Monosialoganglioside-Containing Nanoliposomes Protect Against Acute and Chronic Ischemic Stroke Injury

Neuroprotective strategies as primary or ancillary treatment could ameliorate the significant mortality and disability associated with ischemic stroke. Nanoliposomes composed of monosialoganglioside, phosphatidylcholine, and cholesterol (NLGM1) were previously shown to ameliorate brain injury when given before arterial occlusion in mice. We aimed to test the hypothesis that NLGM1 given following transient intraluminal filament and photothrombotic (PT) middle cerebral artery occlusion (MCAO) will attenuate acute and chronic stroke injury in mice.

Twelve-week-old C57BL/6 mice underwent MCAO for 45 minutes and were then injected with 1 or 3 doses of saline or NLGM1 (1 or 2 mg IV) after occlusion. Neurologic deficit score and brain infarct area were measured after 48 hours. Separate mice underwent PT occlusion of the distal lateral middle cerebral artery trunk followed by injection of 1 or 2 doses saline or NLGM1 (1 or 2 mg IV) postocclusion. Motor and behavior testing was performed at 21, 30, 45, and 90 days after PT MCAO.

Following intraluminal MCAO, single-dose NLGM1-treated mice exhibited reduced neurological impairment (neurologic deficit score 3.6±0.2, 2.6±0.3, 2.4±0.3 at 0, 1, 2 mg, respectively; P<0.05 versus control) and reduced infarct area (29.8±2.9%, 15.0±1.5%, 13.0±1.2%; P<0.001 versus control) with similar results with multiple dosing. Following PT MCAO, day 21 latency to fall (rotarod test), day 30 corner test, day 45 adhesive tape removal, and day 90 novel object recognition were improved in single-dose NLGM1-treated mice versus controls with improved corner and adhesive tape removal tests with multiple dosing. There were no significant differences in outcomes between 1 versus 2 mg NLGM1 treatments.

Treatment of mice with NLGM1 resulted in reduced brain infarct size acutely following intraluminal MCAO and improved motor and behavior function acutely and chronically following intraluminal and PT MCAO. NLGM1 represents a promising novel neuroprotective agent in stroke.