Mitochondrial dysfunction as a target in spinal cord injury:intimate correlation between pathological processes and therapeutic approaches  

作　　者：Julieta Schmidt Héctor Ramiro Quintá 

机构地区：[1]Universidad de Buenos Aires,CABA,Argentina [2]Laboratorio de Medicina Experimental“Dr.J.Toblli”,Hospital Alemán,CABA,Argentina [3]Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET,CABA,Argentina [4]Rehabilitation Medicine Department,University of Minnesota,Twin Cities,MIN,USA

出　　处：《Neural Regeneration Research》2023年第10期2161-2166,共6页中国神经再生研究（英文版）

基　　金：supported by a grant from PICT2019-N°01665 to HRQ

摘　　要：Traumatic spinal cord injuries interrupt the connection of all axonal projections with their neuronal targets below and above the lesion site. This interruption results in either temporary or permanent alterations in the locomotor, sensory, and autonomic functions. Damage in the spinal tissue prevents the re-growth of severed axons across the lesion and their reconnection with neuronal targets. Therefore, the absence of spontaneous repair leads to sustained impairment in voluntary control of movement below the injury. For decades, axonal regeneration and reconnection have been considered the opitome of spinal cord injury repair with the goal being the repair of the damaged long motor and sensory tracts in a complex process that involves:(1) resealing injured axons;(2) reconstructing the cytoskeletal structure inside axons;(3) re-establishing healthy growth cones;and(4) assembling axonal cargos. These biological processes require an efficient production of adenosine triphosphate, which is affected by mitochondrial dysfunction after spinal cord injury. From a pathological standpoint, during the secondary stage of spinal cord injury, mitochondrial homeostasis is disrupted, mainly in the distal segments of severed axons. This result in a reduction of adenosine triphosphate levels and subsequent inactivation of adenosine triphosphate-dependent ion pumps required for the regulation of ion concentrations and reuptake of neurotransmitters, such as glutamate. The consequences are calcium overload, reactive oxygen species formation, and excitotoxicity. These events are intimately related to the activation of necrotic and apoptotic cell death programs, and further exacerbate the secondary stage of the injury, being a hallmark of spinal cord injury. This is why restoring mitochondrial function during the early stage of secondary injury could represent a potentially effective therapeutic intervention to overcome the motor and sensory failure produced by spinal cord injury. This review discusses the most recent evidence linkin

关 键 词：adenosine triphosphate axonal regeneration CREATINE mitochondria dysfunction MITOCHONDRIA spinal cord injury 

分 类 号：R651[医药卫生—外科学]