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    Delayed microglial depletion after spinal cord injury reduces chronic inflammation and neurodegeneration in the brain and improves neurological recovery in male mice.

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    Author
    Li, Yun
    Ritzel, Rodney M
    Khan, Niaz
    Cao, Tuoxin
    He, Junyun
    Lei, Zhuofan
    Matyas, Jessica J
    Sabirzhanov, Boris
    Liu, Simon
    Li, Hui
    Stoica, Bogdan A
    Loane, David J
    Faden, Alan I
    Wu, Junfang
    Show allShow less

    Date
    2020-09-14
    Journal
    Theranostics
    Publisher
    Ivyspring International Publisher
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.7150/thno.49199
    Abstract
    Neuropsychological deficits, including impairments in learning and memory, occur after spinal cord injury (SCI). In experimental SCI models, we and others have reported that such changes reflect sustained microglia activation in the brain that is associated with progressive neurodegeneration. In the present study, we examined the effect of pharmacological depletion of microglia on posttraumatic cognition, depressive-like behavior, and brain pathology after SCI in mice. Methods: Young adult male C57BL/6 mice were subjected to moderate/severe thoracic spinal cord contusion. Microglial depletion was induced with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX5622 administered starting either 3 weeks before injury or one day post-injury and continuing through 6 weeks after SCI. Neuroinflammation in the injured spinal cord and brain was assessed using flow cytometry and NanoString technology. Neurological function was evaluated using a battery of neurobehavioral tests including motor function, cognition, and depression. Lesion volume and neuronal counts were quantified by unbiased stereology. Results: Flow cytometry analysis demonstrated that PLX5622 pre-treatment significantly reduced the number of microglia, as well as infiltrating monocytes and neutrophils, and decreased reactive oxygen species production in these cells from injured spinal cord at 2-days post-injury. Post-injury PLX5622 treatment reduced both CD45int microglia and CD45hi myeloid counts at 7-days. Following six weeks of PLX5622 treatment, there were substantial changes in the spinal cord and brain transcriptomes, including those involved in neuroinflammation. These alterations were associated with improved neuronal survival in the brain and neurological recovery. Conclusion: These findings indicate that pharmacological microglia-deletion reduces neuroinflammation in the injured spinal cord and brain, improving recovery of cognition, depressive-like behavior, and motor function.
    Rights/Terms
    © The author(s).
    Keyword
    CSF1R
    cognition
    depression
    microglia
    spinal cord injury
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13918
    ae974a485f413a2113503eed53cd6c53
    10.7150/thno.49199
    Scopus Count
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