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Interleukin-1 beta neutralization attenuates traumatic brain injury-induced microglia activation and neuronal changes in the globus pallidus

Ozen, Ilknur LU ; Ruscher, Karsten LU ; Nilsson, Robert ; Flygt, Johanna ; Clausen, Fredrik and Marklund, Niklas LU orcid (2020) In International Journal of Molecular Sciences 21(2).
Abstract

Traumatic brain injury (TBI) increases the risk of delayed neurodegenerative processes, including Parkinson’s disease (PD). Interleukin-1beta (IL-1β), a key pro-inflammatory cytokine, may promote secondary injury development after TBI. Conversely, neutralizing IL-1β was found to improve functional recovery following experimental TBI. However, the mechanisms underlying the behavioral improvements observed by IL-1β neutralization are still poorly understood. The present study investigated the role of IL-1β on the microglia response and neuronal changes in the globus pallidus in response to diffuse TBI. Mice were subjected to sham injury or the central fluid percussion injury (cFPI) (a model of traumatic axonal injury), and were randomly... (More)

Traumatic brain injury (TBI) increases the risk of delayed neurodegenerative processes, including Parkinson’s disease (PD). Interleukin-1beta (IL-1β), a key pro-inflammatory cytokine, may promote secondary injury development after TBI. Conversely, neutralizing IL-1β was found to improve functional recovery following experimental TBI. However, the mechanisms underlying the behavioral improvements observed by IL-1β neutralization are still poorly understood. The present study investigated the role of IL-1β on the microglia response and neuronal changes in the globus pallidus in response to diffuse TBI. Mice were subjected to sham injury or the central fluid percussion injury (cFPI) (a model of traumatic axonal injury), and were randomly administered an IL-1β neutralizing or a control antibody at 30 min post-injury. The animals were analyzed at 2, 7, or 14 days post-injury. When compared to controls, mice subjected to cFPI TBI had increased microglia activation and dopaminergic innervation in the globus pallidus, and a decreased number of parvalbumin (PV) positive interneurons in the globus pallidus. Neutralization of IL-1β attenuated the microglia activation, prevented the loss of PV+ interneurons and normalized dopaminergic fiber density in the globus pallidus of brain-injured animals. These findings argue for an important role for neuro-inflammation in the PD-like pathology observed in TBI.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Axonal injury, Globus pallidus, Inflammation, Interleukin-1β, Parkinson’s disease, Traumatic brain injury
in
International Journal of Molecular Sciences
volume
21
issue
2
article number
387
publisher
MDPI AG
external identifiers
  • scopus:85077902035
  • pmid:31936248
ISSN
1661-6596
DOI
10.3390/ijms21020387
language
English
LU publication?
yes
id
b8f8c7a6-f85b-41f4-9858-e29ea8539b6b
date added to LUP
2021-01-13 14:10:45
date last changed
2024-06-13 05:08:34
@article{b8f8c7a6-f85b-41f4-9858-e29ea8539b6b,
  abstract     = {{<p>Traumatic brain injury (TBI) increases the risk of delayed neurodegenerative processes, including Parkinson’s disease (PD). Interleukin-1beta (IL-1β), a key pro-inflammatory cytokine, may promote secondary injury development after TBI. Conversely, neutralizing IL-1β was found to improve functional recovery following experimental TBI. However, the mechanisms underlying the behavioral improvements observed by IL-1β neutralization are still poorly understood. The present study investigated the role of IL-1β on the microglia response and neuronal changes in the globus pallidus in response to diffuse TBI. Mice were subjected to sham injury or the central fluid percussion injury (cFPI) (a model of traumatic axonal injury), and were randomly administered an IL-1β neutralizing or a control antibody at 30 min post-injury. The animals were analyzed at 2, 7, or 14 days post-injury. When compared to controls, mice subjected to cFPI TBI had increased microglia activation and dopaminergic innervation in the globus pallidus, and a decreased number of parvalbumin (PV) positive interneurons in the globus pallidus. Neutralization of IL-1β attenuated the microglia activation, prevented the loss of PV+ interneurons and normalized dopaminergic fiber density in the globus pallidus of brain-injured animals. These findings argue for an important role for neuro-inflammation in the PD-like pathology observed in TBI.</p>}},
  author       = {{Ozen, Ilknur and Ruscher, Karsten and Nilsson, Robert and Flygt, Johanna and Clausen, Fredrik and Marklund, Niklas}},
  issn         = {{1661-6596}},
  keywords     = {{Axonal injury; Globus pallidus; Inflammation; Interleukin-1β; Parkinson’s disease; Traumatic brain injury}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Interleukin-1 beta neutralization attenuates traumatic brain injury-induced microglia activation and neuronal changes in the globus pallidus}},
  url          = {{http://dx.doi.org/10.3390/ijms21020387}},
  doi          = {{10.3390/ijms21020387}},
  volume       = {{21}},
  year         = {{2020}},
}