Effects Of Spinal Cord Transection Research Articles

Different effects of spinalization and locomotor training of spinal animals on cholinergic innervation of the soleus and tibialis anterior motoneurons

Cholinergic input modulates excitability of motoneurons and plays an important role in the control of locomotion in both intact and spinalized animals. However, spinal cord transection in adult rats affects cholinergic innervation of only some hindlimb motoneurons, suggesting that specificity of this response is related to functional differences between motoneurons. Our aim was therefore to compare cholinergic input to motoneurons innervating the soleus (Sol) and tibialis anterior (TA) motoneurons following spinal cord transection at a low-thoracic level. The second aim was to investigate whether deficits in cholinergic input to these motoneurons could be modified by locomotor training. The Sol and TA motoneurons were identified by retrograde labelling with fluorescent dyes injected intramuscularly. Cholinergic terminals were detected using anti-vesicular acetylcholine transporter (VAChT) antibody. Overall innervation of motoneurons was evaluated with anti-synaptophysin antibody. After spinalization we found a decrease in the number of VAChT-positive boutons apposing perikarya of the Sol (to 49%) but not TA motoneurons. Locomotor training, resulting in moderate functional improvement, partly reduced the deficit in cholinergic innervation of Sol motoneurons by increasing the number of VAChT-positive boutons. However, the optical density of VAChT-positive boutons terminating on various motoneurons, which decreased after spinalization, continued to decrease despite the training, suggesting an impairment of acetylcholine availability in the terminals. Different effects of spinal cord transection on cholinergic innervation of motoneurons controlling the ankle extensor and flexor muscles point to different functional states of these muscles in paraplegia as a possible source of activity-dependent signaling regulating cholinergic input to the motoneurons.

Sarco(endo)plasmic reticulum calcium pump isoforms in paralyzed rat slow muscle

To assess the influence of paralysis on the expression of phenotypic protein isoforms related to muscle relaxation, the effects of spinal cord transection (ST) on sarco(endo)plasmic reticulum calcium ATPase (SERCA) pump isoform protein levels in the slow rat soleus were measured. Western blotting using SERCA isoform specific antibodies demonstrated a rapid up-regulation (7 days post ST) of the fast fiber type-specific isoform (SERCA1). In contrast, the slow fiber type-specific isoform, SERCA2, was decreased with a slower time-course. The up-regulation of SERCA1 protein preceded the up-regulation of fast myosin heavy chain (MyHC) (i.e., MyHC-II). Immunohistochemical analyses of single muscle fibers showed that 15 days after ST there was a pronounced increase in the proportion of slow MyHC fibers with SERCA1 confirming that SERCA1 was up-regulated in the slow fibers of the soleus prior to MyHC-II. These data suggest that the expression of the SERCA isoforms (particularly SERCA1) may serve as more sensitive markers of phenotypic adaptation in response to altered levels of contractile activity than the MyHC isoforms. In addition, since the expression of SERCA isoforms was dissociated from MyHC isoforms, regulation of gene expression for these two different protein systems must involve different signaling events and/or synthetic processes.

Early effects of spinal cord transection on skeletal muscle properties

Modulation of beta-adrenergic receptor (beta-AR) activity affects muscle mass and could have a role in the reduction of muscle mass observed following spinal cord transection (Tx). The aims of this study were to examine the early acute effects of Tx on muscle mass, total and myofibrillar protein concentrations, cytochrome c oxidase activity, and beta-AR density of skeletal muscle, to ascertain if any change in muscle properties could be related to beta-AR signalling events. Female Sprague-Dawley rats (n = 33; approximately 255 g) were randomly assigned to 4 experimental groups: control 4 d, control 8 d, Tx 4 d, and Tx 8 d. A complete Tx was performed surgically at the T10 cord level. Compared with controls, muscle mass and muscle - body mass ratios decreased significantly following Tx, with no significant change observed in total and myofibrillar protein concentrations. Spinal cord Tx also resulted in a significant decrease in plantaris cytochrome c oxidase activity by 24% at Tx 4 d and 28% at Tx 8 d (p < 0.05). Beta-AR density of the lateral gastrocnemius was unchanged; however, the beta-AR density of the forelimb triceps brachii m. was found to increase after Tx. Our results suggest that changes in muscle mass and cytochrome c oxidase activity rapidly occur after Tx and do not appear to be related to changes in beta-AR density.

