PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia

Abstract Insulin-like growth factor-I (IGF-I) is involved in the maturation and maintenance of neurons, and impaired IGF-I signaling has been shown to play a role in various neurological diseases including stroke. The aim of the present study was to investigate the efficacy of an optimized IGF-I var...

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Autores principales:	Kim Parker, Antonio Berretta, Stefanie Saenger, Manaswini Sivaramakrishnan, Simon A. Shirley, Friedrich Metzger, Andrew N. Clarkson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9573be34d1cf477683505c56800f4a1c
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spelling	oai:doaj.org-article:9573be34d1cf477683505c56800f4a1c2021-12-02T12:30:52ZPEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia10.1038/s41598-017-00336-z2045-2322https://doaj.org/article/9573be34d1cf477683505c56800f4a1c2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00336-zhttps://doaj.org/toc/2045-2322Abstract Insulin-like growth factor-I (IGF-I) is involved in the maturation and maintenance of neurons, and impaired IGF-I signaling has been shown to play a role in various neurological diseases including stroke. The aim of the present study was to investigate the efficacy of an optimized IGF-I variant by adding a 40 kDa polyethylene glycol (PEG) chain to IGF-I to form PEG-IGF-I. We show that PEG-IGF-I has a slower clearance which allows for twice-weekly dosing to maintain steady-state serum levels in mice. Using a photothrombotic model of focal stroke, dosing from 3 hrs post-stroke dose-dependently (0.3–1 mg/kg) decreases the volume of infarction and improves motor behavioural function in both young 3-month and aged 22–24 month old mice. Further, PEG-IGF-I treatment increases GFAP expression when given early (3 hrs post-stroke), increases Synaptophysin expression and increases neurogenesis in young and aged. Finally, neurons (P5–6) cultured in vitro on reactive astrocytes in the presence of PEG-IGF-I showed an increase in neurite length, indicating that PEG-IGF-I can aid in sprouting of new connections. This data suggests a modulatory role of IGF-I in both protective and regenerative processes, and indicates that therapeutic approaches using PEG-IGF-I should be given early and where the endogenous regenerative potential is still high.Kim ParkerAntonio BerrettaStefanie SaengerManaswini SivaramakrishnanSimon A. ShirleyFriedrich MetzgerAndrew N. ClarksonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kim Parker Antonio Berretta Stefanie Saenger Manaswini Sivaramakrishnan Simon A. Shirley Friedrich Metzger Andrew N. Clarkson PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
description	Abstract Insulin-like growth factor-I (IGF-I) is involved in the maturation and maintenance of neurons, and impaired IGF-I signaling has been shown to play a role in various neurological diseases including stroke. The aim of the present study was to investigate the efficacy of an optimized IGF-I variant by adding a 40 kDa polyethylene glycol (PEG) chain to IGF-I to form PEG-IGF-I. We show that PEG-IGF-I has a slower clearance which allows for twice-weekly dosing to maintain steady-state serum levels in mice. Using a photothrombotic model of focal stroke, dosing from 3 hrs post-stroke dose-dependently (0.3–1 mg/kg) decreases the volume of infarction and improves motor behavioural function in both young 3-month and aged 22–24 month old mice. Further, PEG-IGF-I treatment increases GFAP expression when given early (3 hrs post-stroke), increases Synaptophysin expression and increases neurogenesis in young and aged. Finally, neurons (P5–6) cultured in vitro on reactive astrocytes in the presence of PEG-IGF-I showed an increase in neurite length, indicating that PEG-IGF-I can aid in sprouting of new connections. This data suggests a modulatory role of IGF-I in both protective and regenerative processes, and indicates that therapeutic approaches using PEG-IGF-I should be given early and where the endogenous regenerative potential is still high.
format	article
author	Kim Parker Antonio Berretta Stefanie Saenger Manaswini Sivaramakrishnan Simon A. Shirley Friedrich Metzger Andrew N. Clarkson
author_facet	Kim Parker Antonio Berretta Stefanie Saenger Manaswini Sivaramakrishnan Simon A. Shirley Friedrich Metzger Andrew N. Clarkson
author_sort	Kim Parker
title	PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
title_short	PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
title_full	PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
title_fullStr	PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
title_full_unstemmed	PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia
title_sort	pegylated insulin-like growth factor-i affords protection and facilitates recovery of lost functions post-focal ischemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9573be34d1cf477683505c56800f4a1c
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PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia

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