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Protective Actions of Ghrelin Gene‐derived Peptides on the Brain after Ischemic Stroke
Author(s) -
Ku Jacqueline,
De Silva T Michael,
Barsby Tom,
Wong Connie,
Andrews Zane,
Sobey Christopher,
Miller Alyson
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.780.6
Subject(s) - ghrelin , neuroprotection , medicine , endocrinology , stroke (engine) , oxidative stress , nitric oxide , cerebral arteries , saline , receptor , mechanical engineering , engineering
The ghrelin gene‐derived peptides, acylated ghrelin (AG) and des‐acylated ghrelin (DAG), are best known as neuroendocrine hormones. However, recent evidence suggests they may have neuroprotective actions on the brain. Here, we examined their effect on stroke outcome after 0.5 h middle cerebral artery occlusion (MCAo). 24 h after MCAo, ghrelin ‐deficient ( Ghrl ‐/‐ ) mice had worse motor and neurological impairment vs. wild‐type (WT) mice ( P< 0.05, n=8‐10). Ghrl ‐/‐ mice also had larger infarct and edema volumes ( P< 0.05, n=10), and greater neuronal apoptosis ( P< 0.05, n=3). In a separate cohort of WT mice treated with vehicle (saline), AG, or DAG (1 mg/kg) at the time of reperfusion, DAG reduced infarct volumes vs. vehicle‐treated mice ( P< 0.05, n=10), whereas AG had no effect (n=8). We have recently revealed that DAG can modulate mechanisms (nitric oxide production and Nox2 oxidase activity) that are altered and contribute to cerebral artery dysfunction after stroke (Ku et al., 2014, Endocrinology ), whereas AG has no effect and its receptor (GHSR1a) is not expressed in cerebral vessels. Thus, DAG may target vascular mechanisms after stroke. Consistent with this concept, Nox2‐driven oxidative stress was exacerbated in cerebral arteries from ischemic hemispheres of Ghrl ‐/‐ mice ( P< 0.05 vs. WT, n=8‐9), and GHSR1a expression was negligible (n=3). Collectively, this study reveals protective actions of DAG on the brain and its vasculature after stroke. Our findings may prove to be all the more crucial when we consider that the production of DAG is suppressed in patients after stroke. Funded by the NHMRC.