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Current treatments are limited by a lack of molecular data to inform novel therapeutic avenues. Previously, we showed that systemic treatment with the neuroprotective agent inosine improved bladder function following SCI in rats. Here, we applied integrated multi-omics analysis to explore molecular alterations in the bladder over time and their sensitivity to inosine following SCI. Canonical signaling pathways regulated by SCI included those associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation. Upstream regulator and causal network analysis predicted multiple effectors of DNA damage response signaling following injury, including poly-ADP ribose phosphorylase-1 (PARP1). Markers of DNA damage (\u03b3H2AX, ATM\/ATR substrates) and PARP activity were increased in bladder tissue following SCI and attenuated with inosine treatment. Inosine treatment also attenuated oxidative DNA damage in rat bladder cells in vitro. Proteomics analysis suggested that SCI induced changes in protein synthesis\u2013, neuroplasticity-, and oxidative stress\u2013associated pathways, a subset of which were shown in transcriptomics data to be inosine sensitive. 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