Cord Of Cat Research Articles

Phosphinic acid derivatives as baclofen agonists and antagonists in the mammalian spinal cord: an in vivo study

The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre- and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35,348, 36,742, 46,381, 52,432, 54,626 and 55,845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABAA agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre- and postsynaptic inhibitory effects of 3-aminopropyl-methyl-phosphinic acid (CGP 35,024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35,024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABAB receptors. Spinal pre- and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55,845 and 46,381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.

WGA-HRP Studies on the Fiber Connections from the Spinal Cord to the Deiters' Nucleus

The labyrinthine-spinal reflexes are influenced by the inputs from the cervical and lumbal propriocepters. We studied the afferent route by the retrograde WGA-HRP method in cats. After the injection of WGA-HRP into either the dorsal or the ventral Deiters' nucleus, labeled neurons were investigated in the spinal cord, the cerebellum, the contralateral vestibular nucleus complex and the brain stem nucleus. In this paper, we report the results in the spinal cord of cats. i) When WGA-HRP was injected into the dorsal Deiters' nucleus, labeled neurons in the spinal cord were found mainly extending from the cervical to the lumbosacral area of the spinal cord. A number of labeled cells were located predominantly in the contralateral cervical segments, while a small number of labeled cells was found ipsilaterally in the lumbosacral segments. ii) In the case of the ventral Deiters' nucleus, labeled neurons were found extending from the cervical to the upper thoracic area of the spinal cord. Localization of labeled neurons in the spinal cord was limited mainly to Rexed's laminae VII and VIII. These results suggest that the afferent fibers from the spinal cord to the Deiters' nucleus are closely related to the labyrinthine-spinal reflex.

Afferent inhibition and facilitation of transmission through the spinocervical tract in the anaesthetized cat.

1. Extracellular microelectrode recordings were made from single spinocervical tract (SCT) neurones in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. 2. Pairs of air-jet stimuli, 60 ms in duration, were used to investigate in-field afferent inhibition in SCT cells. One jet was used to condition the responses to another jet located at a different position within the excitatory receptive field and occurring at times from 100 to 1800 ms later. Fifteen neurones were tested and significant in-field inhibition was observed in all of them. 3. The in-field afferent inhibition was organized spatially in the sense that inhibition was generally strongest when conditioning and testing stimuli were close together and became weaker as they were moved apart. There was also a weak effect due to the strength of the conditioning response; when conditioning produced a strong response, from near the most excitable part of the receptive field, there was often a weak reduction in the test response from distant sites. The inhibitory areas defined in these experiments were generally less than 100 mm in length in units with excitatory receptive fields much longer than this. 4. The in-field afferent inhibition had a time course that lasted from 300 to about 1000 ms. 5. Afferent inhibition was also evoked by applying either air-jet stimuli to hairy skin outside, but close to, the excitatory receptive field or by applying a vibratory stimulus from a piezoelectric transducer (200 Hz) to glabrous skin of the toe pads or the central foot pad. These conditioning stimuli had durations of 20 or 60 ms. For convenience we call this inhibition 'out-of-field' afferent inhibition. 6. Out-of-field afferent inhibition was evoked from both glabrous and hairy skin areas outside the excitatory receptive field. It was common in neurones with receptive fields on the toes and of twenty-eight such neurones tested it was observed in twenty-four. This inhibition had a short latency (usually about 10 ms or less but occasionally up to 30 ms) and lasted for about the duration of the test stimulus (30 or 80 ms when the test stimulus was 20 or 60 ms respectively). It was often followed by a further period of inhibition, with a latency of between 50 and 100 ms and lasting for 60 up to 130 ms. 7. In thirteen SCT neurones more complex effects were seen.(ABSTRACT TRUNCATED AT 400 WORDS)

Stereometric characteristics of ultrastructure of presynaptic terminals in the dorsal horn of the cat spinal cord

Ultrastructure of 240 axo-dendritic presynaptic terminals (PT) in the dorsal horn of the spinal cord of cat was investigated using the morphometrical statistic method. Parameters describing shape and average spatial radius of the three-dimensional PT (approximated by irregular ellipsoid) were estimated on the basis of the morphometry of random PT sections using ideas of the theory of probabilities. A lack of correlation between the synaptic operative zone localization and features of the terminals' shape was demonstrated. The distribution of the spatial PT radii was obtained. The obtained distribution elicited the relatively small variability of these parameters.

