Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose cellular homeostasis and can lead to eventual cell death. Targeting of mitochondrial dysfunction in various diseases has proven a successful approach, lending support to mitochondria as a pivotal player in TBI cell death and loss of behavioral function.
Within this mixed mini review/research article there will be a general discussion of mitochondrial bioenergetics, followed by a brief discussion of traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. We will also give an overview of one relatively new TBI therapeutic approach, Methylene Blue, currently being studied to ameliorate mitochondrial dysfunction following brain injury. We will also present novel experimental findings, that for the first time, characterize the ex vivo effect of Methylene Blue on mitochondrial function in synaptic and non-synaptic populations of mitochondria.
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Kentucky Spinal Cord and Head Injury Research Trust #15-14A (PGS), part of this work was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117 (PGS). This work was supported in part by a Merit Review Award # I01BX003405 to (PGS) from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program. This work is also supported in part by a NIH/NIA K01 Mentored Career Development Award (K01AG040164) to (A-LL).
Vekaria, Hemendra J.; Talley Watts, Lora; Lin, Ai-Ling; and Sullivan, Patrick G., "Targeting Mitochondrial Dysfunction in CNS Injury Using Methylene Blue; Still a Magic Bullet?" (2017). Spinal Cord and Brain Injury Research Center Faculty Publications. 29.