Methylene blue and normobaric hyperoxia combination therapy in experimental ischemic stroke

Area of Science:

• Neuroscience
• Biomedical Engineering
• Pharmacology

Background:

• Ischemic stroke is a leading cause of disability and mortality worldwide.
• Current treatments for ischemic stroke have limitations in efficacy and accessibility.
• Developing novel therapeutic strategies is crucial for improving patient outcomes.

Purpose of the Study:

• To evaluate the efficacy of combined methylene blue (MB) and normobaric hyperoxia (NBO) therapy in an experimental model of ischemic stroke.
• To assess the impact of combined MB and NBO on infarct volume and sensorimotor functional recovery.
• To determine the long-term effects of the combined therapy up to 28 days post-stroke.

Main Methods:

• Transient middle cerebral artery occlusion (MCAO) was induced in rats.
• Animals were treated with air + vehicle, air + MB, NBO + vehicle, or NBO + MB.
• MB was administered multiple times post-stroke, and NBO was applied during MRI sessions.
• Serial MRI (diffusion, perfusion, T2) and behavioral tests (foot-fault, cylinder) were used to assess outcomes.

Main Results:

• Combined NBO + MB therapy demonstrated a greater reduction in infarct volume compared to NBO alone, and similar to MB alone.
• Sensorimotor functional recovery was accelerated in the NBO + MB group compared to NBO or MB monotherapy.
• While infarct volumes remained stable from day 2 to day 28, behavioral function continued to improve in the NBO + MB group.

Conclusions:

• Combined NBO + MB therapy offers a promising approach for improving functional outcomes in ischemic stroke.
• The synergistic effect of NBO and MB enhances infarct reduction and accelerates sensorimotor recovery.
• The observed improvements in functional recovery are sustained for at least 28 days, highlighting the long-term therapeutic potential.