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
(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.
(Less)
- author
- Ozen, Ilknur
LU
; Ruscher, Karsten
LU
; Nilsson, Robert
; Flygt, Johanna
; Clausen, Fredrik
and Marklund, Niklas
LU
- organization
- publishing date
- 2020
- 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
- 2024-06-27 06:37:57
@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}},
}