SVCT2 Promotes Neural Stem/Progenitor Cells Migration Through Activating CDC42 After Ischemic Stroke

Abstract

Ischemic stroke is one of the most leading diseases causing death/long-term disability worldwide. Activating endogenous neural stem/progenitors cells (NSPCs), lining in the subventricular zone (SVZ) and dentate gyrus, facilitates injured brain tissue recovery in both short and long-term experimental settings. While, only a few proliferated NSPCs migrate toward the lesions to enhance endogenous repair after ischemia. Here, the results indicated that the functional recovery was evidently improved and the infarct volume was significantly reduced with ascorbic acid (AA) treatment in a dose-dependent manner from 125 to 500 mg/Kg, and the suitable therapeutic concentration was 250 mg/Kg. The possible mechanism might be due to activating sodium-vitamin C cotransporter 2 (SVCT2), which was down-regulated in SVZ after ischemia. Furthermore, immunostaining images depicted the number of migrated NSPCs from SVZ were significantly increased with 250 mg/Kg AA treatment or SVCT2 overexpression under the physiological and pathological condition in vivo. Besides, the data also represented that 250 mg/Kg AA or SVCT2 overexpression facilitated NSPCs migration via promoting F-actin assembling in the manner of up-regulating CDC42 expression using oxygen-glucose deprivation in vitro. Collectively, the present study indicates that SVCT2 promotes NSPCs migration through CDC42 activation to facilitate F-actin assembling, which enlarges the therapeutic scope of AA and the role of SVCT2 in NSPCs migration after brain injury.

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

“…Corner test was performed to assess the neurological impairment as previously described (Yang et al, 2019 ). Briefly, mice were placed half way between two angled boards with a 30-degree corner, and the head was oriented toward the corner.…”

“…Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide, and imposed heavy socioeconomic burden (George and Steinberg, 2015 ; Prabhakaran et al, 2015 ; Petro et al, 2016 ; Koh and Park, 2017 ; Yang et al, 2019 ). Once ischemia ictus, it always creates an irreversible infarct core resulting from rapid neural cell death of parenchyma in the ischemic epicenter (Petro et al, 2016 ).…”

“…Herein, exploring the feasible therapeutic strategies to diminish penumbra deterioration or to restore the penumbra has aroused great attention for researchers after ischemic stroke. Cumulative evidence has indicated that activation of endogenous neural stem cells (eNSCs), which are specifically resided in the dentate gyrus (DG) and subventricular zone (SVZ), could proliferate in situ , migrate toward penumbra, and differentiated into three main neural subtype cells, benefiting penumbra rehabilitation after ischemic stroke (Hao et al, 2014 ; Huang and Zhang, 2019 ; Yang et al, 2019 ; Dillen et al, 2020 ). However, previous studies also reveal that the majority of eNSCs migrated from SVZ differentiate into astrocytes forming glial scar in penumbra after brain injury (Hermann et al, 2014 ; Grégoire et al, 2015 ).…”

Targeting CYP2J2 to Enhance the Anti-Glioma Efficacy of Cannabinoid Receptor 2 Stimulation by Inhibiting the Pro-Angiogenesis Function of M2 Microglia

“…Total protein from the primary microglial cells treated with JWH133 alone and co-treated with JWH133 and AM630 was lysed in ice-cold RIPA (Sigma-Aldrich, St. Louis, MO, United States) supplemented with protease inhibitor cocktail (Roche, Indianapolis, IN, United States) as described in a previous study (32). The protein concentration was determined by an enhanced BCA Protein Assay Kit (Beyotime, Beijing, China).…”

Ambroxol Improves Neuronal Survival and Reduces White Matter Damage through Suppressing Endoplasmic Reticulum Stress in Microglia after Intracerebral Hemorrhage

“…The rotarod test was performed as described by our previous work [16]. The speed was set to increase gradually from 5 to 35 rpm, and the latency to fall (or cling to and spin with the rod for three full rotations) within 3 min was recorded for statistical analysis.…”