Different Types of Nano Lipid Bubbles for Protecting Nerve Cells from Intermittent Hypoxia Damage.

Abstract

Intermittent hypoxia (IH) induced nerve cells apoptosis is an important cause of secondary cognitive dysfunction to obstructive sleep apnea (OSA) and may be a potential therapeutic target for this disease. This study was to explore the most appropriate conditions on the action of nano lipid bubbles (NLBs) which were applied to treat nerve injury caused by IH. An IH model of in vitro nerve cells was constructed. NLBs were created by reciprocating differential pressure method and magnetic xenon NLBs (Xe-NLBs) were created by magneto internal heat bubble generation (MIHBG). Morphology and stability of NLBs were tested via Transmission electron microscope (TEM) and dynamic light scatterer (DLS). Endocytosis and nerve injury after NLBs treatment were assessed by Immunofluorescence and MTT assay. Both Xe-NLBs (10⁷ bubbles/ml, prepared by the reciprocal differential pressure method) and magnetic Xe-NLBs (10⁷ bubbles/ml, prepared by the MIHBG) administration for up to 6 h after IH onset reduced IH induced nerve injury, and the magnetic Xe-NLBs showed a better neuroprotection, whereas O₂, H₂, and N₂-NLBs did not show significant effects. An equal volume of saturated xenon aqueous solution (Xe-solution) exhibited similar results although these therapeutic effects were far less than those of magnetic Xe-NLBs. These results revealed that Xe was the most effective neuroprotective gas in IH-induced nerve injury. Xe-NLBs prepared by the MIHBG have achieved the maximal therapeutic effects by 10⁷ bubbles/ml with 6 h treatment time under IH.