Combined Deletion of Mitofusin 2 in Adipose-Mesenchymal Derived Stem Cells and Melatonin Offers Additional Benefits on Protecting the Brain Against Acute Ischemic Stroke in Rat.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background and Aims: Ischemic stroke (IS) remains the third leading cause of death, and the treatment of acute ischemic stroke (AIS) is still a formidable challenge to clinicians. This study tested the hypothesis that combined silencing Mnf2 gene in adipose-derived mesenchymal stem cells (ADMSCs sil-Mnf2 ) and melatonin (Mel) therapy was superior to monotherapy on attenuating the brain infarct volume (BIV) and improving neurological function in AIS rats. Results: In vitro and in vivo studies were conducted. In vitro results showed that as compared with the controls ( i.e., ADMSCs/N2a cells), the cellular/protein levels of oxidative stress/reactive oxygen species (ROS)/mitochondrial and DNA damaged/apoptotic/cell stress signaling (tumor necrosis factor [TNF] receptor associated factor 6/ apoptosis signal regulating kinase/MKK 4/7 /JUN/ERK 1/2 /c-Jun) biomarkers were significantly increased in these cells treated by H 2 O 2 that were significantly reversed by ADMSCs sil-Mnf2 or Mel and further significantly reversed by combined therapy (all p < 0.0001). Animals were categorized into groups 1 (sham-operated control)/2 (AIS)/3 (AIS + Mel)/4 (AIS + ADMSCs sil-Mnf2 )/5 (AIS + Mel-ADMSCs sil-Mnf2 ) and euthanized by day 28 after AIS. By day 28, the BIV and the brain infarct area (BIA) were lowest in group 1/highest in group 2/significantly lower in group 5 than in groups 3 and 4/signi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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