Delayed Pathophysiology of Mild Traumatic Brain Injury: the Diminished Role of Ca2+ Buffering Capacity of Cerebral Mitochondria

Abstract

Mitochondrial dysfunction is shown to be associated with many diseases, such as neurodegeneration, diabetes, cardiomyopathy or developmental delay, etc. Energy generation in the mitochondria meets the demands and is extremely specific to different tissues. The brain is rather small (1-2% of body weight) in relation to the whole body, but it consumes ten times more oxygen and glucose than any other tissue. Oxygen is consumed predominantly in the mitochondria, in the electron transport chain (ETC) in a process that is coupled to the production of ATP. Singlet oxygen is the electronically excited state of molecular oxygen (lowest excited state of the dioxygen molecule) which is less stable than molecular oxygen in the electronic ground state. Singlet oxygen is largely accepted to be a highly damaging radical that is made use of in the photodynamic therapy of cancer (PDT), always in the presence of photosensitizers. Here, we report for the first time we report positive effects of singlet oxygen, specific to the mitochondrial energy metabolism. We have found that illumination of primary co-culture of neurons and astrocytes with laser which wavelength that coincides with one of the highest absorption peaks of the oxygen molecule, produces high level of singlet oxygen inside the cells. We have also found that this type of laser irradiation increases mitochondrial membrane potential, stimulates NADH-and FADH-dependent respiration and significantly increases the efficiency of oxidative phosphorylation. Finally, this results in an increase in the ATP levels in mitochondria of neurons and astrocytes. It should be noted that these effects are dependent on the irradiation dose and an increase of the dose over a certain threshold lead to toxic effects.