Effect of neonatal spinal transection and dorsal rhizotomy on hindlimb muscles

The purpose of this study was to elucidate the effect of deafferentation on spinal motoneurons. We studied the effects of spinal cord transection and/or dorsal rhizotomy upon the contractile properties of EDL and soleus muscle, as well as on the number of motoneurons corresponding to these muscles. Neonatal Wistar rats were randomly divided into four groups in which spinal midthoracic section (T8–T10), unilateral dorsal lumbar rhizotomy (L3–S2) or both procedures were performed on the second postnatal day (PND2). Another group served as unoperated control. At 2 months of age, the animals were evaluated for the contractile properties of a fast (EDL) and a slow (soleus) muscle. Isometric tension recordings were elicited by way of sciatic nerve branches stimulation. In addition, the incremental method was applied for the determination of the number of motor units supplying the two muscles, which was also verified by using the horseradish peroxidase (HRP) method of reverse labeling of motoneurons. Muscle alterations were confirmed by the usual biochemical staining. Our results, in agreement with the data from other researchers, show that significant muscle atrophy takes place after all experimental procedures. Additionally, spinal cord section alters the development of the dynamic properties of soleus muscle, which attains a fast profile. Following transection, the number of motor units remained unaltered, while rhizotomy affected only the soleus by reducing its motor units. The combined procedure affected both muscles, indicating that adequate synaptic input is essential for motoneuron survival.

Myosin heavy chain isoform mRNA and protein levels after long-term paralysis

To assess the long-term influence of paralysis on muscle phenotypic mRNA and protein expression, the effects of spinal cord transection (ST) on myosin heavy chain (MyHC) isoform mRNA and protein levels in the soleus and medial gastrocnemius (MG) muscles of rats were analyzed. Control soleus contained predominantly MyHC-I with low amounts of MyHC-IIa and IIx mRNAs. After ST, MyHC-I mRNA decreased to ∼15%, MyHC-IIa was increased by 75–200%, and MyHC-IIx was elevated by 8–10×. Low level expression of MyHC-IIb was observed post-ST, suggesting that reduced activity is not a primary stimulus for MyHC-IIb expression. Adaptations in mRNA preceded protein adaptations in the soleus. Although MyHC-I protein in the MG was reduced post-ST, no other consistent changes occurred. The relative lack of adaptation to ST by the MG suggests that the reduced activity and load bearing encountered by the MG were insufficient to induce a change in muscle phenotype.

Evidence For a Central Pathway in the Cerebrovascular Effects Of Spinal Cord Stimulation

Cervical spinal cord stimulation (SCS) augments cerebral blood flow (CBF) in a number of animal models. The mechanisms underlying the cerebrovascular effects of SCS are not yet well delineated. In this study, we analyzed two alternative pathways in CBF alterations induced by SCS in rats, one involving direct modulation of sympathetic outflow and the other through central vasomotor influence. Resection of the superior cervical ganglion (SCG), SCS alone, or SCS after SCG removal was performed in adult male Sprague-Dawley rats. CBF was measured with (14)C-inosine monophosphate radiotracer studies. In another set of experiments, SCS was performed after spinalization at the cervicomedullary junction or after laminectomy alone. Baseline CBF in the SCG removal group was 71 +/- 8 ml/100 g/min, similar to controls. SCS alone significantly increased blood flow to 100 +/- 10 ml/100 g/min (P < 0.05). Animals that underwent SCS after SCG removal demonstrated a similar robust augmentation in CBF. SCS-induced changes in CBF were completely attenuated by spinalization. The profound effects of spinal cord transection on SCS-induced CBF augmentation, together with the lack of effect of surgical sympathectomy, suggest that the mechanisms underlying the effects of SCS involve central influences rather than cervical sympathetic outflow. These findings suggest a possible role for brainstem vasomotor centers in the cerebrovascular effects of SCS.

