RGD Reference Report - Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat. - Rat Genome Database

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Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.

Authors: Yan, Han  Mitschelen, Matthew  Toth, Peter  Ashpole, Nicole M  Farley, Julie A  Hodges, Erik L  Warrington, Junie P  Han, Song  Fung, Kar-Ming  Csiszar, Anna  Ungvari, Zoltan  Sonntag, William E 
Citation: Yan H, etal., J Gerontol A Biol Sci Med Sci. 2014 Nov;69(11):1353-62. doi: 10.1093/gerona/glu118. Epub 2014 Aug 6.
RGD ID: 12904924
Pubmed: PMID:25098324   (View Abstract at PubMed)
PMCID: PMC4271094   (View Article at PubMed Central)
DOI: DOI:10.1093/gerona/glu118   (Journal Full-text)

Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia severityISOIgf1 (Rattus norvegicus)12904924; 12904924protein:decreased expression:serum (rat)RGD 
transient cerebral ischemia severityIEP 12904924protein:decreased expression:serum (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)


Additional Information