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Improved locomotor recovery after contusive spinal cord injury in Bmal1 −/− mice is associated with protection of the blood spinal cord barrier
- Source :
- Scientific Reports, Vol 10, Iss 1, Pp 1-18 (2020), Scientific Reports
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- The transcription factor BMAL1/ARNTL is a non-redundant component of the clock pathway that regulates circadian oscillations of gene expression. Loss of BMAL1 perturbs organismal homeostasis and usually exacerbates pathological responses to many types of insults by enhancing oxidative stress and inflammation. Surprisingly, we observed improved locomotor recovery and spinal cord white matter sparing in Bmal1−/− mice after T9 contusive spinal cord injury (SCI). While acute loss of neurons and oligodendrocytes was unaffected, Bmal1 deficiency reduced the chronic loss of oligodendrocytes at the injury epicenter 6 weeks post SCI. At 3 days post-injury (dpi), decreased expression of genes associated with cell proliferation, neuroinflammation and disruption of the blood spinal cord barrier (BSCB) was also observed. Moreover, intraspinal extravasation of fibrinogen and immunoglobulins was decreased acutely at dpi 1 and subacutely at dpi 7. Subacute decrease of hemoglobin deposition was also observed. Finally, subacutely reduced levels of the leukocyte marker CD45 and even greater reduction of the pro-inflammatory macrophage receptor CD36 suggest not only lower numbers of those cells but also their reduced inflammatory potential. These data indicate that Bmal1 deficiency improves SCI outcome, in part by reducing BSCB disruption and hemorrhage decreasing cytotoxic neuroinflammation and attenuating the chronic loss of oligodendrocytes.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
CD36
lcsh:Medicine
Inflammation
Spinal cord injury
medicine.disease_cause
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
lcsh:Science
Spinal Cord Injuries
Neuroinflammation
Blood-brain barrier
Mice, Knockout
Multidisciplinary
biology
business.industry
lcsh:R
ARNTL Transcription Factors
Recovery of Function
medicine.disease
Spinal cord
Extravasation
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
medicine.anatomical_structure
biology.protein
Diseases of the nervous system
lcsh:Q
medicine.symptom
Transcriptome
business
Locomotion
030217 neurology & neurosurgery
Homeostasis
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....9051beca47a834cbf72707b999daccd1
- Full Text :
- https://doi.org/10.1038/s41598-020-71131-6