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Authors & Affiliations
David Dubayle, Nicolas Rebergue, Yann Godfrin, Jean-Luc Morel, Sighild Lemarchant
Abstract
Astronauts endure repetitive episodes of hypergravity (HG) during takeoff and landing of spaceflights, and also in space due to microgravity. We have recently shown subtle BBB breakdown in a mouse model of centrifugation-induced HG (Dubayle et al., 2023); here we have evaluated if the blood-spinal cord barrier (BSCB) was also damaged in this model.Eight-week-old C57Bl/6J male mice were subjected to HG in a centrifuge at 2g for 24h, while control mice stayed in normogravity (N=9/group). Mice were sacrificed after centrifugation, and thoracic spinal cords collected for immunohistochemistry. For each mouse, six spinal cord sections of 5 µm thick and 100 µm away from each other were sliced using a microtome. Claudin-5/ZO-1 and occludin/collagen IV co-stainings were performed to evaluate the immunoreactive area of tight junction proteins normalized to that of collagen IV-positive vessels.A significant weight drop was measured in HG 2g mice compared to control 1g mice (-2.4g, p=0.0002), despite no difference in food intake nor glycemia between groups (p=0.1274 and p=0.7572, respectively).Interestingly, a significant decrease in occludin level was measured in the spinal cord of HG 2g mice compared to that of control 1g mice (-28.6%, p=0.0378). A non-significant trend towards a decreased level was also observed for claudin-5 (-20.6%, p=0.1130). No difference in ZO-1 level was observed (p=0.2000).This is the first study to evidence BSCB alterations in the context of hypergravity. We will now investigate if the reduction of occludin level is accompanied by the presence of blood-derived proteins into spinal cord parenchyma.