Therapeutic Time Window and Dose Dependence of Xenon Delivered via Echogenic Liposomes for Neuroprotection in Stroke

CNS Neuroscience and Therapeutics - Tập 19 Số 10 - Trang 773-784 - 2013
Christy K. Holland1, George Britton1, Hyunggun Kim1, Davide Cattano2, Jaroslaw Aronowski3, James C. Grotta3, David D. McPherson1, Shao‐Ling Huang1
1Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
2Department of Anesthesiology, University of Texas Health Science Center at Houston, Houston, TX, USA
3Department of Neurology, University of Texas Health Science Center at Houston Houston, TX, USA.

Tóm tắt

SummaryAimsNeurologic impairment following ischemic injury complicates the quality of life for stroke survivors. Xenon (Xe) has favorable neuroprotective properties to modify stroke. Xe delivery is hampered by a lack of suitable administration strategies. We have developed Xe‐containing echogenic liposomes (Xe‐ELIP) for systemic Xe delivery. We investigated the time window for Xe‐ELIP therapeutic effect and the most efficacious dose for neuroprotection. Molecular mechanisms for Xe neuroprotection were investigated.MethodsXenon‐containing echogenic liposomes were created by a previously developed pressurization‐freezing method. Following right middle cerebral artery occlusion (2 h), animals were treated with Xe‐ELIP at 2, 3, or 5 h to determine time window of therapeutic effect. The neuroprotectant dosage for optimal effect was evaluated 3 h after stroke onset. Expression of brain‐derived neurotrophic factor (BDNF), protein kinase B (Akt), and mitogen‐activated protein kinases (MAPK) was determined.ResultsXenon‐containing echogenic liposomes administration for up to 5 h after stroke onset reduced infract size. Treatment groups given 7 and 14 mg/kg of Xe‐ELIP reduced infarct size. Behavioral outcomes corresponded to changes in infarct volume. Xe‐ELIP treatment reduced ischemic neuronal cell death via activation of both MAPK and Akt. Elevated BDNF expression was shown following Xe‐ELIP delivery.ConclusionThis study demonstrates the therapeutic efficacy of Xe‐ELIP administered within 5 h after stroke onset with an optimal dosage range of 7–14 mg/kg for maximal neuroprotection.

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CNS Neuroscience and Therapeutics

Tập 19 Số 10

773-784

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