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In our earlier research, we identified a neuron-derived circular RNA (circRNA), circular oxoglutarate dehydrogenase (CircOGDH), as a promising therapeutic target for acute ischaemic stroke. This study dedicated to explore a prospective preliminary strategy of CircOGDH-based NP delivered to the ischaemic penumbra region in middle cerebral artery occlusion\/reperfusion (MCAO\/R) mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Immunofluorescence in primary cortex neurons and in vivo fluorescence imaging revealed endocytosis of Poly(lactide-co-glycolide) (PLGA) poly amidoamine(PAMAM)@CircOGDH small interfering RNA (siRNA) NPs. Western blotting analysis and CCK8 assay were performed to evaluate the apoptotic level in ischaemic neurons treated with PLGA\u2013PAMAM@CircOGDH siRNA NPs. Quantitative reverse transcription PCR experiments, mice behaviour test, T2 MRI analysis, Nissl and TdT-mediated dUTP nick end labeling (TUNEL) co-staining were performed to evaluate the apoptosis level of ischaemic penumbra neurons in MCAO\/R mice. Biosafety evaluation of NPs in MCAO\/R mice was detected by blood routine examination, liver and kidney function examination and HE staining.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PLGA\u2013PAMAM@CircOGDH siRNA NPs were successfully assembled. Endocytosis of PLGA\u2013PAMAM@CircOGDH siRNA NPs in ischaemic neurons alleviated neuronal apoptotic level in vitro and in vivo. Furthermore, mice behaviour test showed that the neurological defects of MCAO\/R mice were significantly alleviated after the tail injection of PLGA\u2013PAMAM@CircOGDH siRNA NPs, and no toxic effects were observed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In conclusion, our results suggest that PLGA\u2013PAMAM@CircOGDH siRNA NPs can be delivered to the ischaemic penumbra region and alleviate neuron apoptosis in MCAO\/R mice and in ischaemic neurons; therefore, our study provides a desirable approach for using circRNA-based NPs for the treatment of ischaemic stroke.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/svn-2022-002009","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T13:22:54Z","timestamp":1686921774000},"page":"134-144","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Penumbra-targeted CircOGDH siRNA-loaded nanoparticles alleviate neuronal apoptosis in focal brain ischaemia"],"prefix":"10.1136","volume":"9","author":[{"given":"Yanfang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology and Stroke Center, Jinan University First Affiliated Hospital, Guangzhou, Guangdong, China"},{"name":"Department of Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China"},{"name":"Key Lab of Guangzhou Basic and Translational Research of Pan-vascular Diseases, The First Affiliated Hospital of Jinan University, Guangzhou, 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