Intracerebroventricular administration of β-endorphin releases immunoreactive met-enkephalin from the spinal cord in cats, guinea pigs and mice

It has previously been reported that β-endorphin, given intraventricularly, releases methionine-enkephalin from the spinal cord in rats. The present studies sought to determine whether β-endorphin, given supraspinally, also released immunoreactive met-enkephalin from the spinal cord in cats, guinea pigs and mice. Intracerebroventricular injection of β-endorphin caused a dose-dependent increase of the release of immunoreactive met-enkephalin from the spinal cord in these animals. The results support the hypothesis that the pharmacological actions produced by β-endorphin are mediated by the release of met-enkephalin.

Effects of cervical spinal hemisection on dihydromorphine binding in brainstem and spinal cord in cat

Cats were sacrificed 1–3 weeks after cervical (C 1-C 2) hemisection and receptor binding experiments were carried out with 4.0 and 0.6 nM concentrations of [ 3H]dihydromorphine ([ 3H]DHM); these concentrations were shown by Scatchard analysis to represent the approximate K d values of high and low affinity dihydromorphine binding sites in brain homogenates. Unilateral cervical hemisection produced significant (P < 0.05), bilateral, reductions in the levels of [ 3H]DHM binding in the periaqueductal gray (PAG; 35–40%) and mesencephalic reticular formation (MRF; 47–51%), medial pons (40–56%) and medial medulla (30–37%). In paramedial pons and medulla, numerical reductions in [ 3H]DHM binding were observed (18 and 28%) which did not achieve statistical significance. In spinal cord, significant reductions were observed in the dorsal (45%) and ventral (29%) ipsilateral but not contralateral quadrants. We believe that these results in the brainstem and spinal cord reflect in part the loss of opiate binding on spinobulbar terminals and bulbospinal terminals, respectively, following orthograde degeneration. These observations support the hypothesis that the analgetic effects of opiates in the brainstem may in part be mediated by the direct inhibition of transmission through spinobulbar terminals.

Influence of the organophosphorus compound DFP on inhibitory motor systems and esterase activity in the spinal cord of cats.

In high spinal cats, the acute time-dependent changes of both the activity of spinal reflex pathways and the activity of three different esterases (acetylcholinesterase, carboxylesterase and neurotoxicant target enzyme) in the spinal cord were investigated after intravenous application of the organophosphorus compound di-isopropyl phosphofluoridate (DFP). There is no general depression of spinal reflexes by DFP. While the recurrent inhibition is completely abolished for a long time and the reflexes to a flexor (PBSt) are depressed but with a shorter recovery time, the reflexes to an extensor (GS) are distinctly less depressed or even facilitated. Reflex pathways from skin afferents to motoneurones did not react in a uniform way to DFP, e.g. inhibitory nociceptive pathways were less affected than excitatory ones. Esterase activities were heavily depressed and recovered with different time courses. The acute DFP action cannot be explained by a uniform intoxication of all spinal functions but probably emerges from a differential action on different interneuronal systems.

Response properties of the neurons in the cervical cord to stimulation of the inferior alveolar nerve in the cat

The purpose of this study was to investigate the neuronal mechanisms of the clinical symptoms of unusual muscle stiffness and/or pain in the neck and shoulder sometimes observed in patients suffering from chronic pulpal or periodontal diseases. Physiological properties of the neurons responding to the inferior alveolar nerve stimulation (inferior alveolar nerve driven-neurons: IANDNs) were studied by recording single unit activities in the upper cervical cord in cats anesthetized with alpha-chloralose. The results were as follows: (1) IANDNs were widely distributed from the dorsal horn to the ventral horn in the gray matter of the cervical cord (C2 and C3). (2) IANDNs were subdivided into two types of neurons based on the latencies of the spike responses: fast-type (F-type) (n = 60) and slow-type (S-type) (n = 101). (3) Two possible pathways from the inferior alveolar nerve to the cervical spinal cord participating in these spike responses were assumed: one was through the trigeminal spinal nucleus and the other through Probst's tract by way of the trigeminal mesencephalic nucleus. These results suggest that the impulses originating from dental inflammatory loci might drive IANDNs in C2 or C3 and that their activities may evoke contraction of the neck muscles, resulting in their stiffness and cervical back pain.

