The neuroprotective and neurorestorative effects of growth differentiation factor 11 in cerebral ischemic injury

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, regulates various biological processes in mammals. The effect of GDF11 in brain injury has not been fully elucidated. Our aim was to investigate the effects of GDF11 in cerebral ischemic injury. The expression level of GDF11 increased significantly in the peri-infarct cerebral cortex. Next, the effect of the intracerebroventricular injection of a GDF11 overexpression lentivirus or rGDF11 was investigated in middle cerebral artery occlusion (MCAO) rats. The preventative effects of the GDF11 overexpression virus on stroke were observed. The delivery of the lentivirus into rats before MCAO significantly reduced the infarct volume and the percentage of apoptotic cells and improved motor function in MCAO rats. Furthermore, it elevated the expression of p-Smad2/3 and promoted neurogenesis and angiogenesis in the ipsilateral SVZ during ischemic injury. More importantly, the therapeutic effects of rGDF11 on stroke were subsequently explored. The results in MCAO rats treated with rGDF11 were found similar to that in those treated with the GDF11 overexpression lentivirus. Together, these findings indicate that GDF11 has neuroprotective and neurorestorative effects in cerebral ischemic injury and provide new insights into the function and mechanism of GDF11 in stroke models.