Persistent increase of Nogo-A-positive cells and dynamic reduction in oligodendroglia lineage cells in white matter regions following experimental and clinical traumatic brain injury
(2025) In Journal of Neuropathology and Experimental Neurology 84(5). p.423-435- Abstract
White matter (WM) disruption and atrophy is a consequence of traumatic brain injury (TBI) and contributes to persisting cognitive impairment. An increased expression of the myelin-associated axonal outgrowth inhibitor Nogo-A and oligodendrocyte pathology might be negatively associated with postinjury WM changes. Here, we analyzed brain tissue from severe TBI patients, obtained by surgical decompression in the early postinjury phase and postmortem brain tissue of long-term TBI survivors and observed an increased number of Nogo-A+ cells in WM tracts such as the corpus callosum (CC). Likewise, the number of Nogo-A+ cells in the CC was increased from day 7 postinjury to 6 months postinjury (mpi) following central fluid... (More)
White matter (WM) disruption and atrophy is a consequence of traumatic brain injury (TBI) and contributes to persisting cognitive impairment. An increased expression of the myelin-associated axonal outgrowth inhibitor Nogo-A and oligodendrocyte pathology might be negatively associated with postinjury WM changes. Here, we analyzed brain tissue from severe TBI patients, obtained by surgical decompression in the early postinjury phase and postmortem brain tissue of long-term TBI survivors and observed an increased number of Nogo-A+ cells in WM tracts such as the corpus callosum (CC). Likewise, the number of Nogo-A+ cells in the CC was increased from day 7 postinjury to 6 months postinjury (mpi) following central fluid percussion injury (cFPI) in mice. In addition, the number of Olig2+ cells in the CC and capsula externa remained constant, while the numbers of Olig2+/CC1+ and GST-π+ mature oligodendrocytes declined throughout the observation time of 18 months. A significantly lower number of Olig2+/CC1+ cells was found in cFPI mice compared to controls at 18 mpi. Persistent vulnerability of oligodendrocytes in combination with dynamic alterations of Nogo-A expression may have implications for the WM atrophy and insufficient recovery observed after TBI.
(Less)
- author
- Ruscher, Karsten
LU
; Michalettos, Georgios
LU
; Abu Hamdeh, Sami
; Clausen, Fredrik
LU
; Nolan, Amber L.
; Flygt, Johanna
; Özen, Ilknur
LU
and Marklund, Niklas
LU
- organization
- publishing date
- 2025-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- central fluid percussion injury, long-term recovery, Nogo-A, oligodendrocyte, traumatic brain injury
- in
- Journal of Neuropathology and Experimental Neurology
- volume
- 84
- issue
- 5
- pages
- 13 pages
- publisher
- American Association of Neuropathologists
- external identifiers
-
- scopus:105003481532
- pmid:40085014
- ISSN
- 0022-3069
- DOI
- 10.1093/jnen/nlaf017
- language
- English
- LU publication?
- yes
- id
- 7ce469e0-159f-4efe-898d-aaa91e3753a1
- date added to LUP
- 2025-08-05 11:06:50
- date last changed
- 2025-08-06 03:00:07
@article{7ce469e0-159f-4efe-898d-aaa91e3753a1, abstract = {{<p>White matter (WM) disruption and atrophy is a consequence of traumatic brain injury (TBI) and contributes to persisting cognitive impairment. An increased expression of the myelin-associated axonal outgrowth inhibitor Nogo-A and oligodendrocyte pathology might be negatively associated with postinjury WM changes. Here, we analyzed brain tissue from severe TBI patients, obtained by surgical decompression in the early postinjury phase and postmortem brain tissue of long-term TBI survivors and observed an increased number of Nogo-A<sup>+</sup> cells in WM tracts such as the corpus callosum (CC). Likewise, the number of Nogo-A<sup>+</sup> cells in the CC was increased from day 7 postinjury to 6 months postinjury (mpi) following central fluid percussion injury (cFPI) in mice. In addition, the number of Olig2<sup>+</sup> cells in the CC and capsula externa remained constant, while the numbers of Olig2<sup>+</sup>/CC1<sup>+</sup> and GST-π<sup>+</sup> mature oligodendrocytes declined throughout the observation time of 18 months. A significantly lower number of Olig2<sup>+</sup>/CC1<sup>+</sup> cells was found in cFPI mice compared to controls at 18 mpi. Persistent vulnerability of oligodendrocytes in combination with dynamic alterations of Nogo-A expression may have implications for the WM atrophy and insufficient recovery observed after TBI.</p>}}, author = {{Ruscher, Karsten and Michalettos, Georgios and Abu Hamdeh, Sami and Clausen, Fredrik and Nolan, Amber L. and Flygt, Johanna and Özen, Ilknur and Marklund, Niklas}}, issn = {{0022-3069}}, keywords = {{central fluid percussion injury; long-term recovery; Nogo-A; oligodendrocyte; traumatic brain injury}}, language = {{eng}}, number = {{5}}, pages = {{423--435}}, publisher = {{American Association of Neuropathologists}}, series = {{Journal of Neuropathology and Experimental Neurology}}, title = {{Persistent increase of Nogo-A-positive cells and dynamic reduction in oligodendroglia lineage cells in white matter regions following experimental and clinical traumatic brain injury}}, url = {{http://dx.doi.org/10.1093/jnen/nlaf017}}, doi = {{10.1093/jnen/nlaf017}}, volume = {{84}}, year = {{2025}}, }