Blockade of spinal pathways decreases pre- and postganglionic discharge differentially.

Although discharge of many sympathetic nerves decreases substantially on transection of the spinal cord in cats, firing of splenic and mesenteric postganglionic nerves continues unabated (R. L. Meckler and L. C. Weaver, Brain Res. 338: 123-135, 1985; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155-172, 1988). Therefore, ongoing sympathetic outflow directed to the splanchnic circulation was proposed to be less dependent on supraspinal excitatory drive than that directed to other vascular beds. Blockade or transection of cervical spinal pathways in chloralose-anesthetized cats significantly decreased firing of gastric, hepatic, adrenal, and lumbar chain sympathetic nerves. Discharge of gastric and hepatic nerves decreased as much as that of adrenal and lumbar chain nerves; therefore, sustained discharge in the absence of bulbospinal excitation is not a characteristic of all sympathetic nerves innervating the splanchnic circulation. In contrast, discharge of the preganglionic greater splanchnic nerves was not decreased after spinal transection, although it changed from a rhythmic to an asynchronous pattern. This provocative finding suggests that rhythmicity of preganglionic discharge may be important for effective synaptic transmission to some postganglionic neurons, since postganglionic gastric, hepatic, and adrenal nerve firing decreased in the presence of sustained but asynchronous preganglionic input.

Ultrastructure of the central gray region (lamina X) in cat spinal cord

The central gray region (lamina X) of the lumbar spinal cord in cat was examined by electron microscopy. This region consisted of three morphological zones. Medially, the first zone was comprised of ependyma which surrounded the central canal. The ependyma in the cat spinal cord was similar to most vertebrate spinal ependyma. Secondly, a subependymal zone consisted of glial processes arranged parallel to the long axis of the spinal cord. This glial zone was widest lateral to the central canal and extended approximately 75 μm. The lateral edge of the glial zone intermingled with a neuropil zone, the third zone. The components of the neuropil zone consisted of dendrites, myelinated and unmyelinated axons, synaptic terminals, astrocytes and neurons. The dendrites and neurons generally were oriented parallel with the long axis of the spinal cord. Three synaptic terminal types were categorized according to vesicular morphology, i.e. small round vesicles, flattened vesicles and dense core vesicles. The central gray region has been implicated in nociception and has been shown to receive both primary afferent and supraspinal input. The results from this study are consistent with the central gray region being an area of multiple synaptic inputs which may form the morphological basis of nociceptive processing that ascends to brainstem nuclei.

Effect of naloxone in experimental acute spinal cord injury.

Naloxone, an opiate antagonist, has been reported to improve spinal cord blood flow and restore the neurological function of spinal cord in experimental animals. The present study investigated the short term effect of naloxone infusions in acute preparations. An impact of a 20-g weight dropped from 6 cm high was used to traumatize the thoracolumbar spinal cord in cats. Treatment was started immediately after trauma. The naloxone-treated cats received intrathecal (2 mg in 0.5 ml) as well as systemic (2-mg/kg bolus, 2 mg/kg/hour for 4 hours) doses of naloxone. In the control group, equal volumes of saline were administered. The physiological integrity of the spinal cord as measured by averaged spinal evoked potentials (SEPs) ceased immediately after trauma in both groups. No recovery of the SEP in response to sciatic nerve stimulation occurred in either group during the 4 hours of treatment and monitoring in this study.

