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

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Article number	578246
Journal	Journal of Neuroimmunology
Volume	385
ISSN	0165-5728
DOIs	https://doi.org/10.1016/j.jneuroim.2023.578246
Publication status	Published - 17. Nov 2023

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10.1016/j.jneuroim.2023.578246Licence: CC BY

Open Access VersionFinal published version, 12.2 MBLicence: CC BY

1 Ph.D. thesis

TNF signaling properties in acute and chronic inflammatory conditions
Pedersen, E. T., 14. Dec 2023, Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet. 226 p.
Research output: Thesis › Ph.D. thesis

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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, Article 578246. https://doi.org/10.1016/j.jneuroim.2023.578246

@article{626148d476dc4d74ba5631e8dcee0d35,

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

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.",

author = "Estrid Thougaard and Nielsen, {Pernille Vinther} and Amalie Forsberg and Victoria Phuong and Velasco, {Aitana Mart{\'i}nez} and Agnieszka Wlodarczyk and Harald Wajant and Isabell Lang and Mikkelsen, {Jens D} and Clausen, {Bettina Hjelm} and Roberta Brambilla and Lambertsen, {Kate Lykke}",

year = "2023",

month = nov,

day = "17",

doi = "10.1016/j.jneuroim.2023.578246",

language = "English",

volume = "385",

journal = "Journal of Neuroimmunology",

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publisher = "Elsevier",

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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, vol. 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 et al.
In: Journal of Neuroimmunology, Vol. 385, 578246, 17.11.2023.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke

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

PY - 2023/11/17

Y1 - 2023/11/17

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.

U2 - 10.1016/j.jneuroim.2023.578246

DO - 10.1016/j.jneuroim.2023.578246

M3 - Journal article

C2 - 37988839

SN - 0165-5728

VL - 385

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

M1 - 578246

ER -

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

Abstract

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TNF signaling properties in acute and chronic inflammatory conditions

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