Structural changes of anterior horn neurons and their synaptic input caudal to a low thoracic spinal cord hemisection in the adult rat: a light and electron microscopic study

Abstract

Structural changes in lumbosacral ventral horn neurons and their synaptic input were studied at 3, 10, 21, 42, and 90 days following low thoracic cord hemisection in adult rats by light microscopic examination of synaptophysin immunoreactivity (SYN-IR) and by electron microscopy. There was an ipsilateral transient decrease in SYN-IR at the somal and proximal dendritic surfaces of anterior horn neurons which extended caudally from the site of injury over a postoperative (p.o.) period of 42 days. Concomitantly, at 21 days p.o., perineuronal SYN-IR started to recover in upper lumbar segments. By 90 days p.o., a normal staining pattern of SYN was noted in upper and mid lumbar segments, but the perineuronal SYN-IR was still slightly below normal levels in low lumbar and sacral segments. Electron microscopy revealed ultrastructural changes coincident with the alterations in SYN-IR. At 3 days p.o., phagocytosis of degenerating axon terminals by activated microglial cells was observed at the somal and proximal dendritic surfaces of ventral horn neurons. These changes were most prominent up to two segments caudal to the lesion. At 10 days p.o., advanced stages of bouton phagocytosis were still detectable in all lumbosacral motor nuclei. Additionally, abnormal axon terminals, with a few dispersed synaptic vesicles and accumulations of large mitochondria, appeared at the scalloped somal surfaces of anterior horn neurons. At 21 days p.o., several large lumbosacral motoneurons had developed chromatolysis-like ultrastructural alterations and motoneuronal cell bodies had become partially covered by astrocytic lamellae. At 42 days p.o., there was a transient appearance of polyribosomes in some M-type boutons. In addition, at 42 and 90 days p.o., a few degenerating motoneurons were detected in all lumbosacral segments, but most displayed normal neuronal cell bodies contacted by numerous intact synapses as well as by astrocytic processes. In contrast to these striking alterations of synaptic input at somal and proximal dendritic surfaces of motoneurons, relatively few degenerating boutons were detected in the neuropil of motor nuclei at all the p.o. times studied. We suggest that the preferential disturbance of the predominantly inhibitory axosomatic synapses on ventral horn neurons may be involved in the mechanisms which influence the well-established increase in motoneuronal excitability after spinal cord injury.

Tenascin-R Restricts Posttraumatic Remodeling of Motoneuron Innervation and Functional Recovery after Spinal Cord Injury in Adult Mice

“…The abnormalities found in the intact spinal cord may contribute to motor impairments of TNR Ϫ/Ϫ mice that become apparent under demanding conditions, such as rotarod, pole, and wirehanging tests (Freitag et al, 2003), but are not detectable in less stressful and challenging tests as those used here for analysis of motor functions. Previous studies have shown that spinal cord injury causes an acute loss of motoneuron perisomatic terminals, which is gradually reversed in chronic paraplegic rats (Nacimiento et al, 1995). In wild-type mice studied 6 weeks after injury, densities of GABAergic terminals were similar to intact mice, suggesting that this local input is not changed after injury or is normalized during the recovery period.…”

Step Training-Dependent Plasticity in Spinal Cutaneous Pathways

“…These studies indicate that physiological, biochemical, and functional reorganization of lumbar spinal cord occur over time (Nacimiento et al, 1995;Edgerton et al, 1997a,b;Giroux et al, 1999). Consistent with this, strategies to recover motor functions after spinal cord injury (SCI) include the management of sublesional spinal cord based on the reorganization of the remaining undamaged neural pathways.…”

Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

“…47,48 We performed a systematic analysis of the immunostaining for synaptophysin in the cervical spinal cord (C4-C8) as a first step in characterizing the synaptic changes that occur in the partially denervated segments. Our objective was to investigate the possibility that synaptic loss persisted chronically in the spinal cord segments adjacent to the lesion site and, hence, we quantified the intensity of staining in a group of normal rats (n = 8) and two groups of rats with C6 hemisection, at 30 (n = 12) or 90 (n = 12) DPI.…”