Retraining the injured spinal cord.

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

Effect of spinal cord transection on N-methyl-D-aspartate receptors in the cord.

Spinal cord injury can lead to an exaggeration of transmission through spinal pathways, resulting in muscle spasticity, chronic pain, and abnormal control of blood pressure and bladder function. These conditions are mediated, in part, by N-methyl-D-aspartate (NMDA) receptors on spinal neurons, but the effects of cord injury on the expression or function of these receptors is unknown. Therefore, antibodies to the NMDA-R1 receptor subunit and binding of [3H]MK-801 were used to assess NMDA receptors in the spinal cord. Receptor density in rats with intact spinal cords was compared to that in rats 1 and 2 weeks after spinal cord transection (SCT) at the mid-thoracic level. At 1 and 2 weeks after SCT, [3H]MK-801 binding was reduced in most laminae in cord segments caudal to the injury, whereas no decrease in amount of R1 subunit immunoreactivity was observed. No significant changes in [3H]MK-801 binding and NMDA-R1 immunoreactivity could be seen rostral to the transection. Since [3H]MK-801 binding requires an open ion channel, the discrepancy between [3H]MK-801 binding and immunocytochemistry may indicate a loss of functional receptors without a consistent change in their total number. Therefore, the exaggerated reflexes that are well established in rats 2 weeks after cord injury must be mediated by a mechanism that withstands attenuation of NMDA receptor function.

Long term effects of spinal cord transection in Zebrafish: swimming performances, and metabolic properties of the neuromuscular system

This study concerns functional recovery of zebrafish following spinal cord transection. Spinal cords were transected at the level of the 14th vertebra, just rostral to the dorsal fin. Recovery was tested at one month after transection when descending fibers start to regrow across the transection site and at three months after transection when fish perform kick and glide swimming. To estimate the rate of regrowth across the lesion site we analysed the tyrosine hydroxylase (TH) and dorsal 5-hydroxytryptamine (5-HT) systems in distal parts of lesioned cords. Both systems have cell bodies in the brainstem and in control fish TH- and dorsal 5-HT-containing fibers descend to all spinal segments. Swimming performance was studied by subjecting lesioned fish to endurance tests in a swimming tunnel with water flowing at a constant rate of 2 or 4.5 body lengths per second (BL/s). At 2 BL/s slow myotomal muscles are active whereas at 4.5 BL/s fast myotomal muscles are recruited. Control fish endured sustained swimming at both speeds for at least 3 hours. As a measure for the condition of the neuromuscular system in trunk and tail, we analysed aerobic metabolic capacities, assessed by NADH-tetrazolium reductase (NADH-TR) histochemistry of myotomal muscle fibers and spinal lateral neuropil. We found that TH- and dorsal 5-HT-immunoreactive fibers were absent in the entire distal part of lesioned cords at one month but at two months after transection they were present at approximately 6000 microns caudally to the site of the lesion. Thus the rate of outgrowth of these fibers is at least 200 microns per day. Sustained swimming at the slow speed (2 BL/s) could be endured for about 14.4 min at one month and for 23.5 min at two months after transection; there was no further improvement in the period that followed. In contrast, in the 10 weeks following transection, fast swimming (4.5 BL/s) could be endured for about 5 to 6 minutes. A significant improvement was gained in the period of 10 to 12 weeks after transection when fish could endure the high speed for almost 15 min. The aerobic capacity of muscle fibers in distal parts of the body was not strongly affected by the lesion. The only important change in aerobic capacity was observed in the neuropil of distal parts of the cords where, at three months after transection, NADH-TR activity was increased to approximately 150% of control values. On the basis of our findings, we assume that it is not the condition of the neuromuscular system, but rather a deficient co-ordination between proximal and distal body parts of lesioned fish that accounts for the relatively poor performances in endurance tests. Furthermore, differences in timing of improvements in swimming at 2 and 4.5 BL/s indicate that the spinal circuitries serving the slow parts of the neuromuscular system recover at an earlier stage than those serving the fast parts.

