Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke

Estrid Thougaard; Pernille Vinther Nielsen; Amalie Forsberg; Victoria Phuong; Aitana Martínez Velasco; Agnieszka Wlodarczyk; Harald Wajant; Isabell Lang; Jens D. Mikkelsen; Bettina Hjelm Clausen; Roberta Brambilla; Kate Lykke Lambertsen

doi:10.1016/j.jneuroim.2023.578246

Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke

Estrid Thougaard, Pernille Vinther Nielsen, Amalie Forsberg, Victoria Phuong, Aitana Martínez Velasco, Agnieszka Wlodarczyk, Harald Wajant, Isabell Lang, Jens D. Mikkelsen, Bettina Hjelm Clausen, Roberta Brambilla, Kate Lykke Lambertsen^*

^*Corresponding author af dette arbejde

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Abstract

Ischemic stroke often leaves survivors with permanent disabilities and therapies aimed at limiting detrimental inflammation and improving functional outcome are still needed. Tumor necrosis factor (TNF) levels increase rapidly after ischemic stroke, and while signaling through TNF receptor 1 (TNFR1) is primarily detrimental, TNFR2 signaling mainly has protective functions. We therefore investigated how systemic stimulation of TNFR2 with the TNFR2 agonist NewSTAR2 affects ischemic stroke in mice. We found that NewSTAR2 treatment induced changes in peripheral immune cell numbers and transiently affected microglial numbers and neuroinflammation. However, this was not sufficient to improve long-term functional outcome after stroke in mice.

Originalsprog	Engelsk
Artikelnummer	578246
Tidsskrift	Journal of Neuroimmunology
Vol/bind	385
Antal sider	17
ISSN	0165-5728
DOI	https://doi.org/10.1016/j.jneuroim.2023.578246
Status	Udgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the Independent Research Fund Denmark ( 0134-00084B ), the Carlsberg Foundation ( CF21–0215 ), the Novo Nordic Foundation ( NNF22OC0079804 ), and the Danish Alzheimer Association's Research Prize in Basic Research to K.L.L.; by the A.P. Møller Foundation ( 20-L-0269 and L-2022-00268 ), Overlægerådets Forskningsfond at the Odense University Hospital ( 110-A4683 ), and the Faculty of Health Sciences at the University of Southern Denmark to E.T.; and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation ) (project number: 324392634 , grants: TRR 221 and WA 1025/31–3 ) to H.W.

Publisher Copyright:
© 2023 The Authors

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10.1016/j.jneuroim.2023.578246Licens: CC BY

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Citationsformater

Thougaard, E., Nielsen, P. V., Forsberg, A., Phuong, V., Velasco, A. M., Wlodarczyk, A., Wajant, H., Lang, I., Mikkelsen, J. D., Clausen, B. H., Brambilla, R., & Lambertsen, K. L. (2023). Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke. Journal of Neuroimmunology, 385, [578246]. https://doi.org/10.1016/j.jneuroim.2023.578246

Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke. / Thougaard, Estrid; Nielsen, Pernille Vinther; Forsberg, Amalie; Phuong, Victoria; Velasco, Aitana Martínez; Wlodarczyk, Agnieszka; Wajant, Harald; Lang, Isabell; Mikkelsen, Jens D.; Clausen, Bettina Hjelm; Brambilla, Roberta; Lambertsen, Kate Lykke.

I: Journal of Neuroimmunology, Bind 385, 578246, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Thougaard, E, Nielsen, PV, Forsberg, A, Phuong, V, Velasco, AM, Wlodarczyk, A, Wajant, H, Lang, I, Mikkelsen, JD, Clausen, BH, Brambilla, R & Lambertsen, KL 2023, 'Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke', Journal of Neuroimmunology, bind 385, 578246. https://doi.org/10.1016/j.jneuroim.2023.578246

Thougaard, Estrid ; Nielsen, Pernille Vinther ; Forsberg, Amalie ; Phuong, Victoria ; Velasco, Aitana Martínez ; Wlodarczyk, Agnieszka ; Wajant, Harald ; Lang, Isabell ; Mikkelsen, Jens D. ; Clausen, Bettina Hjelm ; Brambilla, Roberta ; Lambertsen, Kate Lykke. / Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke. I: Journal of Neuroimmunology. 2023 ; Bind 385.

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abstract = "Ischemic stroke often leaves survivors with permanent disabilities and therapies aimed at limiting detrimental inflammation and improving functional outcome are still needed. Tumor necrosis factor (TNF) levels increase rapidly after ischemic stroke, and while signaling through TNF receptor 1 (TNFR1) is primarily detrimental, TNFR2 signaling mainly has protective functions. We therefore investigated how systemic stimulation of TNFR2 with the TNFR2 agonist NewSTAR2 affects ischemic stroke in mice. We found that NewSTAR2 treatment induced changes in peripheral immune cell numbers and transiently affected microglial numbers and neuroinflammation. However, this was not sufficient to improve long-term functional outcome after stroke in mice.",

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AU - Thougaard, Estrid

AU - Nielsen, Pernille Vinther

AU - Forsberg, Amalie

AU - Phuong, Victoria

AU - Velasco, Aitana Martínez

AU - Wlodarczyk, Agnieszka

AU - Wajant, Harald

AU - Lang, Isabell

AU - Mikkelsen, Jens D.

AU - Clausen, Bettina Hjelm

AU - Brambilla, Roberta

AU - Lambertsen, Kate Lykke

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N2 - Ischemic stroke often leaves survivors with permanent disabilities and therapies aimed at limiting detrimental inflammation and improving functional outcome are still needed. Tumor necrosis factor (TNF) levels increase rapidly after ischemic stroke, and while signaling through TNF receptor 1 (TNFR1) is primarily detrimental, TNFR2 signaling mainly has protective functions. We therefore investigated how systemic stimulation of TNFR2 with the TNFR2 agonist NewSTAR2 affects ischemic stroke in mice. We found that NewSTAR2 treatment induced changes in peripheral immune cell numbers and transiently affected microglial numbers and neuroinflammation. However, this was not sufficient to improve long-term functional outcome after stroke in mice.

AB - Ischemic stroke often leaves survivors with permanent disabilities and therapies aimed at limiting detrimental inflammation and improving functional outcome are still needed. Tumor necrosis factor (TNF) levels increase rapidly after ischemic stroke, and while signaling through TNF receptor 1 (TNFR1) is primarily detrimental, TNFR2 signaling mainly has protective functions. We therefore investigated how systemic stimulation of TNFR2 with the TNFR2 agonist NewSTAR2 affects ischemic stroke in mice. We found that NewSTAR2 treatment induced changes in peripheral immune cell numbers and transiently affected microglial numbers and neuroinflammation. However, this was not sufficient to improve long-term functional outcome after stroke in mice.

KW - Cytokines

KW - Ischemic stroke

KW - Microglia

KW - Neuroinflammation

KW - Peripheral immune cells

KW - TNFR2 agonist

U2 - 10.1016/j.jneuroim.2023.578246

DO - 10.1016/j.jneuroim.2023.578246

M3 - Journal article

C2 - 37988839

AN - SCOPUS:85177485223

VL - 385

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

M1 - 578246

ER -