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PubMed1976

Cytospectrometric studies on the lactate dehydrogenase isoenzymes in functionally different neuron-neuroglia units. II. Species and strain differences and effects of histotoxic hypoxia and audiogenic convulsions.

Cytospectrophotometric determination of H- and M-forms of LDH has shown that in white mice as compared with Wistar rats the activity ratio of H- to M-forms is lower in cerebral cortex neurons but higher in spinal cord motoneurons. No statistically significant species difference has been found in cerebellum PURKINJE cells as well as in the perineuronal glia of all the areas studied. Rats of KRUSHINSKY-MOLODKINA strain with hereditary high sensitivity to audiogenic convulsions differed from Wistar rats only with higher H- to M-form activity ratio in cerebellum PURKINJE cells and in their glial satellite cells. Histotoxic hypoxia in mice due to KCN injection gave rise in 15 min to activation of M-forms of LDH in spinal cord motoneurons and spinal ganglia neurons, of H-forms in cerebral and cerebellar cortex neurons and of both forms in the neuroglial cells adjacent to cerebellum PURKINJE neurons. Audiogenic convulsions in KRUSHINSKY-MOLODKINA rats induced an increase of H-form activity of LDH in the perineuronal glia of spinal cord anterior horns and of M-form activity in cerebellum PURKINJE cells while decrease of M-forms of cerebellum neuroglia. An importance of multiple forms of enzymes for the fine functional regulation of the cell biochemical pattern is discussed.

Animals↗
PubMed1976

[Cytophotometric determination of the relationship between the chief isoenzyme forms of lactate dehydrogenase in the neuron--neuroglia system in different fuctional states of the nervous system].

In white mice, unlike the Wistar rats, the ratio of activities of H- and M-forms of lactate dehydrogenase (LDH) is lower in the cerebral cortex neurons but higher in the spinal cord motoneurons within the limits of sensitivity and correctness of the cytospectro-photometric method. No statistically significant species differences in the activity ratios of H- to M-forms of LDH were found in the Purkinje cells of the cerebellum, as well as in the perineuronal glia of all the areas studied. Rats of the Krushinsky--Molodkina strain with a hereditary high sensitivity to audiogenic convulsions differed from the Wistar rats only with a higher H- to M-form activity ratio in the Purkinje cells and in their glial satellite cells. The ratio of H-forms to M-forms of LDH did not differ significantly in the majority of the neuron types studied as well as in the neurons as compared with their glial satellite cells. Histotoxic hypoxia in mice due to KCN injection gave rise to activation of M-forms of LDH in spinal cord motoneurons and spinal ganglia neurons, of H-forms in cerebral and cerebellar cortex neurons and of both forms in the neuroglial cells adjacent to the cerebellum Purkinje neurons. Audiogenic convulsions in the Krushinsky--Molodkina rats induced an increase of the H-form activity of LDH in perineuronal glia of spinal cord anterior horns, and of the M-form activity in the cerebellum Purkinje cells with a decrease in the M-forms of the cerebellum neuroglia. An importance of multiple forms of enzymes for the functional regulation of the cell biochemical pattern is discussed.

Animals↗
PubMed1983

Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs.

The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves. The local treatment was more effective with regard to SP depletion in target areas when using alcohol as solvent than when capsaicin was dissolved in paraffin oil, while the functional deficits were similar. The SP nerves in the esophagus were mainly of vagal afferent origin, while the heart atrium seemed to have a dual innervation by both vagal and non-vagal SP nerves.

Animals↗
PubMed1985

Effects of combined use of acyclovir and antibody in athymic nude mice inoculated intracutaneously with herpes simplex virus.

Antiviral effects of acyclovir (ACV) and antibody were studied in athymic nude mice inoculated intracutaneously in the midflank with herpes simplex virus type 1. Three hours after virus inoculation, treatment was initiated. In ACV-treated mice, the development of skin lesions was inhibited and the mean survival time was prolonged as compared with controls. Treatment with ACV markedly reduced the viral titers both at the inoculation site and in the neural tissues (dorsal root ganglia, spinal cord and brain). Transfer of antibody was also effective in controlling infection as described previously. The use of ACV plus antibody was more effective than the use of ACV alone and in 5 of 17 mice the disease was completely inhibited. Furthermore, in the mice that survived, latent infections in the ganglia were also prevented. These results indicate that treatment with ACV plus antibody is highly effective against herpes simplex virus infection in the immunocompromised host.

Acyclovir↗
PubMed1990

Spinal cord stimulation in 112 patients with epi-/intradural fibrosis following operation for lumbar disc herniation.

A total of 112 patients with epi-/intradural fibrosis following operation for lumbar disc herniation were treated by spinal cord stimulation. Lumbosacral spinal fibrosis is seen particularly often after extensive and repeated operations. Radicular pain responds better to stimulation than back pain. A favourable long-term effect on radicular pain has been observed in 67% of patients treated by epidural implantation, the corresponding average follow-up period being 4 1/2 years. 40% of these patients needed less analgesics after the operation, while 25% of them showed an improved fitness for work. Among about 5,000 patients who underwent surgical treatment for lumbar disc herniation, an indication for spinal cord stimulation was found in 1.5%. By comparison, the frequency of the "last resort" procedure of microsurgical cordotomy was 0.3%. We no longer use other ablative methods like extirpation of spinal ganglia.

Analgesia, Epidural↗
PubMed1996

Immunochemical study of galanin in the cat digestive tract and autonomic ganglia.