Changes in the synaptology of spinal motoneurons in zebrafish following spinal cord transection

Effects of spinal cord transection on the synaptology of zebrafish spinal motoneurons were studied. The transection was made at the level of the 14th vertebra and the synaptology of motoneuron somata and dendrites was analysed at the level of the 21st to the 23rd vertebrae at one month and three months after transection. Horseradish peroxidase, applied to the myotomal muscle, was used to label motoneuron somata and dendritic branches in central and in lateral areas of the neuropil (referred to as central and lateral dendritic profiles). Boutons impinging on motoneurons were classified according to the morphology of the vesicles. We discerned R-boutons with spherical vesicles, F-boutons with flat vesicles and DC-boutons with at least one dense core vesicle. The apposition lengths of R-, F- and DC-boutons and the circumference of labelled profiles were determined to assess the proportional covering of boutons on somata and dendrites. Ratio's of covering with R- and F-boutons (R/F ratio) for somata, central and lateral dendritic profiles were 1.1, 2.1, and 2.1 in control fish and 0.5, 0.5 and 0.9 in lesioned fish at one month after transection, respectively. The total covering of motoneurons in lesioned fish was decreased by 20% on somata and by 30% on lateral dendritic profiles, whereas central dendritic profiles did not change significantly. At three months after transection the R/F ratio's for somata, central and lateral dendritic profiles were 0.5, 0.7 and 0.6, respectively. The total covering on somata and central and lateral dendritic profiles was at control levels. The anatomical aspects of the changes in synaptology indicate that in control fish 50 to 60% of the R-boutons on the motoneuron surface originate from descending axons. In contrast, almost all F-boutons seem to be from local origin.

Dexamethasone up-regulates mRNA for Na+,K+-ATPase in some spinal cord neurones after cord transection

We have studied the effects of spinal cord transection and of dexamethasone (DEX) treatment on mRNA biosynthesis of the Na+, K(+)-ATPase, a key enzyme necessary for neurotransmission, membrane repolarization and nutrient uptake in the CNS. In situ hybridization analysis revealed a significant reduction in mRNA for the alpha 3 catalytic subunit of the enzyme in medium and large size ventral horn neurones (1000-2300 microns2) but not in small cells (1000 microns2) 24 h after spinal cord transection. DEX treatment significantly reversed the transection effect in medium and large size neurones. It is suggested that up-regulation of mRNA expression for Na+,K(+)-ATPase may constitute an important mechanism by which glucocorticoids help to re-establish neuronal function after spinal cord injury.

GAP 43-like immunoreactivity in normal adult rat sciatic nerve, spinal cord, and motoneurons: Axonal transport and effect of spinal cord transection

