Growth differentiation factor 11 improves neurobehavioral recovery and stimulates angiogenesis in rats subjected to cerebral ischemia/reperfusion
Autor: | Chibo Ai, Lan Wen, Gongwei Jia, Lina Zhang, Xinhao Jin, Tengfei Niu, Jingxi Ma, Keming Zhang, Changqing Li, Qinbin Zhang |
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Rok vydání: | 2018 |
Předmět: |
Brain Infarction
Male 0301 basic medicine Angiogenesis Receptor Transforming Growth Factor-beta Type I Ischemia Pharmacology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Antigens CD In vivo Animals Medicine Stroke Neurologic Examination Analysis of Variance Dose-Response Relationship Drug Neovascularization Pathologic business.industry General Neuroscience Growth differentiation factor Infarction Middle Cerebral Artery medicine.disease Rats Growth Differentiation Factors Ki-67 Antigen 030104 developmental biology medicine.anatomical_structure Cerebral cortex Reperfusion Psychomotor Disorders Signal transduction business Psychomotor disorder 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Brain Research Bulletin. 139:38-47 |
ISSN: | 0361-9230 |
Popis: | The recent suggestion that growth differentiation factor 11 (GDF11) acts as a rejuvenation factor has remained controversial. However, in addition to its role in aging, the relationship between GDF11 and cerebral ischemia is still an important area that needs more investigation. Here we examined effects of GDF11 on angiogenesis and recovery of neurological function in a rat model of stroke. Exogenous recombinant GDF11 (rGDF11) at different doses were directly injected into the tail vein in rats subjected to cerebral ischemia/reperfusion (I/R). Neurobehavioral tests were performed, the proliferation of endothelial cells (ECs) and GDF11 downstream signal activin-like kinase 5 (ALK5) were assessed, and functional microvessels were measured. Results showed that rGDF11 at a dosage of 0.1 mg/kg/day could effectively activate cerebral angiogenesis in vivo. In addition, rGDF11 improved the modified neurological severity scores and the adhesive removal somatosensory test, promoted proliferation of ECs, induced ALK5 and increased vascular surface area and the number of vascular branch points in the peri-infarct cerebral cortex after cerebral I/R. These effects were suppressed by blocking ALK5. Our novel findings shed new light on the role of GDF11. Our results strongly suggest that GDF11 improves neurofunctional recovery from cerebral I/R injury and that this effect is mediated partly through its proangiogenic effect in the peri-infarct cerebral cortex, which is associated with ALK5. Thus, GDF11/ALK5 may represent new therapeutic targets for aiding recovery from stroke. |
Databáze: | OpenAIRE |
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