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Abstract 12536: Nanoliposomal Treatment Reduces Stroke Injury Following Middle Cerebral Artery Occlusion in Mice
- Source :
- Circulation. 144
- Publication Year :
- 2021
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2021.
-
Abstract
- Introduction: Neuroprotective strategies for stroke are lacking leading to significant disability and death. Liposomes (phospholipid particles) are commonly used as molecular carriers of therapeutic agent cargos. We previously showed that cargo-less nanoliposomes (NL, Hypothesis: NL will preserve neuroblastoma cell viability in the setting of hypoxic injury and will reduce functional and histologic injury in mice following middle cerebral artery occlusion (MCAO). Methods: SH-SY5Y neuroblastoma cells were exposed to 20-hour physoxic (5% oxygen) condition or hypoxic (1% oxygen) condition without or with NL (100 or 300 μg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment scoring was compared as well as post-mortem brain infarction size. Results: Neuroblastoma cells showed reduced viability following hypoxia that was reversed by treatment with NL. NL increased gene expression of HO-1, NQO1 and SOD1 compared to untreated controls. NL-treated mice showed reduced neurologic function impairment and reduced brain infarct size compared to controls (18.8±2% versus 27.3±2.3%, p=0.017, see Figure). Conclusions: Cargo-less NL reduced functional and structural stroke injury in mice subjected to MCAO likely mediated in part through induction of an antioxidant stress response. NL is a candidate novel agent to mitigate stroke injury.
- Subjects :
- Physiology (medical)
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15244539 and 00097322
- Volume :
- 144
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi...........a11109a9acef38806d3b6a2d6f21400e