Mitochondrial biogenesis for the treatment of spinal cord injury

Spinal cord injury (SCI) is characterized by neuroinflammation, vascular disruption, ischemia, and disturbed mitochondrial homeostasis. The resulting mitochondrial dysfunction propagates loss of cellular functions, calcium overload, and oxidative stress, all of which contribute to neuronal cell death and functional impairments. Recent evidence supports pharmacological induction of mitochondrial biogenesis (MB) as an effective approach to decrease mitochondrial dysfunction and secondary injury progression. MB is a multifaceted process involving the integration of highly regulated transcriptional events, altered mitochondrial morphology and dynamics, lipid membrane and protein synthesis, and production of mitochondrial DNA. This chapter provides an overview of key aspects of mitochondrial dysfunction following SCI, and the impact of cell type-specific MB in neurons, endothelial cells, and astrocytes. Also discussed are studies documenting a variety of targets capable of MB induction, modulation of mitochondrial dysfunction, and pathological and functional improvements post-SCI.