Using immunofluorescence and cytofluorimetric scanning techniques in the rat, the fast anterograde and retrograde axonal transport of growth-associated protein-43-like immunoreactivity in normal sciatic nerves, and after spinal cord transection in the lower thoracic region, were investigated. Spinal roots and motor endplates in the peroneal muscles were also studied. For comparison, anti-synaptophysin (p38) was used. In intact adult animals, the amounts of immunoreactive growth-associated protein-43 increased linearly, both proximally and distally to the crush site, between 1 and 24 h after crushing the sciatic nerve. The accumulations were present in thick as well as in thin axons. Distal accumulations in the sciatic nerve were about 40–60% of the proximal amounts, indicating a recycling of organelles with growth-associated protein-43-like immunoreactivity. During the week after spinal cord transection, no clear changes were observed; the anterograde transport of growth-associated protein-43-like immunoreactivity showed a tendency to decrease at day 1 and then a tendency to increase, reaching 120% of control at seven days (not significant). Transported p38-like immunoreactivity showed similar but smaller changes. In the lumbar spinal cord gray matter many nerve terminals with growth-associated protein-43-like immunoreactivity were seen in intact animals. After spinal transection, these terminals gradually decreased, suggesting that they belonged to descending pathways. However, p38-positive terminals were not obviously decreased. After crushing ventral and dorsal roots, accumulations pf growth-associated protein-43-like immunoreactivity were present in thick axons in the ventral roots and in thin to medium-sized axons in the dorsal roots. In peroneal muscles, growth-associated protein-43-like immunoreactivity was present in some (but not all) motor endplates in all groups. These results indicate that: (i) growth-associated protein-43 is normally present in nerve terminals of many descending projections of the spinal cord; (ii) growth-associated protein-43-like immunoreactivity is expressed and bidirectionally transported in neurons (motor as well as sensory) of normal sciatic nerves; (iii) growth-associated protein-43-like immunoreactivity is present in some adult motor endplates; and (iv) inhibited supraspinal input causes minor, if any, alterations—paralleled by p38—in axonal transport of growth-associated protein-43-like immunoreactivity.

Effects of spinal cord transection and MK-801 on CGRP immunostaining in the rat urinary bladder

Numerous studies have demonstrated that lesions in the CNS can alter the density of sensory nerve processes in peripheral organs. In the present study, rat spinal cords were transected at the second lumbar segmental level and the density of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the urinary bladder was examined. Additional rats had spinal cord transections followed by 12 days of treatment with the N-methyl- d-aspartate receptor antagonist, MK-801. In the bladders of control rats, CGRP-immunoreactive fibers were present as thick nerve trunks, perivascular plexi, and a fine meshwork of varicose nerve fibers. Twelve days following a spinal cord transection, the density of CGRP-immunoreactive nerve fibers was markedly reduced; occasional fibers appeared primarily as nonvaricose fine fibers. In bladders from rats receiving a spinal cord transection and MK-801 treatment, CGRP-immunoreactive fibers were abundantly distributed throughout the detrusor muscle; these fibers exhibited numerous varicosities as well as some enlarged terminal varicosities. These data demonstrate that (i) an upper motor neuron-type lesion markedly decreases the density of CGRP-immunoreactive peripheral afferent nerve processes and (ii) following a spinal cord transection, MK-801 appears to enhance the density of CGRP immunostaining in the bladder.

Evidence for descending tonic inhibition specifically affecting sympathetic pathways to the kidney in rats.

1. The present study investigated the possibility that pre- and postganglionic neurones innervating the kidney and spleen in rats are affected by descending inhibitory as well as descending excitatory influences. This hypothesis was tested by comparing the effects of cervical spinal cord transection to the effects of blockade of tonic activity of excitatory neurones in the rostral ventrolateral medulla (RVLM). 2. Electrical discharge of multifibre postganglionic renal and splenic and preganglionic greater splanchnic nerves and 13th thoracic (T13) white rami was recorded in artificially respired, urethane-anaesthetized rats. In one group of rats, descending supraspinal pathways were interrupted by cervical spinal cord transection. In another group, tonic activity of rostral ventrolateral medulla (RVLM) neurones was blocked by bilateral microinjections of the inhibitory amino acid glycine. The effects of spinal cord transection were compared to effects of this bilateral RVLM blockade and to effects of unilateral RVLM blockade described in a previous study. 3. Spinal cord transection caused decreases in preganglionic greater splanchnic and postganglionic splenic nerves which were of the same magnitude as those caused by bilateral blockade of the RVLM. 4. In contrast, discharge of renal nerves was decreased more by bilateral RVLM blockade than by cervical spinal cord transection. Similarly, even unilateral RVLM blockade caused greater decreases in discharge of T13 white rami than were caused by spinal cord transection. 5. These findings suggest that renal nerves and their preganglionic inputs (T13 white rami) are controlled in part by tonic sympathoinhibitory influences which can be unmasked by blockade of the RVLM. These sympathoinhibitory influences do not appear to affect the activity of splanchnic and splenic nerves.

