dc.contributor.author |
Svedin, P |
en |
dc.contributor.author |
Guan, Jian |
en |
dc.contributor.author |
Mathai, Sam |
en |
dc.contributor.author |
Zhang, R |
en |
dc.contributor.author |
Wang, X |
en |
dc.contributor.author |
Gustavsson, M |
en |
dc.contributor.author |
Hagberg, H |
en |
dc.contributor.author |
Mallard, EC |
en |
dc.date.accessioned |
2012-03-21T00:16:25Z |
en |
dc.date.accessioned |
2012-03-26T23:44:42Z |
en |
dc.date.issued |
2007 |
en |
dc.identifier.citation |
Developmental Neuroscience 29(4-5):393-402 01 Jan 2007 |
en |
dc.identifier.issn |
0378-5866 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/15504 |
en |
dc.description.abstract |
Glycine 2-methyl proline glutamate (G-2mPE) is a proline-modified analogue to the naturally existing N-terminal tripeptide glycine-proline-glutamate that is a cleaved product from insulin-like growth factor-1. G-2mPE is designed to be more enzymatically resistant than glycine-proline-glutamate and to increase its bioavailability. The current study has investigated the protective effects of G-2mPE following hypoxic-ischemic brain injury in the neonatal brain. On postnatal day 7, Wistar rats were exposed to hypoxia-ischemia (HI). HI was induced by unilateral ligation of the left carotid artery followed by hypoxia (7.7% O2, 36 degrees C) for 60 min. The drug treatment started 2 h after the insult, and the pups were given either 1.2 mg/kg (bolus), 1.2 mg/ml once a day for 7 days, or vehicle. The degree of brain damage was determined histochemically by thionin/acid fuchsin staining. G-2mPE's anti-inflammatory properties were investigated by IL-1beta, IL-6, and IL-18 ELISA, and effects on apoptosis by caspase 3 activity. Vascularization was determined immunohistochemically by the total length of isolectin-positive blood vessels. Effect on astrocytosis was also determined in the hippocampus. Animals treated with multiple doses of G-2mPE demonstrated reduced overall brain injury 7 days after HI, particularly in the hippocampus and thalamus compared to vehicle-treated rats. The expression of IL-6 was decreased in G-2mPE-treated animals compared to vehicle-treated pups, and both the capillary length and astrogliosis were increased in the drug-treated animals. There was no effect on caspase 3 activity. This study indicates that peripheral administration of G-2mPE, starting 2 h after a hypoxic-ischemic insult, reduces the degree of brain injury in the immature rat brain. The normalization of IL-6 levels and the promotion of both neovascularization and reactive astrocytosis may be potential mechanisms that underlie its protective effects. 2007 S. Karger AG, Basel |
en |
dc.publisher |
Karger |
en |
dc.relation.ispartofseries |
Developmental Neuroscience |
en |
dc.relation.replaces |
http://hdl.handle.net/2292/14769 |
en |
dc.relation.replaces |
2292/14769 |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0378-5866/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Delayed peripheral administration of a GPE analogue induces astrogliosis and angiogenesis and reduces inflammation and brain injury following hypoxia-ischemia in the neonatal rat. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1159/000105480 |
en |
pubs.issue |
4 |
en |
pubs.begin-page |
393 |
en |
pubs.volume |
29 |
en |
dc.rights.holder |
Copyright: Karger |
en |
dc.identifier.pmid |
17762207 |
en |
pubs.end-page |
402 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
69262 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
Physiology Division |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
17762207 |
en |