Abstract
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<0.05). GDF11 supplementation reduced mortality and improved sensorimotor deficits after stroke. Treatment also reduced brain atrophy and gliosis, increased angiogenesis, improved white matter integrity, and reduced inflammation after stroke. GDF11 may have a role in brain repair after ischemic injury.
Highlights
With aging, many changes in structural and biological processes occur, and in part can be explained by alterations in circulating systemic factors
A slight increase in the brain pSmad2 and pSmad3 expression was seen in the sham mice treated with recombinant growth differentiation factor-11 (rGDF11) compared to sham vehicle, this did not reach statistical difference
No difference between sham rGDF11 and middle cerebral artery occlusion (MCAo) rGDF11 treated mice was seen in brain pSmad2 and pSmad3 expression
Summary
Many changes in structural and biological processes occur, and in part can be explained by alterations in circulating systemic factors. Other studies have found that GDF11 may inhibit skeletal muscle regeneration and had no effect on cardiac hypertrophy [6, 8], leading to considerable controversy regarding the utility of GDF11 supplementation as a therapeutic strategy. Many of these studies used different routes of administration and dosing [2, 6, 10]
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