Motor neuron degeneration after sciatic nerve avulsion in adult rat evolves with oxidative stress and is apoptosis

The mechanisms for motor neuron degeneration and regeneration in adult spin al cord following axotomy and target deprivation are not fully understood, We used a unilateral sciatic nerve avulsion model in adult rats to test the hypothesis that retrograde degeneration of motor neurons resembles apoptos is, By 21 days postlesion, the number of large motor neurons in lumbar spin al cord was reduced by similar to 30%, The death of motor neurons was confi rmed using the terminal transferase-mediated deoxyuridine triphosphate-biot in nick-end labeling method for detecting fragmentation of nuclear DNA, Mot or neuron degeneration was characterized by aberrant accumulation of perika ryal phosphorylated neurofilaments. Structurally, motor neuron death was ap optosis, Apoptotic motor neurons undergo chromatolysis followed by progress ive cytoplasmic and nuclear condensation with chromatin compaction into uni formly large round clumps. Prior to apoptosis, functionally active mitochon dria accumulate within chromatolytic motor neurons, as determined by cytoch rome c oxidase activity. These dying motor neurons sustain oxidative damage to proteins and nucleic acids within the first 7 days after injury during the progression of apoptosis, as identified by immunodetection of nitrotyro sine and hydroxyl-modified deoxyguanosine and guanosine, We conclude that t he retrograde death of motor neurons in the adult spinal cord after sciatic nerve avulsion is apoptosis, Accumulation of active mitochondria within th e perikaryon and oxidative damage to nucleic acids and proteins may contrib ute to the mechanisms for apoptosis of motor neurons in the adult spinal co rd. (C) 1999 John Wiley & Sons, Inc.