0001; for the bin extending 250–350 μm from edge of wire: RI = 5.12 vs. 3.8, p = 0.0003; for the bin extending 350–450 μm from edge of wire): RI = 4.98 vs. 3.9, p = 0.01. Again the pattern of relative RI’s is consistent at all distances in the distant regions and matches that of the interface region. In this case the size of each measurement area is the same across cases and is always 100 microns. Again LPS induces an increased RI in all regions reaching statistical significance when comparing LPS to the PEG coated wire and in the most near distant region (50–150 microns) when comparing LPS to an uncoated wire. The wire likely induces some basal level of microglial attachment or activation, which is reduced by PEG alone, therefore the effect of LPS is most pronounced when we compare the PEG wire. These results are consistent with a diffusion based model whereby the effect of LPS will decrease with increasing distance from the wire.

Bottom Line: Astrocytes exhibit a more complex, distance-dependent response, whereas neurons do not appear to be affected by the type or magnitude of glial response within this in vitro model.The discrepancy between our in vitro responses and typically observed in vivo responses suggest the importance of using a systems approach to understand the responses of the various brain cell types in a chronic in vivo setting, as well as the necessity of studying the roles of cell types not native to the brain.Our results further indicate that the loss of neuronal density observed in vivo is not a necessary consequence of elevated glial activation.

View Article: PubMed Central - PubMed

Affiliation: Weldon School of Biomedical Engineering, Purdue University West Lafayette, IN, USA ; Physiological Sensing Facility at the Bindley Bioscience Center and Birck Nanotechnology Center, Purdue University West Lafayette, IN, USA.

ABSTRACT
The ability to design long-lasting intracortical implants hinges on understanding the factors leading to the loss of neuronal density and the formation of the glial scar. In this study, we modify a common in vitro mixed cortical culture model using lipopolysaccharide (LPS) to examine the responses of microglia, astrocytes, and neurons to microwire segments. We also use dip-coated polyethylene glycol (PEG), which we have previously shown can modulate impedance changes to neural microelectrodes, to control the cellular responses. We find that microglia, as expected, exhibit an elevated response to LPS-coated microwire for distances of up to 150 μm, and that this elevated response can be mitigated by co-depositing PEG with LPS. Astrocytes exhibit a more complex, distance-dependent response, whereas neurons do not appear to be affected by the type or magnitude of glial response within this in vitro model. The discrepancy between our in vitro responses and typically observed in vivo responses suggest the importance of using a systems approach to understand the responses of the various brain cell types in a chronic in vivo setting, as well as the necessity of studying the roles of cell types not native to the brain. Our results further indicate that the loss of neuronal density observed in vivo is not a necessary consequence of elevated glial activation.

No MeSH data available.


Related in: MedlinePlus