Constructing Mg-Based Hydrogen Container for Mitochondrial Dysfunction and Neuronal Ferroptosis in TCAR-Induced...

Area of Science:

• Neuroscience
• Biomedical Engineering
• Materials Science

Background:

• Cerebral ischemia/reperfusion injury (CIRI) involves mitochondrial dysfunction and reactive oxygen species (ROS) overexpression, leading to neuronal ferroptosis.
• The blood-brain barrier (BBB) hinders effective delivery of therapeutics, including hydrogen (H2), into the brain.
• Sustainable and high-dose H2 delivery for treating brain conditions remains a challenge.

Purpose of the Study:

• To develop an innovative method for H2 administration to overcome BBB limitations.
• To investigate the therapeutic potential of MgH2 microparticles in a novel CIRI rabbit model.
• To elucidate the mechanisms by which MgH2 treatment mitigates neuronal ferroptosis and restores mitochondrial function in CIRI.

Main Methods:

• Developed intraperitoneal injection of magnesium hydride (MgH2) microparticles for sustained H2 release.
• Established a novel CIRI rabbit model using transcarotid artery revascularization (TCAR).
• Assessed the effects of MgH2 treatment on ROS levels, ferroptosis markers, mitochondrial membrane potential, mitobiogenesis, energy metabolism, and anti-oxidative pathways.

Main Results:

• MgH2 microparticles achieved persistent, high-dose H2 supply to the blood and brain.
• MgH2 treatment effectively eliminated intracellular ROS and inhibited neuronal ferroptosis in the CIRI model.
• Restored mitochondrial dysfunction by stabilizing membrane potential, regulating mitobiogenesis, enhancing energy metabolism, and activating anti-oxidative pathways.

Conclusions:

• MgH2 microparticle injection is a promising strategy for sustained H2 delivery to the brain.
• This method shows significant therapeutic potential for treating CIRI by combating oxidative stress and ferroptosis.
• MgH2 treatment offers a new avenue for managing neurological damage caused by ischemia/reperfusion injury.