Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice

Version 1 : Received: 12 August 2021 / Approved: 13 August 2021 / Online: 13 August 2021 (15:37:59 CEST)

How to cite: Ahmad, S.; Truran, S.; Karamanova, N.; Kindelin, A.; Lozoya, M.; Weissig, V.; Griffiths, D.; Vail, T.; Lifshitz, J.; Ducruet, A.F.; Migrino, R.Q. Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice. Preprints 2021, 2021080302 (doi: 10.20944/preprints202108.0302.v1). Ahmad, S.; Truran, S.; Karamanova, N.; Kindelin, A.; Lozoya, M.; Weissig, V.; Griffiths, D.; Vail, T.; Lifshitz, J.; Ducruet, A.F.; Migrino, R.Q. Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice. Preprints 2021, 2021080302 (doi: 10.20944/preprints202108.0302.v1).

Abstract

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) 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 score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

Keywords

stroke; liposome; cerebrovascular disease; oxidative stress; dementia

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