Cutaneous burn injury induces neuroinflammation and reactive astrocyte activation in the hippocampus of aged mice.
Advanced age
Brain
Chemokine
Cytokine
Dentate gyrus
Inflamm-aging
Traumatic injury
Journal
Experimental gerontology
ISSN: 1873-6815
Titre abrégé: Exp Gerontol
Pays: England
ID NLM: 0047061
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
10
07
2022
revised:
29
09
2022
accepted:
30
09
2022
pubmed:
9
10
2022
medline:
2
11
2022
entrez:
8
10
2022
Statut:
ppublish
Résumé
By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro-inflammatory activation of astrocytes within the hippocampus (HPC) after burn injury. Reduced levels of phosphorylated cyclic-AMP response binding element (pCREB), caused by elevated systemic pro-inflammatory cytokines, could lead to cognitive decline and memory impairment. To examine the effects of remote injury on neuroinflammation in advanced age, young and aged mice were subjected to a 15 % total body surface area scald burn or sham injury, and euthanized after 24 h. Expression of ccl2 and tnfa were measured by qPCR in the whole brain and HPC. Astrocyte activation was measured by immunofluorescence within the HPC. pCREB was measured by immunohistochemistry in the dentate gyrus. We saw an 80-fold increase in ccl2 and a 30-fold elevation in tnfa after injury in the whole brain of aged mice compared to young groups and aged sham mice (p < 0.05 and p < 0.05, respectively). Additionally, there was a 30-fold increase in ccl2 within isolated HPC of aged injured mice when compared to sham injured animals (p < 0.05). When investigating specific HPC regions, immunofluorescence staining showed a >20 % rise in glial fibrillary acidic protein (GFAP) positive astrocytes within the cornu ammonis 3 (CA3) of aged injured mice when compared to all other groups (p < 0.05). Lastly, we observed a >20 % decrease in pCREB staining by immunohistochemistry in the dentate gyrus of aged mice compared to young regardless of injury (p < 0.05). These novel data suggest that remote injury in aged, but not young, mice is associated with neuroinflammation and astrocyte activation within the HPC. These factors, paired with an age related reduction in pCREB, could help explain the increased cognitive decline seen in burn patients of advanced age. To our knowledge, we are the first group to examine the impact of advanced age combined with burn injury on inflammation and astrocyte activation within the brain.
Sections du résumé
BACKGROUND
By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro-inflammatory activation of astrocytes within the hippocampus (HPC) after burn injury. Reduced levels of phosphorylated cyclic-AMP response binding element (pCREB), caused by elevated systemic pro-inflammatory cytokines, could lead to cognitive decline and memory impairment.
METHODS
To examine the effects of remote injury on neuroinflammation in advanced age, young and aged mice were subjected to a 15 % total body surface area scald burn or sham injury, and euthanized after 24 h. Expression of ccl2 and tnfa were measured by qPCR in the whole brain and HPC. Astrocyte activation was measured by immunofluorescence within the HPC. pCREB was measured by immunohistochemistry in the dentate gyrus.
RESULTS
We saw an 80-fold increase in ccl2 and a 30-fold elevation in tnfa after injury in the whole brain of aged mice compared to young groups and aged sham mice (p < 0.05 and p < 0.05, respectively). Additionally, there was a 30-fold increase in ccl2 within isolated HPC of aged injured mice when compared to sham injured animals (p < 0.05). When investigating specific HPC regions, immunofluorescence staining showed a >20 % rise in glial fibrillary acidic protein (GFAP) positive astrocytes within the cornu ammonis 3 (CA3) of aged injured mice when compared to all other groups (p < 0.05). Lastly, we observed a >20 % decrease in pCREB staining by immunohistochemistry in the dentate gyrus of aged mice compared to young regardless of injury (p < 0.05).
CONCLUSIONS
These novel data suggest that remote injury in aged, but not young, mice is associated with neuroinflammation and astrocyte activation within the HPC. These factors, paired with an age related reduction in pCREB, could help explain the increased cognitive decline seen in burn patients of advanced age. To our knowledge, we are the first group to examine the impact of advanced age combined with burn injury on inflammation and astrocyte activation within the brain.
Identifiants
pubmed: 36208823
pii: S0531-5565(22)00283-2
doi: 10.1016/j.exger.2022.111975
pmc: PMC10246470
mid: NIHMS1901646
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
111975Subventions
Organisme : NIGMS NIH HHS
ID : K08 GM134185
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018859
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131831
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG000279
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.
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