Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model

Wang, Chao ; Iashchishyn, Igor A ; Kara, John ; Foderà, Vito ; Vetri, Valeria ; Sancataldo, Giuseppe ; Marklund, Niklas LU orcid and Morozova-Roche, Ludmilla A (2019) In Neuroscience Letters 699. p.199-205
Abstract

Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer's and Parkinson's. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer's as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post-TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain... (More)

Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer's and Parkinson's. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer's as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post-TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain tissues during post-TBI recovery. By using sequential immunohistochemistry we have shown that S100A9 was produced by both neuronal and microglial cells. However, Aβ peptide deposits characteristic for Alzheimer's disease were not detected in any post-TBI animals. On the first and third post-TBI days S100A9 was found to aggregate intracellularly into amyloid oligomers, similar to what was previously observed in human TBI tissues. Complementary, by using Rayleigh scatting, intrinsic fluorescence and atomic force microscopy we demonstrated that in vitro S100A9 self-assembles into amyloid oligomers within minutes. Its amyloid aggregation is highly dependent on changes of environmental conditions such as variation of calcium levels, pH, temperature and reduction/oxidation, which might be relevant to perturbation of cellular and tissues homeostasis under TBI. Present results demonstrate that S100A9 induction mechanisms in TBI are similar in mice and humans, emphasizing that S100A9 is an important marker of brain injury and therefore can be a potential therapeutic target.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuroscience Letters
volume
699
pages
199 - 205
publisher
Elsevier
external identifiers
  • scopus:85061554746
  • pmid:30753908
ISSN
0304-3940
DOI
10.1016/j.neulet.2019.02.012
language
English
LU publication?
no
id
507d072c-9419-4c0f-8760-5e15c3cbd6f6
date added to LUP
2019-03-06 20:58:09
date last changed
2024-07-23 10:38:08
@article{507d072c-9419-4c0f-8760-5e15c3cbd6f6,
  abstract     = {{<p>Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer's and Parkinson's. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer's as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post-TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain tissues during post-TBI recovery. By using sequential immunohistochemistry we have shown that S100A9 was produced by both neuronal and microglial cells. However, Aβ peptide deposits characteristic for Alzheimer's disease were not detected in any post-TBI animals. On the first and third post-TBI days S100A9 was found to aggregate intracellularly into amyloid oligomers, similar to what was previously observed in human TBI tissues. Complementary, by using Rayleigh scatting, intrinsic fluorescence and atomic force microscopy we demonstrated that in vitro S100A9 self-assembles into amyloid oligomers within minutes. Its amyloid aggregation is highly dependent on changes of environmental conditions such as variation of calcium levels, pH, temperature and reduction/oxidation, which might be relevant to perturbation of cellular and tissues homeostasis under TBI. Present results demonstrate that S100A9 induction mechanisms in TBI are similar in mice and humans, emphasizing that S100A9 is an important marker of brain injury and therefore can be a potential therapeutic target.</p>}},
  author       = {{Wang, Chao and Iashchishyn, Igor A and Kara, John and Foderà, Vito and Vetri, Valeria and Sancataldo, Giuseppe and Marklund, Niklas and Morozova-Roche, Ludmilla A}},
  issn         = {{0304-3940}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{199--205}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience Letters}},
  title        = {{Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model}},
  url          = {{http://dx.doi.org/10.1016/j.neulet.2019.02.012}},
  doi          = {{10.1016/j.neulet.2019.02.012}},
  volume       = {{699}},
  year         = {{2019}},
}