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Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury.

Ziebell JM, Taylor SE, Cao T, Harrison JL, Lifshitz J - J Neuroinflammation (2012)

Bottom Line: Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI).Rats were subjected to a moderate midline fluid percussion injury (mFPI), which resulted in transient suppression of their righting reflex (6 to 10 min).Diffuse traumatic brain injury induces a distinct rod microglia morphology, unique phenotype, and novel association between cells; these observations entice further investigation for impact on neurological outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.

ABSTRACT

Background: Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen), which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical 'synaptic stripping' but their exact role has remained unclear. This is due at least in part to a scarcity of experimental models. Now we have noted these rod microglia after experimental diffuse brain injury in brain regions that have an associated sensory sensitivity. Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI).

Methods: Rats were subjected to a moderate midline fluid percussion injury (mFPI), which resulted in transient suppression of their righting reflex (6 to 10 min). Multiple immunohistochemistry protocols targeting microglia with Iba1 and other known microglia markers were undertaken to identify the morphological activation of microglia. Additionally, labeling with Iba1 and cell markers for neurons and astrocytes identified the architecture that surrounds these rod cells.

Results: We identified an abundance of Iba1-positive microglia with rod morphology in the primary sensory barrel fields (S1BF). Although present for at least 4 weeks post mFPI, they developed over the first week, peaking at 7 days post-injury. In the absence of contusion, Iba1-positive microglia appear to elongate with their processes extending from the apical and basal ends. These cells then abut one another and lay adjacent to cytoarchitecture of dendrites and axons, with no alignment with astrocytes and oligodendrocytes. Iba1-positive rod microglial cells differentially express other known markers for reactive microglia including OX-6 and CD68.

Conclusion: Diffuse traumatic brain injury induces a distinct rod microglia morphology, unique phenotype, and novel association between cells; these observations entice further investigation for impact on neurological outcome.

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Rod microglia couple together to form trains. Immunofluorescence labeling of Iba1-positive microglia (red) with the nuclear marker Hoechst (blue) revealed that aligned rod microglia at 7 days post-injury were composed of multiple cells aligned in a single trajectory with their highly polarized processes seemingly intertwined. These rod microglia coupled together to form long trains which spanned multiple cortical layers.
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Figure 3: Rod microglia couple together to form trains. Immunofluorescence labeling of Iba1-positive microglia (red) with the nuclear marker Hoechst (blue) revealed that aligned rod microglia at 7 days post-injury were composed of multiple cells aligned in a single trajectory with their highly polarized processes seemingly intertwined. These rod microglia coupled together to form long trains which spanned multiple cortical layers.

Mentions: Further analysis of the architecture surrounding rod microglia trains was undertaken at day 7 post mFPI; the time point shown to have the greatest cellular alignment. Unlike radial glial cells, which exhibit a single cell body with long projections[22-26], the rod microglia have coupled to form trains consisting of more than one rod microglia cell, as illustrated in Figure3. We use the term coupling to indicate a physical proximity between the apical and basal processes of adjacent rod microglia. Adjacent rod microglia were identified by Hoechst positive staining of separate nuclei.


Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury.

Ziebell JM, Taylor SE, Cao T, Harrison JL, Lifshitz J - J Neuroinflammation (2012)

Rod microglia couple together to form trains. Immunofluorescence labeling of Iba1-positive microglia (red) with the nuclear marker Hoechst (blue) revealed that aligned rod microglia at 7 days post-injury were composed of multiple cells aligned in a single trajectory with their highly polarized processes seemingly intertwined. These rod microglia coupled together to form long trains which spanned multiple cortical layers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3526458&req=5

Figure 3: Rod microglia couple together to form trains. Immunofluorescence labeling of Iba1-positive microglia (red) with the nuclear marker Hoechst (blue) revealed that aligned rod microglia at 7 days post-injury were composed of multiple cells aligned in a single trajectory with their highly polarized processes seemingly intertwined. These rod microglia coupled together to form long trains which spanned multiple cortical layers.
Mentions: Further analysis of the architecture surrounding rod microglia trains was undertaken at day 7 post mFPI; the time point shown to have the greatest cellular alignment. Unlike radial glial cells, which exhibit a single cell body with long projections[22-26], the rod microglia have coupled to form trains consisting of more than one rod microglia cell, as illustrated in Figure3. We use the term coupling to indicate a physical proximity between the apical and basal processes of adjacent rod microglia. Adjacent rod microglia were identified by Hoechst positive staining of separate nuclei.

Bottom Line: Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI).Rats were subjected to a moderate midline fluid percussion injury (mFPI), which resulted in transient suppression of their righting reflex (6 to 10 min).Diffuse traumatic brain injury induces a distinct rod microglia morphology, unique phenotype, and novel association between cells; these observations entice further investigation for impact on neurological outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA.

ABSTRACT

Background: Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen), which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical 'synaptic stripping' but their exact role has remained unclear. This is due at least in part to a scarcity of experimental models. Now we have noted these rod microglia after experimental diffuse brain injury in brain regions that have an associated sensory sensitivity. Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI).

Methods: Rats were subjected to a moderate midline fluid percussion injury (mFPI), which resulted in transient suppression of their righting reflex (6 to 10 min). Multiple immunohistochemistry protocols targeting microglia with Iba1 and other known microglia markers were undertaken to identify the morphological activation of microglia. Additionally, labeling with Iba1 and cell markers for neurons and astrocytes identified the architecture that surrounds these rod cells.

Results: We identified an abundance of Iba1-positive microglia with rod morphology in the primary sensory barrel fields (S1BF). Although present for at least 4 weeks post mFPI, they developed over the first week, peaking at 7 days post-injury. In the absence of contusion, Iba1-positive microglia appear to elongate with their processes extending from the apical and basal ends. These cells then abut one another and lay adjacent to cytoarchitecture of dendrites and axons, with no alignment with astrocytes and oligodendrocytes. Iba1-positive rod microglial cells differentially express other known markers for reactive microglia including OX-6 and CD68.

Conclusion: Diffuse traumatic brain injury induces a distinct rod microglia morphology, unique phenotype, and novel association between cells; these observations entice further investigation for impact on neurological outcome.

Show MeSH
Related in: MedlinePlus