Lasting paraplegia caused by loss of lumbar spinal cord interneurons in rats: no direct correlation with motor neuron loss

Object. The aims of this study were to investigate further the role played by lumbar spinal cord interneurons in the generation of locomotor activity and to develop a model of spinal cord injury suitable for testing neuron re placement strategies. Methods. Adult rats received intraspinal injections of kainic acid (KA). Lo comotion was assessed weekly for 4 weeks by using the Basso, Beattie, and B resnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor ev oked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscl es at 1 and 4 weeks. No changes in transcranial MMEP latency were noted fol lowing KA injection, indicating that the descending motor pathways responsi ble for these responses, including the alpha motor neurons, were not compro mised. Rats in which KA injections included much of the L-2 segment (10 ani mals) showed severe locomotor deficits, with a mean BBB score of 4.5 +/- 3. 6 (+/- standard deviation). Rats that received lesions rostral to the L-2 s egment (four animals) were able to locomote and had a mean BBB score of 14. 6 +/- 2.6. Three rats that received only one injection bilaterally centered at L-2 (three animals) had a mean BBB score of 3.2 +/- 2. Histological exa mination revealed variable loss of motor neurons limited to the injection s ite. There was no correlation between motor neuron loss and BBB score. Conclusions. Interneuron loss centered on the L-2 segment induces lasting p araplegia independent of motor neuron loss and white matter damage, support ing earlier suggestions that circuitry critical to the generator of locomot or activity (the central pattern generator) resides in this area. This inju ry model may prove ideal for studies of neuron replacement strategies.