TY - JOUR T1 - Mitochondrial-based therapeutics for the treatment of spinal cord injury: mitochondrial biogenesis as a potential pharmacological target JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.117.244806 SP - jpet.117.244806 AU - Natalie E Scholpa AU - Rick G. Schnellmann Y1 - 2017/01/01 UR - http://jpet.aspetjournals.org/content/early/2017/09/21/jpet.117.244806.abstract N2 - Spinal cord injury (SCI) is characterized by an initial trauma followed by a progressive cascade of damage referred to as secondary injury. A hallmark of secondary injury is vascular disruption leading to vasoconstriction and decreased oxygen delivery, directly reducing the ability of mitochondria to maintain homeostasis, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, further exacerbating injury. Restoration of mitochondria dysfunction during the acute phases of secondary injury post-SCI represents a potentially effective therapeutic strategy. This review discusses the past and present pharmacological options for the treatment of SCI, as well as current research on mitochondria-targeted approaches. Increased antioxidant activity, inhibition of the mitochondrial permeability transition, alternate energy sources and manipulating mitochondrial morphology are among the strategies under investigation. Unfortunately, many of these tactics address single aspects of mitochondrial dysfunction, ultimately proving largely ineffective. Therefore, this review will also examine the unexplored therapeutic efficacy of pharmacological enhancement of mitochondrial biogenesis, which has the potential to more comprehensively improve mitochondrial function following SCI. ER -