Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8273790 | Journal of the Neurological Sciences | 2016 | 9 Pages |
Abstract
Growth differentiation factor 11 (GDF11), as a rejuvenation factor in heterochronic parabiosis, can increase proliferation of primary brain capillary endothelial cells (ECs). However, the angiogenic role of GDF11 in ischemia-induced brain injury is still unclear. There are no previous reports on the spatiotemporal expression of GDF11 in cerebral ischemia/reperfusion (I/R) rats. Our recent work has strongly suggested that transcutaneous auricular vagus nerve stimulation (ta-VNS) reduces infarct size and induces angiogenesis in focal cerebral I/R rats. This study focused on expression of GDF11 and activin-like kinase 5 (ALK5) and the effects of ta-VNS in a rat cerebral I/R model. For ta-VNS, electrical stimulation of the left cavum concha (1Â h duration) using percutaneous needles was initiated 30Â min after induction of ischemia. Expression of GDF11 was analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, real-time polymerase chain reaction, and western blot 24Â h, 3Â d, and 7Â d after reperfusion. In addition, neurobehavioral function, EC proliferation, and expression of ALK5 in ECs in the peri-infarct cortex were measured. Results showed that levels of GDF11 were significantly elevated after cerebral I/R, both in plasma and the peri-infarct cerebral cortex. Interestingly, splenic GDF11 levels decreased after ischemia. ALK5 was expressed in ECs in the peri-infarct cerebral cortex where active vessel remodeling was noted. ta-VNS improved neurobehavioral recovery, upregulated cerebral GDF11 and downregulated splenic GDF11, indicating a brain-spleen communication during stroke. ta-VNS also increased expression of ALK5 in ECs and stimulated proliferation of ECs. These results suggest that, after cerebral ischemia, GDF11 redistributes and participates in angiogenesis as an angiogenic factor that acts at least in part through ALK5. GDF11/ALK5 may represent a new potential therapy target for stroke.
Keywords
activin-like kinase 5mNSSEPCsABPCVNsrCBFCCAALK5GAPDHGDF11MCAO/RLSDECAICATGF-βECsI/Rq-PCRenzyme linked immunosorbent assaymiddle cerebral artery occlusion/reperfusionischemia/reperfusiontransforming growth factor-βanalysis of varianceANOVAELISAMinleast significant differenceEndothelial progenitor cellsEndothelial cellsexternal carotid arteryinternal carotid arterycommon carotid arteryHeart rategrowth differentiation factor 11Arterial blood pressurequantitative real-time polymerase chain reactionglyceraldehyde 3-phosphate dehydrogenase
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Authors
Jingxi Ma, Lina Zhang, Guoqian He, Xiaodan Tan, Xinhao Jin, Changqing Li,