Effects of spinal cord transection on sympathetic discharge in decerebrate-unanesthetized cats.

Previous experiments in our laboratory have shown that discharge of splenic, mesenteric, and splanchnic nerves is well maintained after spinal cord transection in chloralose-anesthetized cats (8, 9, 11). The primary purpose of this investigation was to determine if maintained sympathetic discharge could be observed after spinal transection in the absence of chloralose anesthesia. In cats anesthetized with alphaxalone-alphadolone, changes in splanchnic discharge, blood pressure, and heart rate caused by decerebration and removal of the forebrain were observed. This procedure decreased blood pressure, increased heart rate, and had no immediate effect on sympathetic discharge or its rhythm (assessed by power density spectral analysis). One hour after decerebration and termination of anesthesia, splanchnic discharge had increased by approximately 36%. Next, effects of spinal cord transection on discharge of splanchnic, mesenteric, and renal nerves were observed in the decerebrate-unanesthetized cats. Splanchnic discharge decreased by 50%, mesenteric nerve discharge was unchanged, and renal nerve discharge decreased by 97%. Therefore, splanchnic nerve discharge was not as well maintained in decerebrate-unanesthetized cats as it had been in chloralose-anesthetized animals, and the remaining splanchnic discharge appeared to affect mesenteric nerves preferentially. Finally, spectral analysis of the splanchnic discharge demonstrated that before cord transection, most of the signal was in the 0- to 6-Hz frequency range, whereas after transection the proportion of signal in this frequency range was significantly reduced and the proportion in higher frequencies (7-25 Hz) was significantly increased. This loss of low-frequency rhythmicity is consistent with findings in our previous studies in chloralose-anesthetized cats.

Effect of spinal cord transection in the newborn, weanling, and adult rat on the morphology of thoracic motoneurons

The midthoracic spinal cord was transected in neonatal ( N = 12), weanling ( N = 9), and adult ( N = 9) rats and sections were prepared at various postoperative survival periods (2 to 106 days p.o.) using a modified Golgi-Cox stain. The morphology of large lamina IX “motoneurons” was examined 0 to 5 mm rostral to the lesion border and compared with the morphology of similar cells from this region in developing and adult rats. Motoneurons examined in neonatal operates underwent the same temporal sequence of morphologic changes seen during normal development. Motoneurons in weanling operates underwent rapid morphologic changes which were most marked at the earliest period studied (2 days p.o.). These changes included a decrease in perikaryal diameter, dendritic loss, and the appearance of perikaryal and dendritic spines and varicose swellings. At the longest p.o. survival period analyzed (60 days p.o.), neurons had partially recovered but still retained somatic and dendritic spines and a reduced dendritic arbor. Motoneurons stained in adult operates showed no morphologic changes at 15 days p.o. but by 90 days p.o. somatic and dendritic spines were apparent, more similar to the morphology normally seen in the early postnatal period. We interpret these data to indicate that motoneurons surviving spinal transection are relatively unaffected by this lesion during the synaptogenic period and most severely affected when denervated near the end of this time. The more gradual appearance of regressive morphologic changes seen in adult motoneurons may indicate the continued partial denervation of these cells.

