Tail spasms in rat spinal cord injury: Changes in interneuronal connectivity

Uncontrolled muscle spasms often develop after spinal cord injury. Structural and functional maladaptive changes in spinal neuronal circuits below the lesion site were postulated as an underlying mechanism but remain to be demonstrated in detail. To further explore the background of such secondary phenomena, rats received a complete sacral spinal cord transection at S2 spinal level. Animals progressively developed signs of tail spasms starting 1 week after injury. Immunohistochemistry was performed on S3/4 spinal cord sections from intact rats and animals were sacrificed 1, 4 and 12 weeks after injury.We found a progressive decrease of cholinergic input onto motoneuron somata starting 1 week post-lesion succeeded by shrinkage of the cholinergic interneuron cell bodies located around the central canal. The number of inhibitory GABAergic boutons in close contact with Ia afferent fibers was greatly reduced at 1 week after injury, potentially leading to a loss of inhibitory control of the Ia stretch reflex pathways. In addition, a gradual loss and shrinkage of GAD65 positive GABAergic cell bodies was detected in the medial portion of the spinal cord gray matter. These results show that major structural changes occur in the connectivity of the sacral spinal cord interneuronal circuits below the level of transection. They may contribute in an important way to the development of spastic symptoms after spinal cord injury, while reduced cholinergic input on motoneurons is assumed to result in the rapid exhaustion of the central drive required for the performance of locomotor movements in animals and humans.

► Rats with complete sacral spinal cord transection developed tail spasms.
► Below the injury site, cholinergic input on motoneurons was decreased.
► The number of GABAergic boutons on Ia afferents was reduced.
► Spinal cholinergic and GABAergic interneuron cell bodies showed atrophy.
► These structural changes could lead to spastic symptoms after spinal cord injury.