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

J Gerontol A Biol Sci Med Sci. 2014 Nov;69(11):1353-62. doi: 10.1093/gerona/glu118. Epub 2014 Aug 6.

Abstract

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.

Keywords: Cerebral ischemia; Endothelin-1.; Insulin-like growth factor-1; Vascular aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Aging / physiology*
  • Animals
  • Astrocytes / pathology
  • Astrocytes / physiology
  • Brain Edema / etiology
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Brain Ischemia / etiology*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Cerebral Infarction / etiology
  • Cerebral Infarction / pathology
  • Cerebral Infarction / physiopathology
  • Disease Models, Animal
  • Dwarfism / genetics
  • Dwarfism / pathology
  • Dwarfism / physiopathology
  • Endothelin-1 / physiology*
  • Female
  • Growth Hormone / deficiency*
  • Growth Hormone / physiology
  • Insulin-Like Growth Factor I / deficiency*
  • Insulin-Like Growth Factor I / physiology
  • Male
  • Rats
  • Rats, Inbred Lew
  • Rats, Mutant Strains

Substances

  • Endothelin-1
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I
  • Growth Hormone