Abstract
BackgroundTraumatic injury to the central nervous system results in damage to tissue beyond the primary injury, termed secondary degeneration. Key events thought to be associated with secondary degeneration involve aspects of mitochondrial function which may be modulated by red/near-infrared irradiation therapy (R/NIR-IT), but precisely how mitochondria are affected in vivo has not been investigated. Secondary degeneration was modelled by transecting the dorsal aspect of the optic nerve in adult rats and mitochondrial ultrastructure in intact ventral optic nerve vulnerable to secondary degeneration investigated with transmission electron microscopy.ResultsDespite reported increases in fission following central nervous system injury, we saw no change in mitochondrial densities in optic nerve vulnerable to secondary degeneration in vivo. However, in axons, frequency distributions of mitochondrial profile areas showed higher cumulative probabilities of smaller mitochondrial profiles at day 1 after injury. Glial mitochondrial profiles did not exhibit changes in area, but a more elliptical mitochondrial shape was observed at both day 1 and 7 following injury. Importantly, mitochondrial autophagic profiles were observed at days 1 and 7 in optic nerve vulnerable to secondary degeneration in vivo. Citrate synthase activity was used as an additional measure of mitochondrial mass in ventral optic nerve and was decreased at day 7, whereas mitochondrial aconitase activity increased at day 1 and day 28 after injury in optic nerve vulnerable to secondary degeneration. R/NIR-IT has been used to treat the injured central nervous system, with reported improvements in oxidative metabolism suggesting mitochondrial involvement, but ultrastructural information is lacking. Here we show that R/NIR-IT of injured animals resulted in distributions of mitochondrial areas and shape not significantly different from control and significantly reduced mitochondrial autophagic profiles. R/NIR-IT also resulted in decreased citrate synthase activity (day 7) and increased aconitase activity (day 1) in optic nerve vulnerable to secondary degeneration.ConclusionsThese findings suggest that mitochondrial structure and activity of enzymes of the citric acid cycle are dynamically altered during secondary degeneration in vivo and R/NIR-IT may protect mitochondrial structure.
Highlights
Traumatic injury to the central nervous system results in damage to tissue beyond the primary injury, termed secondary degeneration
Density of mitochondrial profiles did not change in areas of optic nerve (ON) vulnerable to secondary degeneration +/− R/NIR-IT Mitochondria can respond to stress in part by altering the balance between fission and fusion [15]
We assessed mitochondrial profiles at 1 and 7 days after injury, as we have already demonstrated that the oxidative stress response is well established at 1 day [1] and mitochondrial ultrastructure changes as a response to oxidative stress may be beginning to resolve at 7 days
Summary
Traumatic injury to the central nervous system results in damage to tissue beyond the primary injury, termed secondary degeneration. Key events thought to be associated with secondary degeneration involve aspects of mitochondrial function which may be modulated by red/near-infrared irradiation therapy (R/NIR-IT), but precisely how mitochondria are affected in vivo has not been investigated. Acute injury to the central nervous system (CNS) is associated with secondary degeneration involving both neurons and glia neighbouring the lesion, resulting in further functional loss [1,2]. Ca2+ concentrations are disturbed both at and adjacent to the injury [4], and mitochondria take up excess Ca2+. Mitochondria are a major source of reactive oxygen species (ROS), the production of which is increased with elevated mitochondrial Ca2+ concentrations [7]. We have previously demonstrated both altered Ca2+ distributions and oxidative stress in white matter vulnerable to secondary degeneration [8]
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