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Anti-inflammation conferred by stimulation of CD200R1 via Dok1 pathway in rat microglia after germinal matrix hemorrhage

Feng, Zhanhui, Ye, Lan, Klebe, Damon, Ding, Yan, Guo, Zhen-Ni, Flores, Jerry J, Yin, Cheng, Tang, Jiping, Zhang, John H·2019·Journal of Cerebral Blood Flow & Metabolism
DOI 10.1177/0271678x17725211
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Abstract

CD200 has been reported to be neuroprotective in neurodegenerative diseases. However, the potential protective effects of CD200 in germinal matrix hemorrhage (GMH) have not been investigated. We examined the anti-inflammatory mechanisms of CD200 after GMH. A total of 167 seven-day-old rat pups were used. The time-dependent effect of GMH on the levels of CD200 and CD200 Receptor 1 (CD200R1) was evaluated by western blot. CD200R1 was localized by immunohistochemistry. The short-term (24 h) and long-term (28 days) outcomes were evaluated after CD200 fusion protein (CD200Fc) treatment by neurobehavioral assessment. CD200 small interfering RNA (siRNA) and downstream of tyrosine kinase 1 (Dok1) siRNA were injected intracerebroventricularly. Western blot was employed to study the mechanisms of CD200 and CD200R1. GMH induced significant developmental delay and caused impairment in both cognitive and motor functions in rat pups. CD200Fc ameliorated GMH-induced damage. CD200Fc increased expression of Dok1 and decreased IL-1beta and TNF-alpha levels. CD200R1 siRNA and Dok1 siRNA abolished the beneficial effects of CD200Fc, as demonstrated by enhanced expression levels of IL-1beta and TNF-alpha. CD200Fc inhibited GMH-induced inflammation and this effect may be mediated by CD200R1/Dok1 pathway. Thus, CD200Fc may serve as a potential treatment to ameliorate brain injury for GMH patients.

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Metadata

Authors
Feng, Z., Ye, L., Klebe, D., Ding, Y., Guo, Z.-N., Flores, J. J., Yin, C., Tang, J., & Zhang, J. H.
Affiliations
  • Department of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
  • Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA
Venue
Journal of Cerebral Blood Flow & Metabolism
Publisher
SAGE Publications
Published
2017-08-09
Volume
39
Issue
1
Pages
97-107
ISSN
  • 0271-678X
  • 1559-7016
DOI
10.1177/0271678x17725211
Cited by
23
References
1
Language
en
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)

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