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


METHODS
Adult rats received intraspinal injections of kainic acid (KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and 4 weeks. No changes in transcranial MMEP latency were noted following KA injection, indicating that the descending motor pathways responsible for these responses, including the alpha motor neurons, were not compromised. Rats in which KA injections included much of the L-2 segment (10 animals) 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 segment (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 examination revealed variable loss of motor neurons limited to the injection site. There was no correlation between motor neuron loss and BBB score.


CONCLUSIONS
Interneuron loss centered on the L-2 segment induces lasting paraplegia independent of motor neuron loss and white matter damage, supporting earlier suggestions that circuitry critical to the generator of locomotor activity (the central pattern generator) resides in this area. This injury model may prove ideal for studies of neuron replacement strategies.
Hadi
B
B
Department of Neurological Surgery, University of Louisville School of Medicine, Kentucky 40202, USA.
Zhang
Y P
YP
Burke
D A
DA
Shields
C B
CB
Magnuson
D S
DS
D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D004594:Electrophysiology; D007395:Interneurons / Q000473:pathology / Q000502:physiology*; D008159:Lumbar Vertebrae; D008297:Male; D009043:Motor Activity; D009045:Motor Endplate / Q000503:physiopathology; D009046:Motor Neurons / Q000473:pathology; D010264:Paraplegia / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013118:Spinal Cord Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*