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A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia
A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia
- Source :
- Translational Stroke Research. 7:548-561
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- White matter injury induced by ischemic stroke elicits sensorimotor impairments, which can be further deteriorated by persistent proinflammatory responses. We previously reported that delayed and repeated treatments with omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve spatial cognitive functions and hippocampal integrity after ischemic stroke. In the present study, we report a post-stroke n-3 PUFA therapeutic regimen that not only confers protection against neuronal loss in the gray matter but also promotes white matter integrity. Beginning 2 hours after 60 minutes of middle cerebral artery occlusion (MCAO), mice were randomly assigned to receive intraperitoneal docosahexaenoic acid (DHA) injections (10 mg/kg, daily for 14 days), alone or in combination with dietary fish oil (FO) supplements starting 5 days after MCAO. Sensorimotor functions, gray and white matter injury, and microglial responses were examined up to 28 days after MCAO. Our results showed that DHA and FO combined treatment facilitated long-term sensorimotor recovery and demonstrated greater beneficial effect than DHA injections alone. Mechanistically, n-3 PUFAs not only offered direct protection on white matter components, such as oligodendrocytes, but also potentiated microglial M2 polarization, which may be important for white matter repair. Notably, the improved white matter integrity and increased M2 microglia were strongly linked to the mitigation of sensorimotor deficits after stroke upon n-3 PUFA treatments. Together, our results suggest that post-stroke DHA injections in combination with FO dietary supplement benefit white matter restoration and microglial responses, thereby dictating long-term functional improvements.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Time Factors
Docosahexaenoic Acids
Ischemia
Nerve Tissue Proteins
Hippocampal formation
Corpus callosum
Article
Corpus Callosum
Proinflammatory cytokine
White matter
Mice
03 medical and health sciences
0302 clinical medicine
Antigens, CD
Leukoencephalopathies
Internal medicine
medicine
Animals
Cell Proliferation
chemistry.chemical_classification
Microglia
business.industry
General Neuroscience
Calcium-Binding Proteins
Microfilament Proteins
Myelin Basic Protein
medicine.disease
Mice, Inbred C57BL
Stroke
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Eicosapentaenoic Acid
chemistry
Ischemic Attack, Transient
Docosahexaenoic acid
Cerebrovascular Circulation
Neurology (clinical)
Nervous System Diseases
Cardiology and Cardiovascular Medicine
business
030217 neurology & neurosurgery
Polyunsaturated fatty acid
Subjects
Details
- ISSN :
- 1868601X and 18684483
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Translational Stroke Research
- Accession number :
- edsair.doi.dedup.....d113f31f0f5b2bf3fd94f918d129c737
- Full Text :
- https://doi.org/10.1007/s12975-016-0502-6