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Updated: Aug 29, 2025

Non-thermal Infrared Light Treatment of Ischemia/Reperfusion Injury and Subsequent Analysis of Macrophage Differentiation
Published on: December 30, 2021
Sometimes less is more: inhibitory infrared light during early reperfusion calms hyperactive mitochondria and
Paul T Morse1, Junmei Wan1, Jamie Bell1,2
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, U.S.A.
Abstract:
Ischemic stroke affects over 77 million people annually around the globe. Due to the blockage of a blood vessel caused by a stroke, brain tissue becomes ischemic. While prompt restoration of blood flow is necessary to save brain tissue, it also causes reperfusion injury. Mitochondria play a crucial role in early ischemia-reperfusion injury due to the generation of reactive oxygen species (ROS). During ischemia, mitochondria sense energy depletion and futilely attempt to up-regulate energy production. When reperfusion occurs, mitochondria become hyperactive and produce large amounts of ROS which damages neuronal tissue. This ROS burst damages mitochondria and the cell, which results in an eventual decrease in mitochondrial activity and pushes the fate of the cell toward death. This review covers the relationship between the mitochondrial membrane potential (ΔΨm) and ROS production. We also discuss physiological mechanisms that couple mitochondrial energy production to cellular energy demand, focusing on serine 47 dephosphorylation of cytochrome c (Cytc) in the brain during ischemia, which contributes to ischemia-reperfusion injury. Finally, we discuss the use of near infrared light (IRL) to treat stroke. IRL can both stimulate or inhibit mitochondrial activity depending on the wavelength. We emphasize that the use of the correct wavelength is crucial for outcome: inhibitory IRL, applied early during reperfusion, can prevent the ROS burst from occurring, thus preserving neurological tissue.
Insights
Ischemic stroke causes brain damage through mitochondrial reactive oxygen species (ROS) production during reperfusion. Inhibitory near-infrared light therapy can prevent this ROS burst, preserving neurological tissue.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Ischemic stroke leads to brain tissue damage due to blocked blood flow and subsequent reperfusion injury.
- Mitochondria are key players in ischemia-reperfusion injury, generating damaging reactive oxygen species (ROS) upon reperfusion.
- The review examines the link between mitochondrial membrane potential and ROS generation, and cellular energy regulation.
Approach:
- Discusses the role of serine 47 dephosphorylation of cytochrome c (Cytc) in the brain during ischemia.
- Explores how mitochondria attempt to up-regulate energy production during ischemia, leading to hyperactivity and ROS bursts upon reperfusion.
- Reviews the therapeutic potential of near-infrared light (IRL) for stroke treatment.
Key Points:
- Mitochondrial hyperactivity and excessive ROS production during reperfusion cause significant neuronal damage.
- Dysregulation of mitochondrial energy production and cytochrome c activity contribute to stroke-induced injury.
- Near-infrared light (IRL) can modulate mitochondrial activity, with specific wavelengths offering therapeutic benefits.
Conclusions:
- Targeting mitochondrial ROS production during the early reperfusion phase is critical for mitigating stroke damage.
- Understanding the interplay between mitochondrial function and cellular energy demand is essential for developing effective stroke therapies.
- Optimized IRL therapy, applied early in reperfusion, shows promise in preventing ROS bursts and preserving brain tissue after ischemic stroke.

