Ischemic stroke often causes severe neurological impairments. Our previous studies showed that Col003, a heat shock protein (HSP47) inhibitor, has neuroprotective effects in acute ischemic stroke, but its role in chronic ischemic stroke remains unclear. This study investigated gene changes in ischemic brain tissue of rats treated with Col003 after chronic ischemic stroke. Rats with middle cerebral artery occlusion (MCAO) received Col003 injections via tail vein daily for 14 days. Neurological function and cerebral infarct volume were measured post-ischemia. Rat brain tissues from Sham, Vehicle, and Col003 groups were analyzed by western blot (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and RNA-Seq. Fourteen days post-MCAO, Col003 treatment significantly decreased cerebral infarct volume and enhanced neurological function scores in rats. There were 1956 genes up-regulated (Vehicle vs. Sham) and 251 genes down-regulated (Col003 vs. Vehicle) by RNA-Seq analysis, and 136 differentially expressed genes (DEGs) were identified by Venn diagram analysis. We screened genes closely associated with ischemic stroke, including lipocalin-2 (LCN2), from the top 20 significantly DEGs. Pathway enrichment analysis of DEGs showed that JAK-STAT pathway was strongly associated with chronic ischemic stroke. RT-qPCR and WB showed that LCN2 was upregulated in peri-infarct brain tissue at 14 days after ischemic stroke, and LCN2 was significantly reduced after Col003 treatment. Col003 decreased JAK2/STAT3 phosphorylation in ischemic brain tissue. In rats with chronic ischemic stroke, Col03 may lessen the size of the cerebral infarction and neurological impairments by blocking LCN2 through the JAK2/STAT3 signaling pathway.

Ischemic stroke often causes severe neurological impairments. Our previous studies showed that Col003, a heat shock protein (HSP47) inhibitor, has neuroprotective effects in acute ischemic stroke, but its role in chronic ischemic stroke remains unclear. This study investigated gene changes in ischemic brain tissue of rats treated with Col003 after chronic ischemic stroke. Rats with middle cerebral artery occlusion (MCAO) received Col003 injections via tail vein daily for 14 days. Neurological function and cerebral infarct volume were measured post-ischemia. Rat brain tissues from Sham, Vehicle, and Col003 groups were analyzed by western blot (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and RNA-Seq. Fourteen days post-MCAO, Col003 treatment significantly decreased cerebral infarct volume and enhanced neurological function scores in rats. There were 1956 genes up-regulated (Vehicle vs. Sham) and 251 genes down-regulated (Col003 vs. Vehicle) by RNA-Seq analysis, and 136 differentially expressed genes (DEGs) were identified by Venn diagram analysis. We screened genes closely associated with ischemic stroke, including lipocalin-2 (LCN2), from the top 20 significantly DEGs. Pathway enrichment analysis of DEGs showed that JAK-STAT pathway was strongly associated with chronic ischemic stroke. RT-qPCR and WB showed that LCN2 was upregulated in peri-infarct brain tissue at 14 days after ischemic stroke, and LCN2 was significantly reduced after Col003 treatment. Col003 decreased JAK2/STAT3 phosphorylation in ischemic brain tissue. In rats with chronic ischemic stroke, Col03 may lessen the size of the cerebral infarction and neurological impairments by blocking LCN2 through the JAK2/STAT3 signaling pathway.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.