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Delayed peripheral ...
Delayed peripheral administration of a GPE analogue induces astrogliosis and angiogenesis and reduces inflammation and brain injury following hypoxia-ischemia in the neonatal rat.
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- Svedin, Pernilla, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Guan, Jian (författare)
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Mathai, Sam (författare)
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Zhang, Rong (författare)
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- Wang, Xiaoyang, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Gustavsson, Malin (författare)
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- Hagberg, Henrik, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Mallard, Carina, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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(creator_code:org_t)
- 2007-08-31
- 2007
- Engelska.
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Ingår i: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 29:4-5, s. 393-402
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Animals
- Animals
- Newborn
- Apoptosis
- drug effects
- physiology
- Astrocytes
- drug effects
- physiology
- Birth Injuries
- drug therapy
- pathology
- physiopathology
- Brain
- blood supply
- drug effects
- physiopathology
- Caspase 3
- drug effects
- metabolism
- Cerebral Arteries
- drug effects
- growth & development
- Disease Models
- Animal
- Drug Administration Schedule
- Encephalitis
- drug therapy
- pathology
- physiopathology
- Gliosis
- drug therapy
- pathology
- physiopathology
- Hypoxia-Ischemia
- Brain
- drug therapy
- pathology
- physiopathology
- Interleukins
- metabolism
- Neovascularization
- Physiologic
- drug effects
- physiology
- Nerve Degeneration
- drug therapy
- pathology
- physiopathology
- Neuroprotective Agents
- pharmacology
- therapeutic use
- Oligopeptides
- pharmacology
- therapeutic use
- Rats
- Rats
- Wistar
- Time Factors
- Treatment Outcome
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Svedin, Pernilla ...
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Guan, Jian
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Mathai, Sam
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Zhang, Rong
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Wang, Xiaoyang, ...
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Gustavsson, Mali ...
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Hagberg, Henrik, ...
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Mallard, Carina, ...
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Developmental ne ...
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Göteborgs universitet