Aortic aneurism open repair surgery can cause spinal cord (SC) injury with 5-15% of patients developing paraparesis or paraplegia. Using a mouse model of transient aortic cross-clamping (ACC), we have previously found that the expression of proinflammatory microRNA increases in motoneurons (MNs) and endothelial cells (ECs) of ischemic SCs, and that global deletion decreases the percentage of paraplegia by 37.4% at 48-h post-ACC. Here, we investigated the cell-specific contribution of in choline acetyltransferase-positive (ChAT) neurons (that include all MNs of the SC) and ECs to SC injury after ACC. Mice lacking in ChAT neurons (MN--KO mice) developed 24.6% less paraplegia than control mice at 48-h post-ACC. In contrast, mice lacking in ECs (ECs--KO mice) experienced the same percentage of paraplegia as control mice, despite presenting smaller central cord edema. Unexpectedly, mice overexpressing in ChAT neurons were less likely than control mice to develop early paraplegia during the first day post-ACC, however they reached the same percentage of paraplegia at 48-h. In addition, all mice overexpressing in ECs (ECs--KI mice) were paraplegic at 48-h post-ACC. Altogether, our results suggest that activity in ChAT neurons protects the SC against ischemic injury during the first day post-ACC before becoming deleterious during the second day, which indicates that early and late paraplegias arise from different molecular malfunctions. These results point to the need to develop specific protective therapeutics aimed at inhibiting both the early and late deleterious events after open repair surgery of aortic aneurisms.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850917PMC
http://dx.doi.org/10.3389/fnmol.2022.788301DOI Listing

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