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Published on: November 14, 2020
Impact of NBP on acute ischemic stroke: Tracking therapy effect on neuroinflammation
Ze Wang1, Shuwei Bai2, Yaying Song2
1Department of Neurology, Punan Hospital, Pudong New District, Shanghai 200125, China; Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Background:
Ischemic stroke is the leading cause of death and long-term disability worldwide. After stroke, microglia exhibit not only pro-inflammatory phenotype to aggravate the neuroinflammation, but also anti-inflammatory phenotype to play a neuroprotective role. Studies on the spatial and temporal changes in microglia and the underlying mechanisms help to elucidate the inflammatory cascade after stroke. The regulation of microglia polarization provides new insights for the intervention of post-stroke inflammation.
Objective:
We aimed to investigate the phenotypic change of microglia in the acute phase of ischemic stroke and the effects of Dl-3-n-butylphthalide (NBP) on microglia. TSPO-PET was used to image microglia and evaluate the efficacy of NBP.
Methods:
We constructed an MCAO model in rats and administered NBP daily. The infarct volumes in the NBP-treated and control groups were measured. TSPO-PET/CT was used to demonstrate the activation of microglia and the effects of NBP. Additionally, we investigated the effects of NBP on TSPO expression. In vitro, microglia were exposed to glucose oxygen deprivation, and the effects of NBP on microglia and TSPO expression were verified.
Results:
NBP improved neurological severity scores and reduced infarct volume in the acute phase of ischemic stroke. NBP facilitated microglia to adopt the anti-inflammatory phenotype and reduce the pro-inflammatory phenotype. NBP decreased the expressions of inflammatory cytokines. TSPO-PET/CT observed increase in uptake in the infarct lesion, and this uptake was reduced in response to NBP. NBP reduced TSPO expression in microglia after stroke. In vitro experiments further verified that NBP facilitated the transition of microglia towards the anti-inflammatory phenotype, and inhibited inflammatory cytokine secretion and TSPO expression.
Conclusion:
We illustrated that NBP fosters the shift of microglia towards the anti-inflammatory phenotype while diminishing their inclination towards the pro-inflammatory phenotype, thereby exerting neuroprotective effects. NBP reduces TSPO expression in microglia, which can be observed by TSPO-PET/CT imaging.
Insights
Dl-3-n-butylphthalide (NBP) reduces brain damage after ischemic stroke by shifting microglia to an anti-inflammatory state. This neuroprotective effect, observed via TSPO-PET/CT imaging, involves decreased neuroinflammation and reduced TSPO expression.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Ischemic stroke is a major cause of death and disability globally.
- Microglia play dual roles in neuroinflammation, exhibiting both pro-inflammatory and anti-inflammatory phenotypes post-stroke.
- Understanding microglia polarization is crucial for developing interventions for post-stroke inflammation.
Purpose of the Study:
- To investigate microglial phenotypic changes during the acute phase of ischemic stroke.
- To evaluate the effects of Dl-3-n-butylphthalide (NBP) on microglia polarization and neuroprotection.
- To assess the utility of TSPO-PET/CT imaging in evaluating NBP's efficacy.
Main Methods:
- Middle cerebral artery occlusion (MCAO) rat model of ischemic stroke.
- Daily administration of NBP, with measurements of infarct volume and neurological scores.
- TSPO-PET/CT imaging to visualize microglia activation and assess NBP's impact on TSPO expression.
- In vitro studies using oxygen-glucose deprivation in microglia to confirm NBP's effects.
Main Results:
- NBP treatment significantly improved neurological scores and reduced infarct volume in the acute stroke phase.
- NBP promoted a shift in microglia towards an anti-inflammatory phenotype, reducing pro-inflammatory markers and inflammatory cytokines.
- TSPO-PET/CT imaging showed reduced tracer uptake in NBP-treated rats, correlating with decreased TSPO expression in microglia.
- In vitro experiments confirmed NBP's ability to promote anti-inflammatory microglia polarization and reduce TSPO expression.
Conclusions:
- NBP exerts neuroprotective effects in ischemic stroke by promoting microglia to adopt an anti-inflammatory phenotype.
- NBP effectively diminishes the pro-inflammatory microglial response, mitigating neuroinflammation.
- TSPO expression in microglia is reduced by NBP, a change detectable by TSPO-PET/CT imaging.
