Transcutaneous auricular vagus nerve stimulation regulates expression of growth differentiation factor 11 and activin-like kinase 5 in cerebral ischemia/reperfusion rats

Autor: Xiao-dan Tan, Lina Zhang, Guo-qian He, Xinhao Jin, Changqing Li, Jingxi Ma
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Vagus Nerve Stimulation
Angiogenesis
medicine.medical_treatment
Receptor
Transforming Growth Factor-beta Type I
Ischemia
Stimulation
Protein Serine-Threonine Kinases
Severity of Illness Index
Functional Laterality
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Antigens
CD
Cortex (anatomy)
Internal medicine
medicine
Animals
Stroke
Cerebral Cortex
Afferent Pathways
business.industry
Infarction
Middle Cerebral Artery
Cerebral Infarction
medicine.disease
Rats
Growth Differentiation Factors
Disease Models
Animal
Ki-67 Antigen
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Neurology
Cerebral cortex
Cerebrovascular Circulation
Anesthesia
Reperfusion
GDF11
Neurology (clinical)
business
Receptors
Transforming Growth Factor beta
Psychomotor Performance
030217 neurology & neurosurgery
Vagus nerve stimulation
Zdroj: Journal of the Neurological Sciences. 369:27-35
ISSN: 0022-510X
Popis: 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 (1h duration) using percutaneous needles was initiated 30min after induction of ischemia. Expression of GDF11 was analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, real-time polymerase chain reaction, and western blot 24h, 3d, and 7d 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.
Databáze: OpenAIRE
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