Advanced

Neutralization of Interleukin-1β following Diffuse Traumatic Brain Injury in the Mouse Attenuates the Loss of Mature Oligodendrocytes

Flygt, Johanna ; Ruscher, Karsten LU ; Norberg, Amanda ; Mir, Anis ; Gram, Hermann ; Clausen, Fredrik and Marklund, Niklas LU (2018) In Journal of Neurotrauma 35(23). p.2837-2849
Abstract

Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1β (IL-1β) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. To evaluate the role of IL-1β on oligodendrocyte cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at two, seven, and 14 days post-injury. At 30 min... (More)

Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1β (IL-1β) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. To evaluate the role of IL-1β on oligodendrocyte cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at two, seven, and 14 days post-injury. At 30 min post-injury, mice were randomly administered an IL-1β neutralizing or a control antibody. OPC proliferation (5-ethynyl 2'- deoxyuridine (EdU)/Olig2 co-labeling) and mature oligodendrocyte cell loss was evaluated in injured white matter tracts. Microglia/macrophages immunohistochemistry and ramification using Sholl analysis were also evaluated. Neutralizing IL-1β resulted in attenuated cell death, indicated by cleaved caspase-3 expression, and attenuated loss of mature OLs from two to seven days post-injury in brain-injured animals. IL-1β neutralization also attenuated the early, two day post-injury increase of microglia/macrophage immunoreactivity and altered their ramification. The proliferation of OPCs in brain-injured animals was not altered, however. Our data suggest that IL-1β is involved in the TBI-induced loss of OLs and early microglia/macrophage activation, although not the OPC proliferation. Attenuated oligodendrocyte cell loss may contribute to the improved behavioral outcome observed by IL-1β neutralization in this mouse model of diffuse TBI.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neurotrauma
volume
35
issue
23
pages
2837 - 2849
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:29690837
  • scopus:85052286305
ISSN
1557-9042
DOI
10.1089/neu.2018.5660
language
English
LU publication?
yes
id
2e9ffed0-3b1b-4a0f-890d-9d2f56ef3819
date added to LUP
2018-09-13 15:23:25
date last changed
2020-12-01 04:23:47
@article{2e9ffed0-3b1b-4a0f-890d-9d2f56ef3819,
  abstract     = {<p>Traumatic brain injury (TBI) commonly results in injury to the components of the white matter tracts, causing post-injury cognitive deficits. The myelin-producing oligodendrocytes (OLs) are vulnerable to TBI, although may potentially be replaced by proliferating oligodendrocyte progenitor cells (OPCs). The cytokine interleukin-1β (IL-1β) is a key mediator of the complex inflammatory response, and when neutralized in experimental TBI, behavioral outcome was improved. To evaluate the role of IL-1β on oligodendrocyte cell death and OPC proliferation, 116 adult male mice subjected to sham injury or the central fluid percussion injury (cFPI) model of traumatic axonal injury, were analyzed at two, seven, and 14 days post-injury. At 30 min post-injury, mice were randomly administered an IL-1β neutralizing or a control antibody. OPC proliferation (5-ethynyl 2'- deoxyuridine (EdU)/Olig2 co-labeling) and mature oligodendrocyte cell loss was evaluated in injured white matter tracts. Microglia/macrophages immunohistochemistry and ramification using Sholl analysis were also evaluated. Neutralizing IL-1β resulted in attenuated cell death, indicated by cleaved caspase-3 expression, and attenuated loss of mature OLs from two to seven days post-injury in brain-injured animals. IL-1β neutralization also attenuated the early, two day post-injury increase of microglia/macrophage immunoreactivity and altered their ramification. The proliferation of OPCs in brain-injured animals was not altered, however. Our data suggest that IL-1β is involved in the TBI-induced loss of OLs and early microglia/macrophage activation, although not the OPC proliferation. Attenuated oligodendrocyte cell loss may contribute to the improved behavioral outcome observed by IL-1β neutralization in this mouse model of diffuse TBI.</p>},
  author       = {Flygt, Johanna and Ruscher, Karsten and Norberg, Amanda and Mir, Anis and Gram, Hermann and Clausen, Fredrik and Marklund, Niklas},
  issn         = {1557-9042},
  language     = {eng},
  number       = {23},
  pages        = {2837--2849},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Neurotrauma},
  title        = {Neutralization of Interleukin-1β following Diffuse Traumatic Brain Injury in the Mouse Attenuates the Loss of Mature Oligodendrocytes},
  url          = {http://dx.doi.org/10.1089/neu.2018.5660},
  doi          = {10.1089/neu.2018.5660},
  volume       = {35},
  year         = {2018},
}