The development and recovery of motor function in spinal cats

Abstract

The effects of the gamma-aminobutyric acid (GABA) antagonist bicuculline (BCC) on hindlimb motor performance was examined in mature spinal cats with spinal cord transections made either on the day of birth or at approximately two weeks postpartum and in chronic adult cats with spinal transections made in adulthood. In those adult operates, whose pre-drug performance was poor compared to neonatal operates, treadmill locomotion and weight support were improved dramatically by BCC administration. In neonatal operates (examined as adults), BCC administration increased the force of extension to abnormal levels and this increase appeared to disrupt locomotion. Immunocytochemical localization of GABA's synthetic enzyme, glutamic acid decarboxylase (GAD) within the spinal cords of these animals revealed an abnormal distribution of GAD reaction product only in newborn operates. The behavioral results indicate that the full extent of recovery in adult operates is prevented by inhibitory influences and this may contribute to the comparatively superior performance of neonatal operates i.e., the infant lesion effect. The anatomical results suggest that one requirement for the normal development of some intrinsic spinal circuitry is transneuronal regulation mediated by the maturation of descending systems.

Overexpression of BDNF Increases Excitability of the Lumbar Spinal Network and Leads to Robust Early Locomotor Recovery in Completely Spinalized Rats

“…These findings strongly suggest a decrease of inhibition in the rostral, and, to a lesser extent, in the caudal segments in spinal animals and question the proposition that glycinergic and GABAergic inhibition is increased in the caudal lumbar segments [6], [19], [83] contributing to an overall depression of hindlimb movements [21]. The discrepancy between our data and those of others may be related to the time period after transection and species [6], [83].…”

“…In adult chronic spinal rats less GABAergic inhibition than in acute spinal rats was reported [20]. In adult spinal cats, an increase of GABA-mediated inhibition in the lumbar spinal circuits [21] and of GABA synthesizing enzyme glutamate decarboxylase 67 (GAD67) levels [6] were observed. A prevailing view thus emerged that in adult animals spinal cord injury leads to a loss of balance between excitatory and inhibitory systems that leads to inappropriate locomotion [22].…”

Weight-Bearing Locomotion in the Developing Opossum, Monodelphis domestica following Spinal Transection: Remodeling of Neuronal Circuits Caudal to Lesion

“…An increase in GABA synthesis following spinal injury has been shown in cats [54] and an increase in GABA-A receptor subunits in certain motoneurons following injury in the rat has been observed [55]. Administration of GABA receptor blockers [57] or glycine receptor blockers [58] resulted in improved stance and locomotion suggesting that the inhibitory GABA- or glycinergic systems in the spinal cord interfere with locomotor generation. Similar increases in the amount of glycine receptor have been shown in the lumbar spinal cords of rats following spinal injury [56], similar to the P7-injured opossums.…”

Adaptations in Glutamate and Glycine Content within the Lumbar Spinal Cord Are Associated with the Generation of Novel Gait Patterns in Rats following Neonatal Spinal Cord Transection

“…It is well known that neonatal spinally transected animals recovered better hindlimb function than the adult transected animals (Weber and Stelzner, 1977). After spinal cord transection in adults, inhibition in the lumbar spinal circuits increased above normal and this contributed to an overall depression of hindlimb movements (Robinson and Goldberger, 1986). In contrast, the level of excitation within the lumbar spinal circuitry rose after a spinal cord transection was performed in neonatal rats (Norreel et al, 2003).…”