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Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts

Flygt, Johanna; Clausen, Fredrik and Marklund, Niklas LU (2017) In Restorative Neurology and Neuroscience 35(2). p.251-263
Abstract

BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI.

OBJECTIVE: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation.

METHODS: Proliferation of OPCs was evaluated in 27 cFPI mice using... (More)

BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI.

OBJECTIVE: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation.

METHODS: Proliferation of OPCs was evaluated in 27 cFPI mice using 5-ethynyl-2'-deoxyuridine (EdU) labeling and a cell proliferation assay at 2 (n = 9), 7 (n = 8) and 21 (n = 10) days post injury (dpi). Sham-injured mice (n = 14) were used as controls. OPC proliferation was quantified by immunohistochemistry using the OPC markers NG2 and Olig2 in several white matter loci including the corpus callosum, external capsule, fimbriae, the internal capsule and cerebral peduncle.

RESULTS: The number of EdU/DAPI/Olig2-positive cells were increased in the cFPI group compared to sham-injured animals at 7 post-injury (dpi; p≤0.05) in the majority of white matter regions. The OPC proliferation had subsided by 21 dpi. The number of EdU/DAPI/NG2 cells was also increase at 7 dpi in the external capsule and fimbriae.

CONCLUSION: These results suggest that traumatic axonal injury in the mouse induces a transient proliferative response of residing OPCs. These proliferating OPCs may replace dead oligodendrocytes and contribute to remyelination, which needs evaluation in future studies.

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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Restorative Neurology and Neuroscience
volume
35
issue
2
pages
251 - 263
publisher
IOS Press
external identifiers
  • scopus:85016263618
ISSN
1878-3627
DOI
10.3233/RNN-160675
language
English
LU publication?
no
id
01684220-b1e4-40dc-bf13-9a0fb4a5e49e
date added to LUP
2016-12-09 15:38:35
date last changed
2018-01-07 11:40:13
@article{01684220-b1e4-40dc-bf13-9a0fb4a5e49e,
  abstract     = {<p>BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI.</p><p>OBJECTIVE: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation.</p><p>METHODS: Proliferation of OPCs was evaluated in 27 cFPI mice using 5-ethynyl-2'-deoxyuridine (EdU) labeling and a cell proliferation assay at 2 (n = 9), 7 (n = 8) and 21 (n = 10) days post injury (dpi). Sham-injured mice (n = 14) were used as controls. OPC proliferation was quantified by immunohistochemistry using the OPC markers NG2 and Olig2 in several white matter loci including the corpus callosum, external capsule, fimbriae, the internal capsule and cerebral peduncle.</p><p>RESULTS: The number of EdU/DAPI/Olig2-positive cells were increased in the cFPI group compared to sham-injured animals at 7 post-injury (dpi; p≤0.05) in the majority of white matter regions. The OPC proliferation had subsided by 21 dpi. The number of EdU/DAPI/NG2 cells was also increase at 7 dpi in the external capsule and fimbriae.</p><p>CONCLUSION: These results suggest that traumatic axonal injury in the mouse induces a transient proliferative response of residing OPCs. These proliferating OPCs may replace dead oligodendrocytes and contribute to remyelination, which needs evaluation in future studies.</p>},
  author       = {Flygt, Johanna and Clausen, Fredrik and Marklund, Niklas},
  issn         = {1878-3627},
  language     = {eng},
  number       = {2},
  pages        = {251--263},
  publisher    = {IOS Press},
  series       = {Restorative Neurology and Neuroscience},
  title        = {Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts},
  url          = {http://dx.doi.org/10.3233/RNN-160675},
  volume       = {35},
  year         = {2017},
}