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Intravenous immune-modifying nanoparticles as a therapy for spinal cord injury in mice
- Source :
- Neurobiology of Disease, Vol 108, Iss, Pp 73-82 (2017)
- Publication Year :
- 2017
-
Abstract
- Intravenously infused synthetic 500 nm nanoparticles composed of poly(lactide-co-glycolide) are taken up by blood-borne inflammatory monocytes via a macrophage scavenger receptor (macrophage receptor with collagenous structure), and the monocytes no longer traffic to sites of inflammation. Intravenous administration of the nanoparticles after experimental spinal cord injury in mice safely and selectively limited infiltration of hematogenous monocytes into the injury site. The nanoparticles did not bind to resident microglia, and did not change the number of microglia in the injured spinal cord. Nanoparticle administration reduced M1 macrophage polarization and microglia activation, reduced levels of inflammatory cytokines, and markedly reduced fibrotic scar formation without altering glial scarring. These findings thus implicate early-infiltrating hematogenous monocytes as highly selective contributors to fibrosis that do not play an indispensable role in gliosis after SCI. Further, the nanoparticle treatment reduced accumulation of chondroitin sulfate proteoglycans, increased axon density inside and caudal to the lesion site, and significantly improved functional recovery after both moderate and severe injuries to the spinal cord. These data provide further evidence that hematogenous monocytes contribute to inflammatory damage and fibrotic scar formation after spinal cord injury in mice. Further, since the nanoparticles are simple to administer intravenously, immunologically inert, stable at room temperature, composed of an FDA-approved material, and have no known toxicity, these findings suggest that the nanoparticles potentially offer a practical treatment for human spinal cord injury.
- Subjects :
- 0301 basic medicine
Pathology
Macrophage
Monocyte
Monocytes
0302 clinical medicine
Nanotechnology
Gliosis
Spinal cord injury
Polyglactin 910
Microglia
Macrophage receptor with collagenous structure
medicine.anatomical_structure
Neurology
Spinal Cord
Administration, Intravenous
Female
medicine.symptom
medicine.medical_specialty
Macrophage polarization
Inflammation
Motor Activity
Article
lcsh:RC321-571
Proinflammatory cytokine
03 medical and health sciences
Cicatrix
medicine
Animals
Immunologic Factors
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Spinal Cord Injuries
Cell Size
business.industry
Macrophages
Recovery of Function
Spinal cord
medicine.disease
Fibrosis
Axons
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Chondroitin Sulfate Proteoglycans
Nanoparticles
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease, Vol 108, Iss, Pp 73-82 (2017)
- Accession number :
- edsair.doi.dedup.....08ac09baca50f8f850c5d6116a2039ed