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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

Astrocytes in interface areas of varying width exhibit a tiered response to microwires coated with PEG, with or without LPS.
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Figure 4: Astrocytes in interface areas of varying width exhibit a tiered response to microwires coated with PEG, with or without LPS.

Mentions: Figure 4 shows the astrocyte RI at interface areas. For the interface area containing only the microwire, the astrocyte RI for LPS coated wire (RI = 3.33) was significantly higher than PEG coated and LPS + PEG coated wire (PEG RI = 2.59, p = 0.015; LPS + PEG RI = 2.63, p = 0.02). For the interface area containing the wire and extending an adjacent 25 μm, the same pairwise difference were observed, but with a stronger difference between the LPS coated wire (RI = 6.7) and the LPS + PEG coated wire (PEG RI = 5.75, p = 0.012; LPS + PEG RI = 5.64, p = 0.0045). For the interface area containing the microwire and extending an adjacent 50 μm, the same observation of the LPS astrocyte RI being higher than both PEG and LPS + PEG was noticed (LPS RI = 7.54, PEG RI = 6.49, p = 0.02; LPS + PEG RI = 6.19, p = 0.002). Overall the astrocytes show a similar pattern in the interface as the microglia, but to a lesser extent. Importantly, for all three interface sizes (at the wire, within 25 μm of the wire, and within 50 μm of the wire), the PEG coating is able to significantly reduce the LPS-induced astrocyte response.


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)

Astrocytes in interface areas of varying width exhibit a tiered response to microwires coated with PEG, with or without LPS.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Astrocytes in interface areas of varying width exhibit a tiered response to microwires coated with PEG, with or without LPS.
Mentions: Figure 4 shows the astrocyte RI at interface areas. For the interface area containing only the microwire, the astrocyte RI for LPS coated wire (RI = 3.33) was significantly higher than PEG coated and LPS + PEG coated wire (PEG RI = 2.59, p = 0.015; LPS + PEG RI = 2.63, p = 0.02). For the interface area containing the wire and extending an adjacent 25 μm, the same pairwise difference were observed, but with a stronger difference between the LPS coated wire (RI = 6.7) and the LPS + PEG coated wire (PEG RI = 5.75, p = 0.012; LPS + PEG RI = 5.64, p = 0.0045). For the interface area containing the microwire and extending an adjacent 50 μm, the same observation of the LPS astrocyte RI being higher than both PEG and LPS + PEG was noticed (LPS RI = 7.54, PEG RI = 6.49, p = 0.02; LPS + PEG RI = 6.19, p = 0.002). Overall the astrocytes show a similar pattern in the interface as the microglia, but to a lesser extent. Importantly, for all three interface sizes (at the wire, within 25 μm of the wire, and within 50 μm of the wire), the PEG coating is able to significantly reduce the LPS-induced astrocyte response.

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