Blood-spinal cord barrier disruption proximal to a spinal cord transection in the rat: Time course and pathways associated with protein leakage

The effects of spinal cord transection on the blood-spinal cord barrier of the rat were examined at the ultrastructural level at sites 0.5 and 1.0 cm proximal to the injury. Using the vascular tracer horseradish peroxidase (HRP), the time course and pathways of barrier disruption were evaluated. At 0.5 cm, barrier disruption was noted from as early as 15 min and continued to 12 h after injury, whereas at 1.0 cm, evidence for vascular permeability was confined to between 15 min and 3 h. The presence of barrier breakdown to exogenous protein at a distance from the transection emphasizes that injury promotes a more generalized vascular response which likely contributes to subsequent edematous changes. The mechanism(s) involved in increased permeability appears to be primarily related to transendothelial vesicular transport of the tracer. There was no evidence for interendothelial leakage of the tracer across compromised tight junctions. In comparing these findings with those reported on sites distal to a transection, it is clear that there is an asymmetry in the vascular response to HRP. The pinocytotic index, an indicator of endothelial uptake of HRP, was significantly elevated (compared with control) distal to a transection from 3 h through 3 days after injury, attaining a maximum at 12 h. In contrast, the pinocytotic index proximal to a transection was significantly elevated compared to control values at only 1 h after injury. Furthermore, at 3 h after injury, when barrier disruption was most prominent, there was a smaller percentage of vessels exhibiting leakage to HRP proximal as opposed to distal to a transection.

Cryptorchidism in spina bifida and spinal cord transection: A clue to the mechanism of transinguinal descent of the testis

In spina bifida there is a high incidence of cryptorchidism, particularly where the lesion is at or above L2. This article describes the location of the testis in 32 spina bifida patients and the effect of spinal cord transection in neonatal rats: both studies suggest that the spinal cord influences testicular descent. It is already established that androgens, an intact genitofemoral nerve, and the gubernaculum are essential for the transinguinal phase of testicular descent to occur. Yet the mechanism by which testosterone exerts its effect on the gubernaculum remains obscure. To account for all the observed phenomena we postulate that a spinal cord nucleus may exist that is sensitive to androgens and mediates impulses through the genitofemoral nerve to the gubernaculum. Neuronal modulation of the gubernaculum may induce testicular descent.

The blood-spinal cord barrier after injury: pattern of vascular events proximal and distal to a transection in the rat

The effect of spinal cord transection on the blood-spinal cord barrier was examined at both the light and electron microscopic levels using the vascular tracer, horseradish peroxidase (HRP). At the light microscopic level, the pattern of hemorrhage and distribution of reaction product were examined and quantified at 0.5, 1.0, and 2.0 cm proximal and distal to the transection. The morphometric data supports the hypothesis that regions of the cord that are distal to a transection, exhibit a more pronounced vascular disruption than at comparable sites proximal to the injury. This asymmetry is not apparent until 1 day after injury and is characterized by an increase in the areas of hemorrhage and reaction product at 1.0 and 2.0 cm distal to the transection as compared to similar sites proximal. In previous ultrastructural studies we demonstrate that the primary mechanism for barrier breakdown distal to a transection appeared to be transendothelial vasular transport of the tracer. In the present study, we extended these observations to sites proximal to a transection and confirmed that a similar mechanism of barrier breakdown occurs. There was no evidence for interendothelial passage of tracer across compromised tight junctions. Further studies are under differences in the intensity of this response contribute to the asymmetry in barrier permeability demonstrated by light microscopy.

Somatovesical and vesicovesical excitatory reflexes in urethane-anaesthetized rats

The effect of spinal cord transection on excitatory somato- and vesicovesical micturition reflexes have been investigated in urethane-anaesthetized rats. In adult rats, 3 distinct types of excitatory reflexes to the bladder may be observed: a somatovesical reflex organized at spinal level and two vesicovesical organized at spinal level, respectively. In agreement with results of lesion experiments ( Neurosci. Lett. 8 (1978) 27–33), bladder voiding is abolished following spinal cord transection although both somato- and vesicovesical reflexes may be demonstrated in acute spinal rats. Occurrence of the spinal vesicovesical reflex during the collecting phase of the cystometrogram appears to be inhibited by a supraspinal inhibitory pathway.