Effects of spinal transection in neonatal and weanling rats: Survival of function

doi:10.1016/0014-4886(75)90039-4

Experimental Neurology

Volume 46, Issue 1, January 1975, Pages 156-177

https://doi.org/10.1016/0014-4886(75)90039-4 Get rights and content

Abstract

The spinal cord of neonatal rats and weanling rats was transected midthoracically. The recovery and maturation of responses in the hind quarters were followed and compared with response development in normal rats. In rats transected as neonates, the hind limbs supported the hind quarters, the tail was dorsiflexed, and the hind limbs stepped during locomotion. When a hind limb fell through a grid, struggling movements, replacement, and a response similar to tactile placing were observed. Rapid extension often bounced the hind quarters off a grid when the foot pads contacted a grid bar. Pinching elicited clonic flexion and wriggling of the hind quarters with a prolonged afterdischarge. In animals transected as weanlings, the hind limbs and tail were passively extended and did not participate in locomotion. The hind limbs also hung passively through a grid and struggling was brief. Clonic flexion and wriggling to pinch lacked an afterdischarge. Choreoathetoidlike movements and spasms were common in the weanling group. In a number of respects including temporal correspondence in the appearance of certain responses, the response maturation of the neonatally transected animal resembled the ontogeny of responses in the normal animal. These data indicate that the local development of the spinal cord continues in the absence of supraspinal control. Hence it appears that the presence or absence of supraspinal control during development is the basis for the differences in the survival of responses from the isolated spinal cords of the neonatal group when compared to the weanling animals. This “survival of function” effect may help to explain the sparing of function often found after lesions in the developing nervous system.

