Total Spinal Cord Transection Research Articles

Forced Remyelination Promotes Axon Regeneration in a Rat Model of Spinal Cord Injury

Spinal cord injuries result in the loss of motor and sensory functions controlled by neurons located at the site of the lesion and below. We hypothesized that experimentally enhanced remyelination supports axon preservation and/or growth in the total spinal cord transection in rats. Multifocal demyelination was induced by injection of ethidium bromide (EB), either at the time of transection or twice during transection and at 5 days post-injury. We demonstrated that the number of oligodendrocyte progenitor cells (OPCs) significantly increased 14 days after demyelination. Most OPCs differentiated into mature oligodendrocytes by 60-90 dpi in double-EB-injected rats; however, most axons were remyelinated by Schwann cells. A significant number of axons passed the injury epicenter and entered the distant segments of the spinal cord in the double-EB-injected rats. Moreover, some serotoninergic fibers, not detected in control animals, grew caudally through the injury site. Behavioral tests performed at 60-90 dpi revealed significant improvement in locomotor function recovery in double-EB-injected rats, which was impaired by the blockade of serotonin receptors, confirming the important role of restored serotonergic fibers in functional recovery. Our findings indicate that enhanced remyelination per se, without substantial inhibition of glial scar formation, is an important component of spinal cord injury regeneration.

Paraplegia, After Total Spinal Cord Transection in Mice

Mice, in contrast to other species, have the ability to recover after severe spinal cord damage without any therapeutic intervention. We studied the development of Wallerian degeneration of the long spinal tracts and also the contribution of proliferative neuronal and glial cells after complete spinal cord transaction including the dura matter in C57bl/6 mice. In addition, we monitored the functional recovery in association with histological and immunohistochemical observations. Critical point of time after SCT was the second week, when the lesion reached its maximum size, was well-vascularized and begun to self-limit drastically, thereafter. However, slight degree of functional recovery began from 48 hours after spinal cord transection. Immunophenotype analysis of the proliferative cells revealed that endogenous neurogenesis was of the glial, and not of the neuronal cell-type proliferation. Glial cells seemed to almost completely replace cellular loss, to remyelinate spared axons, to restore blood barrier and to support the rest, undamaged, neurons. Intense proliferation of glial cells occurred in the first 48 hours after injury and began to decline thereafter. Consequently, therapeutic interventions aiming at stimulation of endogenous neurogenesis should be initiated within the first hours after injury, while new approaches should target at stimulating not only the glial but also the endogenous neuronal cell-type proliferation.

Pain.

Pain has many valuable functions. It often signals injury or disease, generates a wide range of adaptive behaviors, and promotes healing through rest. Despite these beneficial aspects of pain, there are negative features that challenge our understanding of the puzzle of pain, including persistent phantom limb pain after amputation or total spinal cord transection. Pain is a personal, subjective experience influenced by cultural learning, the meaning of the situation, attention, and other psychological variables. Pain processes do not begin with the stimulation of receptors. Rather, injury or disease produces neural signals that enter an active nervous system that (in the adult organism) is the substrate of past experience, culture, and a host of other environmental and personal factors. These brain processes actively participate in the selection, abstraction, and synthesis of information from the total sensory input. Pain is not simply the end product of a linear sensory transmission system; it is a dynamic process that involves continuous interactions among complex ascending and descending systems. The neuromatrix theory guides us away from the Cartesian concept of pain as a sensation produced by injury, inflammation, or other tissue pathology and toward the concept of pain as a multidimensional experience produced by multiple influences. These influences range from the existing synaptic architecture of the neuromatrix-which is determined by genetic and sensory factors-to influences from within the body and from other areas in the brain. Genetic influences on synaptic architecture may determine-or predispose toward-the development of chronic pain syndromes. WIREs Cogn Sci 2013, 4:1-15. doi: 10.1002/wcs.1201 For further resources related to this article, please visit the WIREs website.

