Therapeutic utility of Perfluorocarbon Oxygent in limiting the severity of subarachnoid hemorrhage in mice

Sci Rep. 2024 Nov 4;14(1):26638. doi: 10.1038/s41598-024-77321-w.

Abstract

Subarachnoid hemorrhage (SAH) is the deadliest form of hemorrhagic stroke; however, effective therapies are still lacking. Perfluorocarbons (PFCs) are lipid emulsion particles with great flexibility and their much smaller size as compared to red blood cells (RBCs) allows them to flow more efficiently within the blood circulation. Due to their ability to carry oxygen, a specific PFC-based emulsion, PFC-Oxygent, has been used as a blood substitute; however, its role in cerebral blood flow regulation is unknown. Adult C57BL/6 wildtype male mice were subjected to an endovascular perforation model of SAH followed by an intravenous (i.v.) injection of 9 ml/kg PFC-Oxygent or no treatment at 5 h after SAH. At 48 h after SAH, functional and anatomical outcomes were assessed. We found that SAH resulted in significant neurologic and motor deficits which were prevented by PFC-Oxygent treatment. We found that SAH-induced vasospasm, reduced RBC deformability, and augmented endothelial dysfunction were also restricted by PFC-Oxygent treatment. Moreover, mitochondrial activity and fusion proteins were also markedly decreased as assessed by oxidative phosphorylation (OXPHOS) after SAH. Interestingly, PFC-Oxygent treatment brought the mitochondrial activity close to the basal level. Moreover, SAH attenuated the level of phosphorylated AMP-activated protein kinase (pAMPK), whereas PFC treatment improved pAMPK levels. These data show the beneficial effects of PFC-Oxygent in limiting the severity of SAH. Further studies are needed to fully understand the mechanism through which PFC-Oxygent exerts its beneficial effects in limiting SAH severity.

Keywords: Cerebral blood flow; Hemorrhagic stroke; Neurological deficits; Perfluorocarbon; Red blood cell deformability; Vasospasm.

MeSH terms

  • Animals
  • Blood Substitutes / pharmacology
  • Cerebrovascular Circulation / drug effects
  • Disease Models, Animal*
  • Fluorocarbons* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Phosphorylation / drug effects
  • Oxygen / metabolism
  • Subarachnoid Hemorrhage* / complications
  • Subarachnoid Hemorrhage* / drug therapy
  • Subarachnoid Hemorrhage* / metabolism
  • Vasospasm, Intracranial / drug therapy
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / metabolism

Substances

  • Fluorocarbons
  • Blood Substitutes
  • Oxygen