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Postural control is critical for locomotion, allowing for gait changes, obstacle avoidance and navigation of rough terrain. A major problem after spinal cord injury (SCI) is regaining the control of balance to prevent falls and further injury. While the circuits for locomotor pattern generation reside in the spinal cord, postural control consists of multiple, complex networks that interact at the spinal, brainstem and cortical levels. After complete SCI, cortical reorganization establishes novel control of trunk musculature that is required for weight-supported stepping. In this study, we examined the impact of exercise therapy on cortical reorganization in the more clinically relevant models of both moderate and severe midthoracic contusion injury in the rat. Results demonstrate that both spontaneous recovery and therapy induced recovery of weight-supported stepping utilize cortical reorganization. Moreover, exercise therapy further improves outcome by enhancing cortical control of lower thoracic muscles enabling improvements in interlimb coordination associated with improved balance that increases weight-supported stepping. The outcome of this study suggest that cortical control of posture is key to functional improvement in locomotion. This information can be used to improve the timing and type of therapy after SCI by considering changes along the entire neural axis.
Chondroitin sulfate expression around motoneurons changes after complete spinal transection of neonatal rats
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Hind limb locomotor activity spontaneously recovers after complete spinal transection (CST) in neonatal rats, but the mechanisms underlying the recovery are poorly understood. The perineuronal net (PNN) surrounding the neuronal cell bodies comprises an extracellular matrix that regulates neuronal plasticity during development. Here, we examined the expression of chondroitin sulfate (CS), a major component of the PNN, on motoneurons after CST in neonatal rats, and compared it with that in juvenile rats, in which hindlimb locomotor activity does not recover spontaneously.
The spinal cord was transected at the mid-thoracic level in neonatal (postnatal day 5 [P5] and P10) and juvenile (P15 and P20) rats. Two weeks after CST, the percentage of motoneurons surrounded by chondroitin sulfate C (CS-C) − positive structures was significantly lower in rats with CST at P10 than in intact rats, and tended to be higher in rats with CST at P15 than in intact rats. The percentage of motoneurons with CS-A − positive structures was significantly lower in rats with CST at P15 than in intact rats.
These findings suggest that CS-A and CS-C are differentially expressed in the PNNs in rats with CST. The decrease in CS-C − positive PNNs might facilitate the formation of new synaptic contacts to motoneurons, resulting in the recovery of the hindlimb locomotor activity in rats with CST during the neonatal period.
Neonatal spinal injury induces de novo projections of primary afferents to the lumbosacral intermediolateral nucleus in rats
2018, IBRO Reports
Citation Excerpt :
Severe dysuria in rodents with complete SCI is usually managed by researchers manually pressing on the urinary bladder twice a day (Herrera et al., 2010). Rats that undergo spinal cord transection at the neonatal period, however, exhibit far less motor dysfunction compared to those at the adult stage (Stelzner et al., 1975; Yuan et al., 2013; Takiguchi et al., 2015). We recently demonstrated that compensatory projections of primary afferent fibers to the intermediate zone and the ventral horn in the lumbar spinal segment are strengthened after neonatal spinal cord transection at the thoracic level, based on experiments in which biotinylated dextran amine (BDA), an anterograde tracer, was administered into the dorsal root ganglion (DRG) (Takiguchi et al., 2015).
Complete spinal transection in adult rats results in poor recovery of hind limb function and severe urinary bladder dysfunction. Neonatal rats with spinal cord transection, however, exhibit spontaneous and significant recovery of micturition control. A previous study in which biotinylated-dextran amine (BDA) was used as an anterograde tracer demonstrated that primary afferent fibers from the fifth lumbar dorsal root ganglion (DRG) project more strongly and make more terminals in the ventral horn after neonatal spinal cord transection at the mid-thoracic level. In the present study, we injected BDA into the sixth lumbar (L6) DRG of neonatally spinalized rats to label primary afferent fibers that include visceral afferents. The labeled fibers projected to the intermediolateral nucleus (IML) in the intermediate zone on ipsilateral side of the L6 spinal segment, whereas no projections to the IML were observed in sham-operated or intact rats. The BDA-labeled fibers of neonatally spinalized rats formed varicose terminals on parasympathetic preganglionic neurons in the IML. These findings suggest that some primary afferent projections from the L6 DRG to the IML appear after neonatal spinal cord transection, and these de novo projections might contribute to the recovery of autonomic function such as micturition following spinal cord injury in the neonatal stage.
Compensatory projections of primary sensory fibers in lumbar spinal cord after neonatal thoracic spinal transection in rats
2015, Neuroscience
Complete spinal transection in adult rats results in poor recovery of hind limb function, whereas significant spontaneous recovery can occur following spinal cord transection in rat neonates. The mechanisms underlying the recovery, however, are poorly understood. Recent studies in rodents suggested that the recovery is not due to axonal regeneration, but rather due to reorganization of the neural circuits in the spinal cord below the injury site, including central pattern generators. Few studies have reported histological evidence for changes in the primary sensory fibers or terminals. Thus, in the present study, we transected spinal cords of rats at thoracic level 8 at postnatal day 5. Four weeks after the injury, biotinylated-dextran amine (BDA), an anterograde tracer, was injected into the dorsal root ganglion of the lumbar spinal cord to examine the localization of sensory fibers and their terminal buttons in the spinal cord. BDA-positive axons in the rat spinal cord following neonatal spinal transection (neo ST) were longer than those in sham-operated or normal rats. The number of terminal buttons was also higher in spinal cords of neo ST rats compared with sham-operated or normal rats. These findings suggest that sensory fibers project more strongly and make more synapses following neo ST to compensate for the lack of supraspinal projections.