Time-related changes of motor unit properties in the rat medial gastrocnemius muscle after spinal cord injury. I. Effects of total spinal cord transection

The contractile properties of motor units (MUs) were electrophysiologically investigated in the medial gastrocnemius (MG) muscle in 17 Wistar three-month-old female rats: 14, 30, 90 and 180 days after the total transection of the thoracic spinal cord and compared to those in intact (control) rats. A sag phenomenon, regularly observed in unfused tetani of fast units in intact animals at 40 Hz stimulation, almost completely disappeared in spinal rats. Therefore, the MUs of intact and spinal rats were classified as fast or slow types basing on 20 Hz tetanus index, the value of which was lower or equal 2.0 for fast and higher than 2.0 for slow MUs. The MUs composition of MG muscle changed with time after the spinal cord transection: an increasing proportion of fast fatigable (FF) units starting one month after injury and a disappearance of slow (S) units within the three months were observed. In all MUs investigated the twitch contraction and half-relaxation time were significantly prolonged after injury ( p < 0.01, Mann–Whitney U-test). Moreover, a decrease of the fatigue index for fast resistant (FR) and slow MUs was observed in subsequent groups of spinal rats. No significant changes were found between twitch forces in all MU types of spinal animals ( p > 0.05). However, due to a decrease of the maximal tetanic force, a significant rise of the twitch-to-tetanus ratio of all MUs in spinal rats was detected ( p < 0.01). The considerable reduction of ability to potentiate the force was noticed for fast, especially FF type MUs. In conclusion, the spinal cord transection leads to changes in the proportion of the three MU types in rat MG muscle. The majority of changes in MUs’ contractile properties were developed progressively with time after the spinal cord injury. However, the most intensive alterations of twitch-time parameters were observed in rats one month after the transection.

Alexithymia and sense of coherence in patients with total spinal cord transection.

The study investigated the possibility that total spinal cord transection leading to tetraplegia would affect the ability to experience and identify emotions. It also examined whether the dispositional orientation of "sense of coherence" contributed to self-rated quality of life after spinal cord transection. Twenty patients with total spinal cord transection at the level of the sixth cervical vertebrae and 20 age- and sex-matched healthy control subjects completed measures of alexithymia, sense of coherence, and quality of life. There were no differences between the two groups on alexithymia scores. However, spinal injury patients reported significantly decreased quality of life relative to matched healthy control subjects. A strong sense of coherence was associated with better self-reported quality of life. This relationship remained after controlling for current affective status. We conclude that 1) loss of afferent feedback to the brain via the spinal cord does not have a significant effect on alexithymia scores, particularly factor 1 (difficulty in identifying feelings), and 2) sense of coherence may be an important factor in determining psychological adjustment after serious injury.

Altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity of cat lumbar motoneurons after chronic spinal cord transection

In cats subjected to total spinal cord transection at the lower thoracic level, the calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) was studied in motoneuron cell bodies in the L 6-L 7 segments. In transected animals, the CGRP-immunoreactive labeling of the motoneurons was virtually absent. When combining the spinal cord transection with a unilateral rhizotomy of all dorsal roots below the transection, however, an apparently normal labelling pattern of CGRP-LI of the motoneurons was displayed on both sides. Thus, surgical interventions which affect afferent pathways to the motoneurons may have influence on the levels of CGRP-LI in otherwise intact motoneurons.

Spinal pathways mediating respiratory influences on sympathetic nerves.

The location of spinal pathways mediating the respiratory modulation of sympathetic nerve activity was determined. Left inferior cardiac sympathetic, phrenic, and external intercostal (T1) nerve activities were recorded in 16 alpha-chloralose-anesthetized, vagotomized, paralyzed cats. Baroreceptor reflex activation of sympathetic activity was tested by bilateral carotid occlusion. Eight cats received C6-C7 level ventral spinal cord hemisections followed by cumulative lesions leading to total spinal cord transection. Eight other cats received C6-C7 level dorsolateral funiculus (DLF) lesions followed by dorsal spinal cord hemisection and subsequent spinal cord transection. The respiratory modulation of sympathetic activity was quantitatively assessed using respiration-triggered computer summation of sympathetic activity. Ventral hemisection had no significant effect on the respiratory modulation of sympathetic activity or bilateral carotid occlusion responses. In contrast, bilateral DLF lesions eliminated both the respiratory modulation and bilateral carotid occlusion responses. Unilateral disruption of DLF pathways ipsilateral to the recorded sympathetic nerve indicated spinal level decussations. Thus bilaterally descending DLF pathways with spinal level decussations mediate the respiratory modulation of sympathetic activity.

