Abstract
The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and bioluminescent image (BLI) after lentiviral transduction and MNP labeling. At random, the animals were divided into 5 groups (control-G1, and experimental G2-G5). The photothrombotic stroke induction was confirmed by local blood perfusion reduction and Triphenyltetrazolium chloride (TTC), and MSC in the G3 and G5 groups were implanted after 24 h, with BLI and near-infrared fluorescence image (NIRF) tracking these cells at 28 h, 2, 7, 14, and 28 days. During a 28-day period, the G5 also conducted physical training, whereas the G4 simply did the training. At 0, 7, 14, and 28 days, the animals were functionally tested using a cylinder test and a spontaneous motor activity test. MNP internalization in MSC was confirmed using brightfield and fluorescence microscopy. In relation to G1 group, only 3% of cell viability reduced. The G2–G5 groups showed more than 69% of blood perfusion reduction. The G5 group performed better over time, with a progressive recovery of symmetry and an increase of fast vertical movements. Up to 7 days, BLI and NIRF followed MSC at the damaged site, demonstrating a signal rise that could be connected to cell proliferation at the injury site during the acute phase of stroke. Local MSC therapy mixed with physical activity resulted in better results in alleviating motor dysfunction, particularly during the acute period. When it comes to neurorehabilitation, this alternative therapy could be a suitable fit.
Highlights
Ischemic stroke still represents a serious threat to human health and economic systems, with an estimated 116 million healthy lives lost each year due to stroke-related death and disability [1]
In the mesenchymal stem cell (MSC) unlabeled with magnetic nanoparticles (MNP) images (Figure 2A,B), it is possible to visualize the cell nucleus in blue (DAPI) by fluorescence microscopy (Figure 2A) and the absence of Prussian blue staining (Figure 2B) due to MNP absence
In images of MSC labeled with MNP (Figure 2C,D), fluorescence microscopy allowed the visualization of MNP internalized into MSC cytoplasm in red due to the presence of fluorophore in the visible spectrum (558/580 nm) using the TRITC filter, and the MSC nucleus highlighted in blue by DAPI staining (Figure 2C)
Summary
Ischemic stroke still represents a serious threat to human health and economic systems, with an estimated 116 million healthy lives lost each year due to stroke-related death and disability [1]. Stroke is one of the three leading causes of death and disability among age-related non-communicable diseases worldwide, followed by ischemic heart disease, and dementia [3]. Treatment for functional rehabilitation after stroke is still limited, despite breakthroughs in pharmacological and surgical therapy [4]. A few patients receive effective treatment due to the limited therapeutic time window (8 h). In this scenario, novel treatments aimed at promoting brain balance, reducing the infarct region, and accelerating neurological recovery appear to be urgently needed [5,6]
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