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Sci Rep. 2018 Oct 9;8(1):15041. doi: 10.1038/s41598-018-33296-z.

Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia.

Author information

1
Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea.
2
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA.
3
Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.
4
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA. priti.kumar@yale.edu.
5
Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul, Korea. sangkyunglee@hanyang.ac.kr.

Abstract

Ischemic stroke-induced neuronal cell death results in the permanent disabling of brain function. Apoptotic mechanisms are thought to play a prominent role in neuronal injury and ample evidence implicates Fas signaling in mediating cell death. In this study, we describe the neuroprotective effects of a Fas-blocking peptide (FBP) that by obstructing Fas signaling in cerebral ischemia inhibits apoptosis. Using an intranasal administration route in a rat model of focal cerebral ischemia, we demonstrate that nose-to-brain delivery of FBP after middle cerebral artery occlusion (MCAO) surgery results in the delivery and retention of FBP in Fas-expressing ischemic areas of the brain. A single intranasal administration of 2 mg/kg FBP resulted in significantly reduced neuronal cell death by inhibiting Fas-mediated apoptosis leading to decreased infarct volumes, reduced neurologic deficit scores and recovery from cerebral ischemia. Intranasally delivered FBP might be a promising strategy for the treatment of cerebral ischemic stroke.

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