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Activin A improves the neurological outcome after ischemic stroke in mice by promoting oligodendroglial ACVR1B-mediated white matter remyelination
- Source :
- Experimental neurology. 337
- Publication Year :
- 2020
-
Abstract
- Activin A plays important roles in ischemic injury and white matter remyelination, but its mechanisms are unclear. In this study, the adult male C57BL/6 J mice were used to establish the model of 1 h middle cerebral artery occlusion/reperfusion (MCAO/R) 1 d to 28 d-induced ischemic stroke in vivo. We found that the neurological outcome was positively correlated with the levels of myelin associated proteins (include MAG, CNPase, MOG and MBP, n = 6 per group) both in corpus callosum and internal capsule of mice with ischemic stroke. The dynamic changes of Luxol fast blue (LFB) staining intensity, oligodendrocyte (CC1+) and proliferated oligodendrocyte precursor (Ki67+/PDGFRα+) cell numbers indicated demyelination and spontaneous remyelination occurred in the corpus callosum of mice after 1 h MCAO/R 1 d-28 d (n = 6 per group). Activin receptor type I (ACVR1) inhibitor SB431542 aggregated neurological deficits, and reduced MAG, MOG and MBP protein levels of mice with ischemic stroke (n = 6 per group). Meanwhile, recombinant mouse (rm) Activin A enhanced the neurological function recovery, MAG, MOG and MBP protein levels of mice with 1 h MCAO/R 28 d. In addition, the injection of AAV-based ACVR1B shRNA with Olig2 promoter could reverse rmActivin A-induced the increases of CC1+ cell number, LFB intensity, MAG, MOG and MBP protein levels in the corpus callosum (n = 6 per group), and neurological function recovery (n = 10 per group) of mice with 1 h MCAO/R 28 d. These results suggested that Activin A improves the neurological outcome through promoting oligodendroglial ACVR1B-mediated white matter remyelination of mice with ischemic stroke, which may provide a potential therapeutic strategy for ischemic stroke.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Cell Count
Corpus callosum
Luxol fast blue stain
Corpus Callosum
White matter
03 medical and health sciences
Myelin
Mice
0302 clinical medicine
Developmental Neuroscience
Internal medicine
Medicine
Animals
Remyelination
ACVR1B
Myelin Sheath
Cell Proliferation
Ischemic Stroke
business.industry
Activin receptor
White Matter
Oligodendrocyte
Activins
Mice, Inbred C57BL
Oligodendroglia
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Neuroprotective Agents
Treatment Outcome
nervous system
Neurology
Reperfusion Injury
business
Activin Receptors, Type I
030217 neurology & neurosurgery
Demyelinating Diseases
Subjects
Details
- ISSN :
- 10902430
- Volume :
- 337
- Database :
- OpenAIRE
- Journal :
- Experimental neurology
- Accession number :
- edsair.doi.dedup.....e6635288a77932cd56899c1207b1a8a1