Abstract
Locomotion speed changes appear following hippocampal injury. We used a hippocampal penetrating brain injury mouse model to analyze other kinematic changes. We found a significant decrease in locomotion speed in both open-field and tunnel walk tests. We described a new quantitative method that allows us to analyze and compare the displacement curves between mice steps. In the tunnel walk, we marked mice with indelible ink on the knee, ankle, and metatarsus of the left and right hindlimbs to evaluate both in every step. Animals with hippocampal damage exhibit slower locomotion speed in both hindlimbs. In contrast, in the cortical injured group, we observed significant speed decrease only in the right hindlimb. We found changes in the displacement patterns after hippocampal injury. Mesenchymal stem cell-derived extracellular vesicles had been used for the treatment of several diseases in animal models. Here, we evaluated the effects of intranasal administration of endometrial mesenchymal stem cell-derived extracellular vesicles on the outcome after the hippocampal injury. We report the presence of vascular endothelial growth factor, granulocyte–macrophage colony-stimulating factor, and interleukin 6 in these vesicles. We observed locomotion speed and displacement pattern preservation in mice after vesicle treatment. These mice had lower pyknotic cells percentage and a smaller damaged area in comparison with the nontreated group, probably due to angiogenesis, wound repair, and inflammation decrease. Our results build up on the evidence of the hippocampal role in walk control and suggest that the extracellular vesicles could confer neuroprotection to the damaged hippocampus.
Highlights
Hippocampus is a susceptible brain structure to neurodegenerative diseases (Nikonenko et al, 2009), mainly related to memory, learning, and spatial orientation (Andersen et al, 2007)
extracellular vesicles (EVs) secreted by these cells were isolated, with a multistep centrifugation and ultrafiltration method. Endometrial Mesenchymal Stem Cells (eMSC)–EV fractions were characterized according to current standards
We demonstrated the expression of Tsg101 in eMSC–EVs extracts using Western blot (Figure 2C)
Summary
Hippocampus is a susceptible brain structure to neurodegenerative diseases (Nikonenko et al, 2009), mainly related to memory, learning, and spatial orientation (Andersen et al, 2007). There is no model that affects hippocampus without damage of the cortex This model reflects hippocampal injury caused by mild to moderate traumatic brain injury (TBI) in the hippocampus. Endometrial MSCs (eMSCs) can be obtained without invasive procedures (Du et al, 2016) and possess a higher proliferation rate and migration capacity compared with MSCs obtained from other sources (Alcayaga-Miranda et al, 2015; Du et al, 2016). These cells can be differentiated into several lineages, including neurons (Meng et al, 2007). Further investigation is required to determine the role of eMSC–EVs in neuroprotection from direct damage in mouse brain tissue
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