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Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
- Source :
- Theranostics, Theranostics, 2021, 11 (18), pp.8640-8659. ⟨10.7150/thno.61833⟩, Theranostics, Ivyspring International Publisher, 2021, 11 (18), pp.8640-8659. ⟨10.7150/thno.61833⟩
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.
- Subjects :
- Male
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV]Life Sciences [q-bio]
primates
Medicine (miscellaneous)
microglia
Gene Expression
Transcriptome
Mice
0302 clinical medicine
Oral administration
Receptor
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Spinal cord injury
ComputingMilieux_MISCELLANEOUS
0303 health sciences
Microglia
rodent
medicine.anatomical_structure
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
medicine.symptom
Cheirogaleidae
Spinal cord pathology
Research Paper
proliferation
Neurogenesis
Central nervous system
Mice, Transgenic
Anisoles
Lesion
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neuroinflammation
Spinal Cord Injuries
030304 developmental biology
Cell Proliferation
Inflammation
business.industry
Recovery of Function
Functional recovery
medicine.disease
spinal cord injury
Mice, Inbred C57BL
Disease Models, Animal
Pyrimidines
Neuroinflammatory Diseases
Cancer research
business
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 18387640
- Volume :
- 11
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....3ddcfd533152196712602d88cb3c8fc5