Congenital kyphoscoliosis and spinal cord lesion produced in the rat by beta-aminopropionitrile

Pregnant rats received the lathyrogen beta-aminopropionitrile (1,500 mg/kg) intraperitoneally on day 16 (plug day = 0 day). Kyphoscoliosis was produced in a high incidence in the fetuses at the level of the upper thoracic spine as early as 24 hours after treatment. Although most of the affected newborns died within two weeks, survivors were studied until 20 weeks after birth. Survivors developed paraplegia in consequence of kyphoscoliosis. Both spinal deformity and motor disturbance were progressive. Biochemical and electron microscopic observations suggested that beta-aminopropionitrile treatment resulted in an inhibition of collagen formation in the spinal column and surrounding longitudinal ligaments of the fetuses six hours after the treatment. In addition, electron micrographs of vertebral bodies showed a decrease of proteoglycan granules in the extracellular matrix. Therefore, rupture and collapse of weakened ligaments and vertebral bodies might result in severe spinal deformity and spinal cord lesion.     

Excessive reflexes in spinal cord injury triggered by electrical stimulation

Interaction of electrocutaneous stimulation with an impaired human motor control system may result in unstable reflex loops causing excessive spastic reactions. These contractions are usually excluded from analysis since the presence of spasm is one of the criteria commonly applied for discarding a contraction. They may, however, provide interesting information on the nature of spasticity. The dorsiflexor muscles of four SCI subjects were activated by means of surface electrical stimulation and the isometric ankle moment was measured. Short bursts of constant stimulation frequency at seven different frequencies (8, 12, 16, 20, 25, 33, 50 Hz) triggered spastic reactions in all subjects. The onset times of spastic activity during an electrically elicited contraction shortened with increased stimulation frequency. A stimulation burst may also have a spasticity reduction effect on a subsequent burst, indicating potential short term therapeutic effects of stimulation on spasticity in isometric conditions.     

Physiologic evidence for descending tryptaminergic pathways in the spinal cord.

LSD was more effective in facilitating the flexor reflex in the chronic than in the acute spinal dog. On the other hand, $\text{1}$-tryptophan produced a significant facilitation of the flexor reflex in the acute spinal dog but not in the chronic spinal dog. These data are consistent with the hypothesis that there are long descending tryptaminergic axons which have the capacity of converting tryptophan to tryptamine and releasing it in the vicinity of post-synaptic facilitatory receptors which degenerate in the chronic spinal dog.     

Stabilization of intracellular recordings in the cat spinal cord using high-frequency ventilation

Stabilization of intracellular recordings by a substantial reduction of respiratory motion may be accomplished by the use of high-frequency ventilation (600-800 breaths/min). The technique is a simple one and enables maintenance of relatively constant blood gas tensions. Although the improved stability was demonstrated in experiments performed on alpha motoneurones in the thoracic spinal cord, it is anticipated that a reduced respiratory movement should benefit recordings in other spinal and supraspinal sites.     

Descending modulation of reflex reactions in spinal motoneurons produced by spinal cord injury in man

A study was made of changes in the amplitude of H-reflexes in m. gastrocnemius and the intensity of Ia inhibition in healthy subjects versus patients with midthoracic injury to the spinal cord before, during, and after voluntary tensing of the masticatory, cervical, and finger muscles. Tensing these muscles brought about facilitation of H-reflex and reduced intensity of Ia response in healthy subjects and patients with paraparesis but produced the opposite effect on paraplegics (or had no influence on reactions). This leads to a discussion of the relationship between the changes observed in reflex reactions and posttrauma damage to structure and function of the spinal cord.A. A. Bogomolets Institute, of Physiology, Academy of Sciences of the Ukrainian SSR. Kiev. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 105–113, January–February, 1988.     