Immunocytochemical localization of substance P in the rat spinal cord with special reference to fibers within the ventral column of the rostral lumbar segments

The distribution of substance P (SP) in the rat spinal cord was investigated by peroxidase-anti-peroxidase (PAP) immunocytochemistry. A dense network of SP-immunoreactive fibers and terminals was detected in the ventral column of the rostral lumbar cord with a different density and extent from the other segmental levels. These fibers and terminals were accumulated within and around the centromedial nucleus (CM) of the L1 and L2 segments, with some bundles of immunoreactive fibers between the CM and other areas; i.e. laminae V and X and the contralateral CM. They formed a dense network, such as in arborization of immunoreactive fibers and terminals on the transverse plane and in a comb-shaped structure on the horizontal plane. The origin of the SP in this network was examined. It was determined that neither a total transection of spinal cord at a low thoracic level or mid-lumbar level, nor at an ipsilateral or bilateral section of the 3–5 dorsal roots, containing L1 and L2 roots, induced any visible changes in the SP staining pattern. An intrathecal injection of colchicine revealed the presence of SP-immunoreactive neurons in the dorsal horn and intermediate gray matter at the spinal cord including the rostral lumbar cord. The present findings suggested that the majority of SP immunoreactivities in the above network are derived from local circuit interneurons of the spinal cord.

The role of spinal pathways in dopamine mediated alteration in the tail-flick reflex in rats

The latency of the tail-flick, following intrathecal infusion of the dopamine (DA) agonist, R-apomorphine was measured in rats with intact spinal cord or with spinal cord lesions. Apomorphine failed to influence the tail-flick response in intact rats, whereas it elevated the latency of the tail-flick in rats with either total spinal cord transection, or bilateral lesions of the dorsolateral funiculi (DLF), but not in rats with lesions in either the dorsal columns or the medioventral parts of the lateral funiculi. The findings suggest that pathways in the dorsolateral funiculi modulate DA-mediated sensory processes and possible mechanisms are discussed.

Exaggeration of knee-jerk following spinal hemisection in monkeys

In 18 monkeys ipsilateral flaccid hemiplegia of the hind-limb was produced by spinal cord hemisection at T8. As a result of systematic observations of various phenomena subsequent to the hemisection for several months, it was found that an ipsilateral marked exaggeration of the knee-jerk gradually developed in 2--3 weeks after the infliction, along with slight atrophy of the hind-limb muscles on the same side. The exaggeration reached a maximum in about 6 weeks and persisted thereafter for several months until the final experiments. The exaggeration of knee-jerk was confirmed by measuring quantitatively photographed trajectories of a small lamp attached to the malleolus, a specially devised hammer being used. The trajectories showed larger amplitudes, shorter rise times and lower thresholds on the hemisected side. Achilles tendon reflex was also observed to be hyperactive. However, there was no evidence of other pathological phenomena such as clonus or Babinski's sign in the present experiment. It was noted that total spinal cord transection one segment below the hemisected site did not abolish the exaggeration of knee-jerk. Another noticeable finding was that quadriceps afferent volleys picked up from the L6 dorsal root following tendon taps were smaller on the hemisected side, in spite of the fact that distinct augmented reflex potentials were observed in the ipsilateral L6 ventral root. These results strongly suggest that the exaggeration of knee-jerk was not induced by a release from tonic supraspinal inhibition nor by augmented quadriceps afferent volleys, but by some neural mechanisms which developed gradually within the lumbo-sacral segments below the hemisected site.