Fingolimod promotes angiogenesis and attenuates ischemic brain damage via modulating microglial polarization

Ke Shang, Jia He, Jing Zou, Chuan Qin, Li Lin, Luo Qi Zhou, Lin Lin Yang, Long Jun Wu, Wei Wang, Ke Bin Zhan, Dai Shi Tian

Research output: Contribution to journalArticle

Abstract

Introduction: Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. Methods: The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke. Results: In vivo, a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14. Conclusions: Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke.

Original languageEnglish (US)
Article number146509
JournalBrain research
Volume1726
DOIs
StatePublished - Jan 1 2020

Fingerprint

Stroke
Brain
Neuroprotective Agents
Phenotype
Immunomodulation
Fingolimod Hydrochloride
Microglia
Fluorescent Antibody Technique
Pathology
Staining and Labeling
Control Groups
Research
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Keywords

  • Angiogenesis
  • Ischemic stroke
  • Macrophage polarization
  • Microglia

Cite this

Shang, Ke ; He, Jia ; Zou, Jing ; Qin, Chuan ; Lin, Li ; Zhou, Luo Qi ; Yang, Lin Lin ; Wu, Long Jun ; Wang, Wei ; Zhan, Ke Bin ; Tian, Dai Shi. / Fingolimod promotes angiogenesis and attenuates ischemic brain damage via modulating microglial polarization. In: Brain research. 2020 ; Vol. 1726.
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abstract = "Introduction: Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. Methods: The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke. Results: In vivo, a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14. Conclusions: Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke.",
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Shang, K, He, J, Zou, J, Qin, C, Lin, L, Zhou, LQ, Yang, LL, Wu, LJ, Wang, W, Zhan, KB & Tian, DS 2020, 'Fingolimod promotes angiogenesis and attenuates ischemic brain damage via modulating microglial polarization', Brain research, vol. 1726, 146509. https://doi.org/10.1016/j.brainres.2019.146509

Fingolimod promotes angiogenesis and attenuates ischemic brain damage via modulating microglial polarization. / Shang, Ke; He, Jia; Zou, Jing; Qin, Chuan; Lin, Li; Zhou, Luo Qi; Yang, Lin Lin; Wu, Long Jun; Wang, Wei; Zhan, Ke Bin; Tian, Dai Shi.

In: Brain research, Vol. 1726, 146509, 01.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fingolimod promotes angiogenesis and attenuates ischemic brain damage via modulating microglial polarization

AU - Shang, Ke

AU - He, Jia

AU - Zou, Jing

AU - Qin, Chuan

AU - Lin, Li

AU - Zhou, Luo Qi

AU - Yang, Lin Lin

AU - Wu, Long Jun

AU - Wang, Wei

AU - Zhan, Ke Bin

AU - Tian, Dai Shi

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Introduction: Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. Methods: The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke. Results: In vivo, a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14. Conclusions: Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke.

AB - Introduction: Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. Methods: The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke. Results: In vivo, a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14. Conclusions: Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke.

KW - Angiogenesis

KW - Ischemic stroke

KW - Macrophage polarization

KW - Microglia

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