Hindlimb Weight Support Research Articles

Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord.

Transplantation approaches using cellular bridges, fetal central nervous system cells, fibroblasts expressing neurotrophin-3 (ref. 6), hybridoma cells expressing inhibitory protein-blocking antibodies, or olfactory nerves ensheathing glial cells transplanted into the acutely injured spinal cord have produced axonal regrowth or functional benefits. Transplants of rat or cat fetal spinal cord tissue into the chronically injured cord survive and integrate with the host cord, and may be associated with some functional improvements. In addition, rats transplanted with fetal spinal cord cells have shown improvements in some gait parameters, and the delayed transplantation of fetal raphe cells can enhance reflexes. We transplanted neural differentiated mouse embryonic stem cells into a rat spinal cord 9 days after traumatic injury. Histological analysis 2-5 weeks later showed that transplant-derived cells survived and differentiated into astrocytes, oligodendrocytes and neurons, and migrated as far as 8 mm away from the lesion edge. Furthermore, gait analysis demonstrated that transplanted rats showed hindlimb weight support and partial hindlimb coordination not found in 'sham-operated' controls or control rats transplanted with adult mouse neocortical cells.

NMDA antagonism during development extends sparing of hindlimb function to older spinally transected rats

Hindlimb weight support and bipedal stepping occur after spinal cord transection in neonatal rats (birth to 12 days of age) while the same lesion in 15-day and older animals results in permanent loss of these responses. Some compensatory change in lumbar spinal circuitry must occur after spinal transection in young animals subserving these hindlimb behaviors. In contrast, animals just a few days older are incapable of such compensatory responses. We have examined the hypothesis that neural activity leads to the postnatal loss of plasticity in spinal circuitry. We find that antagonism of the N-methyl- d-aspartate (NMDA) subtype of glutamate receptor with MK-801 in young animals extends the sparing of hindlimb function after spinal transection to older animals. This effect is not due to a non-specific depression of all exciatory drive to motor neurons since Ia to motor neuron synaptic transmission through non-NMDA receptors is preserved during MK-801 treatment. Acute administration of MK-801 at the time of spinal transection or chronic administration of MK-801 after postnatal day 17 has no effect on recovery of hindlimb function after spinal transection. These results highlight the importance of NMDA receptor activation in spinal circuit maturation.

Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. II. Stepping in spinal kittens

From birth to postnatal day 60, neuromuscular patterns for airstepping and treadmill stepping were assessed in kittens spinalized (T12) at birth (Day-1) or at the end of the second postnatal week (Day-14). Within 72 h after spinalization, all kittens displayed stepping motions, but exteroceptive facilitation (e.g. tail pinch) was required to initiate and sustain both behaviors. In Day-14 spinal kittens, the hindlimbs spontaneously and alternately airstepped, but in Day-1 spinal kittens exteroceptive stimulation was usually necessary to evoke airstepping, and the hindlimbs stepped synchronously. Kittens in both groups developed atypical neuromuscular patterns; flexor bursts were nearly twice as long in duration as extensor bursts. Development of bipedal treadmill stepping was similar for Day-1 and Day-14 spinal kittens, but differed from that for normal kittens9. Tested at the same belt speeds, stepping was more easily elicited in spinal kittens, bouts of repetitive stepping were longer, and cycle periods were shorter than in normal kittens until postnatal week 6. Spinal kittens, however, seldom exhibited adequate weight support during hindlimbs stepping, and the neuromuscular patterns associated with bipedal stepping were atypical. For spinal kittens, the relationship between the extensor burst duration and the cycle period was reduced substantially, and flexor activity was initiated earlier in the step cycle and was longer in duration than that for normal kittens. These atypical intralimb synergies may have been the consequence of altered lumbosacral circuits produced by the spinal transection. It is also possible that these spinal circuits, lacking rostral input, were particularly susceptible to abnormal motion-dependent feedback resulting from reduced hindlimb weight support.