Characterization of forms of immunoreactive somatostatin in sensory neuron and normal and deafferented spinal cord

In order to determine the contribution made by primary sensory afferents and supraspinal projections to the immunoreactive somatostatin (IRS) content of the spinal cord, measurements were made of the concentration of IRS in the dorsal and ventral halves of the cord in cats subjected to unilateral lumbosacral dorsal rhizotomy (L1-S3) alone or combined with spinal cord transection. The molecular forms of IRS (characterized by gel chromatography) in L7 lumbar spinal cord, L6-S1 dorsal roots, ventral roots and dorsal root ganglia, and sciatic nerve were also determined. S14 was the predominant form in all tissues examined, but two additional molecular forms corresponding to S28 and S11.5 kdalton were present in dorsal root ganglia and spinal cord; S28 but not S11.5 kdalton was detected in both dorsal roots and sciatic nerves. These results indicate that S14 and S28 and S28 are transported along the central and peripheral processes of dorsal root ganglia, but that spinal cord S11.5 kdalton originates in the central nervous system. IRS in the dorsal horn was reduced by ca. 40% following dorsal root section. Neither disruption of descending pathways by spinal transection nor surgical isolation of the lumbar segements lowered cord somatostatin content below that produced by dorsal root section, indicating that most of the somatostatin within the cord arises from the dorsal root and from neurons in local spinal segments. Although the total content of IRS in the dorsal horn was reduced by ca. 40% following dorsal rhizotomy, the pattern of molecular forms was not changed accordingly. Since S14 and S28 but not S11.5 kdalton are transported via the dorsal root, the dorsal root section would be predicted to produce a relatively greater decrease in S14 and S28 than in S11.5 kdalton. Therefore, failure to find a selective loss of S14 and S28 suggests that dorsal rhizotomy affects dorsal horn IRS content not only by removing afferent input but possibly also by modifyinh the processing of IRS by the remaining somatostatinergic neurons.

Recovery of locomotor function after hemisection of the spinal cord in cats

Cats were subjected to high lumbar hemisection of the spinal cord, on the right side. The initial paralysis of the right hindlimb became rapidly attenuated, and they walked again in one week or less after surgery. Minor residual deficits in gait remained, that may be permanent. Electrical stimulation of the bulbar reticulospinal formation showed residual crossed connections reaching the right lumbosacral cord via the left hemicord. Recovery from Brown-Séquard's syndrome may be primarily due to the survival of low crossing descending projections to the spinal cord.

The effects of drugs on the dorsal SBS reflex after ischemia of the spinal cord in cats

The effects of drugs on the dorsal SBS reflex after ischemia of the spinal cord in cats

A neurophysiological analysis of the effect of kainic acid on nerve fibres and terminals in the cat spinal cord.

Kainic acid was administered micro-electrophoretically in relatively small amounts (approx. 0.15 nmol) near gastrocnemius motoneurones in the spinal cord of cats anaesthetized with sodium pentobarbitone. After initial excitation, extracellularly recorded orthodromic and antidromic field potentials were reduced. Such neurophysiological evidence for motoneuronal damage or death persisted for 5 h, the longest period of observation. At the site of administration, the terminations of gastrocnemius group Ia afferent fibres were electrically inexcitable for approximately 1 h. Subsequently, the number and excitability of these terminations appeared to be normal, as were the depolarizing actions at bicuculline-sensitive receptors of micro-electrophoretic piperidine-4-sulphonic acid and of gamma-aminobutyric acid (GABA) released at axoaxonic synapses on these terminations. Central myelinated and non-myelinated fibres and terminals of muscle group Ia afferent fibres, and the synaptic release of GABA on these terminals at axo-axonic synapses formed by certain spinal interneurones, thus appear to be relatively insensitive to kainic acid administered in amounts which damage or destroy motoneurones.

Concussive head injury producing suppression of sensory transmission within the lumbar spinal cord in cats.

