Abstract Body: Background
The latest Global Burden of Disease study indicates that stroke remains the second major cause of death. Promising protective effects have been shown in most studies of ischemic stroke (IS) protection in preclinical animal models, but have failed to enter clinical trials. The objective of this study is to investigate the brain cytoprotective effects of the natural compound MBS-1 in IS, using a novel, rigorous, and feasible paradigm inspired by Stroke Preclinical Assessment Network (SPAN).
Methods
This study performs the SPAN methodology in two centers, and takes including a randomization, blinding, and placebo control approach, utilizing a novel multi-arm (multiple groups) and multi-stage (multiple time points) design along with the establishment of comorbidity models. Specifically, the study uses wild-type (WT) C57BL/6J mice (8~10 weeks, Half male and half female), aged mice, and diabetic mice to establish a middle cerebral artery occlusion (MCAO) model. We assess the recovery of motor and sensory functions using behavioral tests such as the corner test, cylinder test, modified neurological severity score (mNSS), and Longa score. To identify the protein expression and localization, we use Western blot analysis and immunofluorescence staining. The infarct volume is detected using magnetic resonance imaging (MRI) or triphenyltetrazolium chloride (TTC) staining. Transmission electron microscopy (TEM) and Golgi staining are applied to assess neuronal morphology and number, while Nissl and TUNEL staining are used to evaluate neuronal function and apoptosis levels.
Results
In the permanent MCAO model induced by chloride iron in WT young mice, MBS-1 significantly reduces the infarct volume, improves neurological function, and decreases neuronal apoptosis. In the MCAO/reperfusion (MCAO/R) model conducted by intraluminal filament in WT young mice, MBS-1 also effectively reduces the infarct volume, enhances neurological function, and decreases neuronal apoptosis. While in the MCAO/R model conducted by intraluminal filament in WT aged mice, MBS-1 visibly improves the survival rate of mice. Furthermore, in the MCAO/R model of diabetic mice, MBS-1 significantly reduces the infarct volume and improves neurological function.
Conclusion
Using SPAN paradigm, MBS-l exhibits brain cytoprotection in various IS models.
Key words
Stroke Preclinical Assessment Network, MBS-1, ischemic stroke, brain cytoprotection