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Periventricular white matter damage (PWMD) is a predominant neurologic lesion in preterm infants who survive brain injury. In this study, we assessed the global changes and characteristics of transcriptome of long non-coding RNAs (lncRNAs) in the brain tissues of rats with PWMD. The lncRNA expression profiles of brain tissue samples from rats with PWMD and paired sham tissues were obtained using deep RNA sequencing. Nine lncRNAs were selected for real time-quantitative PCR (RT-qPCR) validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based approaches were used to investigate the biological functions and signaling pathways affected by the closest coding genes of differentially expressed lncRNAs. Many lncRNAs were dysregulated in the brain tissue of the rats with PWMD, suggesting that they play a role in the condition. Two hundred and eighty-nine lncRNAs (P < 0.05 and fold change >= 2.0) were differentially expressed in the PWMD rat brains. One hundred and twenty-three lncRNAs were significantly upregulated and 166 were significantly down-regulated. qRT-PCR confirmed the expression profiles of six among nine randomly selected lncRNAs. One of the most highly enriched signal pathways were inflammatory mediator regulation of transient receptor potential (TRP) channels and neurotrophin signaling pathway, respectively. This study identified differentially expressed lncRNAs between sham and PWMD groups, and these lncRNAs may provide a new clue for mechanism of PWMD.