Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice

Growth differentiation factor (GDF) 11 levels decline with aging. The age-related loss of GDF 11 has been implicated in the pathogenesis of a variety of age-related diseases. GDF11 supplementation reversed cardiac hypertrophy, bone loss, and pulmonary dysfunction in old mice, suggesting that GDF11 h...

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Published in:Aging (Albany, NY.) NY.), 2020-05, Vol.12 (9), p.8049-8066
Main Authors: Hudobenko, Jacob, Ganesh, Bhanu Priya, Jiang, Jianjun, Mohan, Eric C, Lee, Songmi, Sheth, Sunil, Morales, Diego, Zhu, Liang, Kofler, Julia K, Pautler, Robia G, McCullough, Louise D, Chauhan, Anjali
Format: Article
Language:English
Subjects:
Aging
Animals
Blotting, Western
Bone Morphogenetic Proteins - pharmacokinetics
Brain - drug effects
Brain - metabolism
Dietary Supplements
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Growth Differentiation Factors - pharmacokinetics
Ischemic Stroke - diagnosis
Ischemic Stroke - drug therapy
Ischemic Stroke - mortality
Male
Mice
Recovery of Function - drug effects
Research Paper
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Summary:Growth differentiation factor (GDF) 11 levels decline with aging. The age-related loss of GDF 11 has been implicated in the pathogenesis of a variety of age-related diseases. GDF11 supplementation reversed cardiac hypertrophy, bone loss, and pulmonary dysfunction in old mice, suggesting that GDF11 has a rejuvenating effect. Less is known about the potential of GDF11 to improve recovery after an acute injury, such as stroke, in aged mice. GDF11/8 levels were assessed in young and aged male mice and in postmortem human brain samples. Aged mice were subjected to a transient middle cerebral artery occlusion (MCAo). Five days after MCAo, mice received and bromodeoxyuridine / 5-Bromo-2'-deoxyuridine (BrdU) and either recombinant GDF11 or vehicle for five days and were assessed for recovery for one month following stroke. MRI was used to determine cerebrospinal fluid (CSF) volume, corpus callosum (CC) area, and brain atrophy at 30 days post-stroke. Immunohistochemistry was used to assess gliosis, neurogenesis, angiogenesis and synaptic density. Lower GDF11/8 levels were found with age in both mice and humans (p
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.103122