Exendin-4 Reduces Ischemic Brain Injury in Normal and Aged Type 2 Diabetic Mice and Promotes Microglial M2 Polarization

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: onr:"swepub:oai:gup.ub.gu.se/202340" > Exendin-4 Reduces I...

1 of 1
Previous record
Next record
To hitlist

Details
MARC

Darsalia, V.Karolinska Institutet (author)

Exendin-4 Reduces Ischemic Brain Injury in Normal and Aged Type 2 Diabetic Mice and Promotes Microglial M2 Polarization

Article/chapterEnglish2014

Publisher, publication year, extent ...

2014-08-07
Public Library of Science (PLoS),2014

Numbers

LIBRIS-ID:oai:gup.ub.gu.se/202340
https://gup.ub.gu.se/publication/202340URI
https://doi.org/10.1371/journal.pone.0103114DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:129551106URI

Supplementary language notes

Language:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Exendin-4 is a glucagon-like receptor 1 agonist clinically used against type 2 diabetes that has also shown neuroprotective effects in experimental stroke models. However, while the neuroprotective efficacy of Exendin-4 has been thoroughly investigated if the pharmacological treatment starts before stroke, the therapeutic potential of the Exendin-4 if the treatment starts acutely after stroke has not been clearly determined. Further, a comparison of the neuroprotective efficacy in normal and aged diabetic mice has not been performed. Finally, the cellular mechanisms behind the efficacy of Exendin-4 have been only partially studied. The main objective of this study was to determine the neuroprotective efficacy of Exendin4 in normal and aged type 2 diabetic mice if the treatment started after stroke in a clinically relevant setting. Furthermore we characterized the Exendin-4 effects on stroke-induced neuroinflammation. Two-month-old healthy and 14-month-old type 2 diabetic/obese mice were subjected to middle cerebral artery occlusion. 5 or 50 mg/kg Exendin-4 was administered intraperitoneally at 1.5, 3 or 4.5 hours thereafter. The treatment was continued (0.2 mg/kg/day) for 1 week. The neuroprotective efficacy was assessed by stroke volume measurement and stereological counting of NeuN-positive neurons. Neuroinflammation was determined by gene expression analysis of M1/M2 microglia subtypes and proinflammatory cytokines. We show neuroprotective efficacy of 50 mg/kg Exendin-4 at 1.5 and 3 hours after stroke in both young healthy and aged diabetic/obese mice. The 5 mu g/kg dose was neuroprotective at 1.5 hour only. Proinflammatory markers and M1 phenotype were not impacted by Exendin-4 treatment while M2 markers were significantly up regulated. Our results support the use of Exendin-4 to reduce stroke-damage in the prehospital/early hospitalization setting irrespectively of age/diabetes. The results indicate the polarization of microglia/macrophages towards the M2 reparative phenotype as a potential mechanism of neuroprotection.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
GLUCAGON-LIKE PEPTIDE-1
TISSUE-PLASMINOGEN ACTIVATOR
FOCAL
CEREBRAL-ISCHEMIA
RECEPTOR STIMULATION
STROKE SEVERITY
NEUROPROTECTION
THROMBOLYSIS
REPERFUSION
INFARCTION
MECHANISM

Added entries (persons, corporate bodies, meetings, titles ...)

Hua, SansanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology (author)
Larsson, M.Karolinska Institutet (author)
Mallard, Carina,1963Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xmallc (author)
Nathanson, D.Karolinska Institutet (author)
Nystrom, T.Karolinska Institutet (author)
Sjoholm, A. (author)
Johansson, Maria E,1977Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjmarw (author)
Patrone, C.Karolinska Institutet (author)
Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för fysiologi (creator_code:org_t)

Related titles

In:Plos One: Public Library of Science (PLoS)9:81932-6203

Internet link

Find in a library

Plos One (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Darsalia, V.; Hua, Sansan; Larsson, M.; Mallard, Carina, ...; Nathanson, D.; Nystrom, T.; show more...; Sjoholm, A.; Johansson, Maria ...; Patrone, C.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

Articles in the publication: Plos One

By the university: University of Gothenburg; Karolinska Institutet

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se