Extrapyramidal descending influences on neurons of the spinal cord in a superreflexia state

The spinal superreflexia state was modeled in experiments on rats using preliminary transection of the spinal cord and injection (in the course of the acute experiment) of 4-aminopyridine. An extremely high (reaching 15–20 mV) amplitude of monosynaptic reflex discharges (MRs) evoked by stimulation of the dorsal root and recorded from the ventral root (VR) L ₄ and the presence of an additional component in the above discharges were phenomena indicative of the development of the above state. Under such conditions, the amplitudes of the discharges evoked in the VR by electrical stimulation of the round window of the labyrinth (vestibular stimulation) and of the discharges elicited by stimulation of the motor cortex under conditions of bilateral transection of the pyramids increased several times. Thresholds of the VR responses to vestibular and cortical stimulations demonstrated an about threefold drop; latencies of the mass responses and responses of single spinal moto-and interneurons decreased about twofold, on average. The pattern of vestibular conditioning effects on the VR MRs changed: in intact animals vestibular stimulation induced inhibition of the VR MRs, while in animals with superreflexia such stimulation led to facilitation of the MRs. Cortical stimulation under conditions of pyramidotomy in both intact animals and animals with superreflexia resulted in facilitation of the VR MRs of a nearly the same intensity. The levels of convergence of the segmental and supraspinal effects on interneurons and motoneurons of the rat spinal cord dramatically increased under superreflexia conditions. The possible mechanisms of augmentation of the descending influences on spinal neuronal systems under the above conditions are discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 2, pp. 140–149, March–April, 2006.     

Dissociate destruction of noradrenaline and dopamine descending projections in the thoracic spinal cord of the rat

Intracisternal administration of 6-hydroxydopamine to male Wistar rats produced a near complete depletion of noradrenaline levels, as measured by a radioenzymatic assay in micropunches sampled from the dorsal, lateral and ventral horns of the thoracic spinal cord. This drastic effect was reversed by pretreatment with desipramine, a pharmacological inhibitor of noradrenergic neuron uptake. Surprisingly, dopamine content was not significantly reduced. The question as to whether such a lack of concomitant dopamine decrease might be inherent to the dopamine assay itself could be answered by the results obtained with both pharmacological (reserpine) treatments and interference determinations in the dopamine assay. The relative potency of 6-hydroxydopamine to destroy noradrenergic and dopaminergic neurons might account for their differential behavior. Conversely, a large midbrain section performed by knife cut could decrease both dopamine and DOPAC (one of its major acid metabolites) in the thoracic lateral horn and partly in the ventral one. The noradrenaline content was not reduced. Results are discussed in light of recently reported data on dopaminergic descending projections to the spinal cord. The lesion procedures presented here seem to provide valuable tools to dissociate noradrenergic from dopaminergic spinal projections, which is necessary for further anatomical and functional studies on these systems.     

Laminar distribution of sources of ascending spinocerebral fiber systems in the cat spinal cord

The location of labeled neurons that are sources of ascending crossed and uncrossed supraspinal fiber systems was studied in the laminae of gray matter of the spinal cord in 18 cats by the retrograde axonal transport of horseradish peroxidase method. Neurons in the lateral zones of the dorsal horn were shown to make direct, and cells in neighboring regions indirect (through relay nuclei of the dorsal columns) connections with the contralateral thalamus. In the lower segments of the spinal cord sources of crossed spinoreticular and spinothalamic fiber systems are located in the medial regions of the ventral horn and lateral zones of the lateral basilar region. Some large neurons in the motor nuclei were shown to send their axons into the lateral reticular nucleus of the medulla. On the basis of the results a scheme of the laminar organization of sources of ascending fiber systems in the cat spinal cord is constructed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 5, pp. 451–459, September–October, 1979.     

Retinoic acid-dependent signaling pathways and lineage events in the developing mouse spinal cord

Studies in avian models have demonstrated an involvement of retinoid signaling in early neural tube patterning. The roles of this signaling pathway at later stages of spinal cord development are only partly characterized. Here we use Raldh2-null mouse mutants rescued from early embryonic lethality to study the consequences of lack of endogenous retinoic acid (RA) in the differentiating spinal cord. Mid-gestation RA deficiency produces prominent structural and molecular deficiencies in dorsal regions of the spinal cord. While targets of Wnt signaling in the dorsal neuronal lineage are unaltered, reductions in Fibroblast Growth Factor (FGF) and Notch signaling are clearly observed. We further provide evidence that endogenous RA is capable of driving stem cell differentiation. Raldh2 deficiency results in a decreased number of spinal cord derived neurospheres, which exhibit a reduced differentiation potential. Raldh2-null neurospheres have a decreased number of cells expressing the neuronal marker β-III-tubulin, while the nestin-positive cell population is increased. Hence, in vivo retinoid deficiency impaired neural stem cell growth. We propose that RA has separable functions in the developing spinal cord to (i) maintain high levels of FGF and Notch signaling and (ii) drive stem cell differentiation, thus restricting both the numbers and the pluripotent character of neural stem cells.