Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord.
Neutrophils
Spinal cord injury
Spleen
Sympathetic fibers
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
23 Sep 2020
23 Sep 2020
Historique:
received:
14
04
2020
accepted:
26
08
2020
entrez:
24
9
2020
pubmed:
25
9
2020
medline:
30
7
2021
Statut:
epublish
Résumé
Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord. We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury. We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils' population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury. Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.
Sections du résumé
BACKGROUND
BACKGROUND
Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord.
METHODS
METHODS
We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury.
RESULTS
RESULTS
We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils' population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury.
CONCLUSION
CONCLUSIONS
Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.
Identifiants
pubmed: 32967684
doi: 10.1186/s12974-020-01945-8
pii: 10.1186/s12974-020-01945-8
pmc: PMC7513542
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
282Subventions
Organisme : Santa Casa da Misericórdia de Lisboa
ID : MC-04/17
Organisme : Fundação para a Ciência e a Tecnologia
ID : CEECIND/01902/2017
Organisme : Fundação para a Ciência e a Tecnologia
ID : SFRH/BD/112494/2015
Organisme : Fundação para a Ciência e a Tecnologia
ID : SFRH/BD/145860/2019
Organisme : Fundação para a Ciência e a Tecnologia
ID : PD/BDE/127836/2016
Organisme : Fundação para a Ciência e a Tecnologia
ID : CEECIND/03887/2017
Organisme : Fundação para a Ciência e a Tecnologia
ID : SFRH/BD/136952/2018
Organisme : Fundação para a Ciência e a Tecnologia
ID : PD/BD/127820/2016
Organisme : Fundação para a Ciência e a Tecnologia
ID : CEECIND/04794/2007
Organisme : Fundação para a Ciência e a Tecnologia
ID : PTDC/DTP-FTO/5109/2014
Organisme : Fundação para a Ciência e a Tecnologia
ID : POCI-01-0145-FEDER-007038
Organisme : Fundação para a Ciência e a Tecnologia
ID : NORTE-01-0145-FEDER-029968
Organisme : Fundação para a Ciência e a Tecnologia
ID : NORTE-01-0145-FEDER-000013
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