This study examines the effects of concussive levels of a fluid-percussion head injury on sensory transmission within the lumbar spinal cord of the cat. Primary afferent depolarization (PAD) was suppressed for 2 to 5 minutes following injury, as assessed by dorsal root potentials and augmentation of antidromic dorsal root potentials, both evoked by stimulation of adjacent dorsal roots. Polysynaptic reflex discharges in ventral root potentials evoked by dorsal root stimulation were also profoundly suppressed during this same period, even when spontaneous and monosynaptic reflex discharges were facilitated. Changes in PAD produced by injury were abolished by spinal cord transection, but were not affected by midpontine transection. These findings suggest that concussive head injury can produce suppression of segmental sensory transmission by neurally mediated processes involving the bulbar brain stem. Recordings of dorsal root resting potentials, antidromic dorsal root potentials, and reductions of antidromic dorsal root potentials induced by tetanic root stimulation indicated that depressed segmental sensory function produced by injury was due to suppression of postsynaptic interneuronal transmission rather than to excitability changes in primary afferent fibers. Somatosensory cortical potentials evoked by dorsal root stimulation were profoundly depressed at the same time as segmental sensory transmission was suppressed, suggesting that suppressed segmental sensory transmission may also contribute to suppression of ascending sensory transmission. It is hypothesized that transmission failure of interneuronal systems in the initial period following insult may be a general response occurring in wide areas of the central nervous system, and not restricted to areas to which mechanical stress is directly applied. This response pattern may result from indiscriminate activation of interconnected excitatory and inhibitory elements of interneuronal systems.

Synaptic responses of propriospinal neurons to stimulation of the stepping strip of the dorsolateral funiculus in cats

Synpatic responses were recorded extracellularly from single neurons at levels T12–T13 in response to microstimulation of the stepping strip of the dorsolateral funiculus in the thoracic and cervical portions of the spinal cord in cats decerebrated at the precollicular level [4]. The latent periods of these responses increased when the distance between the stepping point and recording point exceeded 20 mm, and when two stimuli had to be applied in order to evoke responses. Axons of neurons respondingtrans-synaptically to stimulation of the stepping strip were located on the boundary between the lateral and ventral funiculi close to the gray matter. Antidromic responses of neurons sending their axons in the caudal direction were found on average in 37% of cases, provided that the distance between the recording and stimulation points did not exceed 40 mm. Half of the neurons which generated synaptic responses to stimulation of spinal stepping points could be excited also by a series of three to six stimuli, applied to the mesencephalic locomotor point [15]. It is suggested that the neurons discovered may participate in the spread of activity toward the generator of stepping movements of the hind limb.

O2C0936) - Converting effects of drugs on the dorsal SBS reflex after ischemia of the spinal cord in cats.

O2C0936) - Converting effects of drugs on the dorsal SBS reflex after ischemia of the spinal cord in cats.

Cardiovascular reflexes arising from the gallbladder and pancreas in spinal and in decerebrate cats

Cardiovascular responses to chemical stimulation of thin-fiber afferents from the gallbladder and pancreas were determined before and after C 1 transection of the spinal cord in cats. Additional cats were studied before and after decerebration. Stimulation of gallbladder and pancreatic afferents caused significant increases in arterial pressure and heart rate in all groups; however, smaller responses often occurred in spinal cats. These results demonstrate that spinal circuitry alone can generate cardiovascular responses to visceral stimulation and that supraspinal, though not necessarily suprapontine areas, are involved in producing the full response.

Carbon Dioxide Laser Destruction of Human Cervical Tissue I: Transmission Electron Microscopy Studies

INTRODUCTION The carbon dioxide laser destroys tissue by delivering intense energy to produce boiling of intra- and extra-cellular fluid. The vaporization of tissue leaves a crater, lined by debris and carbon particles. Beneath this crater is a zone of necrotic tissue, damaged by the conduction of energy (1,2). The details and extent of this zone have been demonstrated using transmission electron microscopy (TEM) around laser burns in the brain and spinal cord of cats (3,4), the tongue of dogs (5) and human skin (6). The carbon dioxide laser has recently been introduced to gynecological practice to treat premalignant lesions of the cervix (7-11). These lesions, now termed cervical intraepithelial neoplasia (CIN) (12,13), involve not only surface squamous epithelium but also the epithelium that invaginates the underlying stroma as crypts or clefts (14). From the data of Przybora and Plutowa (15), Anderson and Hartley (16,17) and Abdul-Karim et al. (18) the depth of this crypt involvement rarely extends bey...