Delivery of xenon-containing echogenic liposomes inhibits early brain injury following subarachnoid hemorrhage

Sci Rep. 2018 Jan 11;8(1):450. doi: 10.1038/s41598-017-18914-6.

Abstract

Xenon (Xe), a noble gas, has promising neuroprotective properties with no proven adverse side-effects. We evaluated neuroprotective effects of Xe delivered by Xe-containing echogenic liposomes (Xe-ELIP) via ultrasound-controlled cerebral drug release on early brain injury following subarachnoid hemorrhage (SAH). The Xe-ELIP structure was evaluated by ultrasound imaging, electron microscopy and gas chromatography-mass spectroscopy. Animals were randomly divided into five groups: Sham, SAH, SAH treated with Xe-ELIP, empty ELIP, or Xe-saturated saline. Treatments were administrated intravenously in combination with ultrasound application over the common carotid artery to trigger Xe release from circulating Xe-ELIP. Hematoma development was graded by SAH scaling and quantitated by a colorimetric method. Neurological evaluation and motor behavioral tests were conducted for three days following SAH injury. Ultrasound imaging and electron microscopy demonstrated that Xe-ELIP have a unique two-compartment structure, which allows a two-stage Xe release profile. Xe-ELIP treatment effectively reduced bleeding, improved general neurological function, and alleviated motor function damage in association with reduced apoptotic neuronal death and decreased mortality. Xe-ELIP alleviated early SAH brain injury by inhibiting neuronal death and bleeding. This novel approach provides a noninvasive strategy of therapeutic gas delivery for SAH treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravenous
  • Animals
  • Brain Injuries / diagnostic imaging
  • Brain Injuries / drug therapy*
  • Brain Injuries / etiology
  • Disease Models, Animal
  • Drug Liberation
  • Liposomes / administration & dosage
  • Liposomes / chemistry
  • Microscopy, Electron, Transmission
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacokinetics
  • Random Allocation
  • Rats
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / diagnostic imaging
  • Subarachnoid Hemorrhage / drug therapy*
  • Ultrasonography
  • Xenon / administration & dosage*
  • Xenon / pharmacokinetics

Substances

  • Liposomes
  • Neuroprotective Agents
  • Xenon