Plasticity of motor network and function in the absence of corticospinal projection
2015, Experimental Neurology
Citation Excerpt :
Motor control is also partly restored by a reorganization of spinal intrinsic networks. After the spinal cord section, spontaneous walking recovers, mainly thanks to changes of intrinsic circuitry (Anderson et al., 2007; Bareyre et al., 2004; Courtine et al., 2009; Stelzner et al., 1975; Tillakaratne et al., 2010). Propriospinal neurons, which send axons to different spinal segments (Flynn et al., 2011) and are important for the modulation of skilled movements (Azim et al., 2014), can create new intraspinal circuits that bypass injury sites and relay cortical inputs to their original targets (Deng et al., 2013).
Despite the obvious clinical interest, our understanding of how developmental mechanisms are redeployed during degeneration and regeneration after brain and spinal cord injuries remains quite rudimentary. In animal models of spinal cord injury, although spontaneous regeneration of descending axons is limited, compensation by intact corticospinal axons, descending tracts from the brainstem, and local intrinsic spinal networks all contribute to the recovery of motor function. Here, we investigated spontaneous motor compensation and plasticity that occur in the absence of corticospinal tract, using Celsr3|Emx1 mice in which the corticospinal tract is completely and specifically absent as a consequence of Celsr3 inactivation in the cortex. Mutant mice had no paresis, but displayed hyperactivity in open-field, and a reduction in skilled movements in food pellet manipulation tests. The number of spinal motoneurons was reduced and their terminal arbors at neuromuscular junctions were atrophic, which was reflected in electromyography deficits. Rubrospinal projections, calretinin-positive propriospinal projections, afferent innervation of motoneurons by calretinin-positive segmental interneurons, and terminal ramifications of monoaminergic projections were significantly increased. Contrary to control animals, mutants also developed a severe and persistent disability of forelimb use following the section of the rubrospinal tract at the C4 spinal level. These observations demonstrate for the first time that the congenital absence of the corticospinal tract induces spontaneous plasticity, both at the level of the motor spinal cord and in descending monoaminergic and rubrospinal projections. Such compensatory mechanisms could be recruited in case of brain or spinal cord lesion or degeneration.
Neurochemical excitation of thoracic propriospinal neurons improves hindlimb stepping in adult rats with spinal cord lesions
2015, Experimental Neurology
Using an in vitro neonatal rat brainstem–spinal cord preparation, we previously showed that cervicothoracic propriospinal neurons contribute to descending transmission of the bulbospinal locomotor command signal, and neurochemical excitation of these neurons facilitates signal propagation. The present study examined the relevance of these observations to adult rats in vivo. The first aim was to determine the extent to which rats are able to spontaneously recover hindlimb locomotor function in the presence of staggered contralateral hemisections (left T2–4 and right T9–11) designed to abolish all long direct bulbospinal projections. The second aim was to determine whether neurochemical excitation of thoracic propriospinal neurons in such animals facilitates hindlimb stepping. In the absence of intrathecal drug injection, all animals (n = 24) displayed some degree of hindlimb recovery ranging from weak ankle movements to brief periods of unsupported hindlimb stepping on the treadmill. The effect of boluses of neurochemicals delivered via an intrathecal catheter (tip placed midway between the rostral and caudal thoracic hemisections) was examined at post-lesion weeks 3, 6 and 9. Quipazine was particularly effective facilitating hindlimb stepping. Subsequent complete transection above the rostral (n = 3) or caudal (n = 2) hemisections at week 9 had no consistent effect on drug-free locomotor performance, but the facilitatory effect of drug injection decreased in 4/5 animals. Two animals underwent complete transection at T3 as the first and only surgery and implantation of two intrathecal catheters targeted to the mid-thoracic and lumbar regions, respectively. A similar facilitatory effect on stepping was observed in response to drugs administered via either catheter. The results indicate that partial spontaneous recovery of stepping occurs in adult rats after abolishing all long direct bulbospinal connections, in contrast to previous studies suggesting that hindlimb stepping after dual hemisections either does not occur or is observed only if the second hemisection surgery is delayed relative to the first. The results support the hypothesis that artificial modulation of propriospinal neuron excitability may facilitate recovery of motor function after spinal cord injury. However, whether this facilitation is due to enhanced transmission of a descending locomotor signal or is the result of excitation of thoracolumbar circuits independent of supraspinal influence, requires further study.

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¹: We would like to thank Dr. Donald C. Goodman and Dr. James A. Horel for helpful criticism on the content of this manuscript. We would also like to thank Mr. Brian Goodman for help with the testing of animals and Ms. Judith Strauss for histological assistance. Supported by Grant NS-10579.

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Effects of spinal transection in neonatal and weanling rats: Survival of function

Abstract

Exp. Neurol.

Exp. Neurol.

Anim. Behav.

Brain Res.

Exp. Neurol.

Exp. Neurol.

Brain Res.

Speed, accuracy and strength of forelimb movement after unilateral pyramidotomy in rhesus monkeys

J. Comp. Physiol. Psychol.

Modification of Gudden method for study of cerebral localization

Arch. Neurol. Psychiat.

Effects of various cortical lesions on development of placing and hopping reactions in rats

J. Neurophysiol.

Structural regeneration in the mammalian central nervous system in relation to age

Anatomical and physiological correlates of plasticity in the central nervous system

Brain Behav. Evol.

Restitution of function in the CNS: the pathological grasp in Macaca mulatta

Exp. Brain Res.

Evidence for behavioral impairment following prefrontal lobectomy in the infant monkey

J. Comp. Physiol. Psychol.