The presence of galanin was examined in the cat gut and related autonomic nervous structures using radioimmunoassay (RIA) and high performance liquid chromatography (HPLC). In the gut wall, the concentration of galanin-like immunoreactivity (GAL-Lt) was assayed separately in the muscular layers with the nervous plexuses and in the mucosa and ranged from 0.35 to 0.55 pmol/g wet tissue. In the autonomic nervous structures, GAL-L1 concentrations ranged from 0.22 (thoracic spinal ganglia) to 0.81 (inferior mesenteric ganglion) pmol/g wet tissue. The presence of galanin was checked by HPLC in the antrum, intestine, and colon. HPLC of extractable material revealed a major peak coeluting with the synthetic porcine peptide and minor earlier peaks representing likely different molecular forms of galanin. Our study strengthens the notion that galanin acts in nervous control of the cat gut functions.

Animals↗
PubMed1995

Peripheral projections of rat primary sensory neurons immunoreactive for neurotrophin 3.

Sensory neurons can be classified into subpopulations based on a variety of characteristics, including their morphology and physiological modalities. Whether any of these classifications correlates with neurotrophic sensitivities has not been determined. We have recently reported that a subpopulation of large diameter sensory neurons of the rat contain neurotrophin 3-like immunoreactivity (NT3-ir). In this study, we have further characterised NT3-ir sensory neurons by their size, segmental localization, and peripheral projections by combined techniques of retrograde tracing and immunohistochemistry. The size distribution showed that NT3-ir was localised to a subpopulation of large-diameter neurons ranging from 560 to 3,120 microns2. Greater numbers of NT3-ir neurons reside in trigeminal (43% of total), cervical (36%), and lumbar (39%) than in thoracic spinal ganglia (13-17%). In combination with Fluoro-Gold retrograde tracing, it was found that about 30% of sensory neurons projecting to the tibial muscle were NT3-ir, compared with 39% for tendon, 50% for whisker hair follicles, 17% for subdermis or epidermis, and only 1% for kidney or adrenal gland. These studies indicate that NT3-ir sensory neurons mainly project to skin and muscles but not viscera. Thus, the characterization of NT3-ir spinal sensory neurons suggests that large sensory neurons subserving proprioception and mechanoception require NT3 for the maintenance of normal function.

Animals↗
PubMed1991

Nerve growth factor differentially modulates the expression of its receptor within the CNS.

The effect of nerve growth factor on the expression of nerve growth factor receptor in the central nervous system of newborn and adult rats was studied by means of immunohistochemistry with the monoclonal antibody 192-IgG. Both during development and in adulthood, the intracerebroventricular administration of nerve growth factor elicited a pronounced increase of nerve growth factor receptor-like immunoreactivity in the cell bodies and neural processes of the basal forebrain cholinergic nuclei, as compared to cytochrome c-treated rats (controls). A pronounced nerve growth factor-induced increase of nerve growth factor receptor-like immunoreactivity was also observed in central regions innervated by trigeminal and spinal ganglia. A moderate to a marked increase of nerve growth factor receptor-like immunoreactivity was evident in some mesencephalic visual system-related structures and thalamic nuclei expressing nerve growth factor receptor. In contrast, NGF treatment did not induce appreciable modification of nerve growth factor receptor-like immunoreactivity in cerebellar, brainstem, and spinal motor structures of newborn rats. In adult nerve growth factor-treated rats, a decrease of nerve growth factor receptor-like immunoreactivity was detected in the cerebellum, whereas no re-expression of nerve growth factor receptor-like immunoreactivity occurred in the motor structures that had expressed it in the first postnatal week. Finally, nerve growth factor was also found to enhance, in both adult and newborn rats, nerve growth factor receptor-like immunoreactivity associated with ependymal and subependymal cellular elements of the lateral and third ventricles, as well as with the leptomeninges overlying the superior colliculus and supraoptic area. The present results indicate that endogenous nerve growth factor or nerve growth factor-like molecules may play a dynamic role in a variety of cell populations of both the developing and mature mammalian central nervous system. We thus propose the nerve growth factor ability to modulate its receptor in vivo as a novel criterion to define nerve growth factor or nerve growth factor-like molecules, sensitive neuronal, and non-neuronal cells. Whereas this criterion does not intrinsically possess absolute physiological validity, its pharmacological concomitants might be relevant in view of the proposed therapeutical use of this trophic factor.

Aging↗
PubMed1975

Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section.

Chemical properties of substance P in the spinal cord and dorsal roots of the cat were examined by gel chromatography and paper electrophoresis. The results suggest that the substance is identical with the undecapeptide, hypothalamic substance P, recently isolated from bovine hypothalamus. Distribution of substance P in the cat spinal cord (L5-S1) was investigated. Substance P was highly concentrated in the dorsal horn, where the highest level was found in the dorsal part. After the unilateral ligation and/or section of the dorsal roots, the level of substance P in the dorsal horn, particularly in its dorsal part, was markedly lowered. In the ligated and sectioned dorsal root, substance P was highly accumulated on the ganglion side, whereas its level was lowered on the central side of the ligature. These results suggest that hypothalamic substance P synthesized in the spinal ganglia is transported in the dorsal root toward their intraspinal axon terminals, where the substance is concentrated and serves as a neurotransmitter.

Animals↗
PubMed1984

The neuropathology of "typical" Friedreich's ataxia in Quebec.

We present the pathological data from the autopsies performed on 6 Friedreich's disease patients since the start of the Quebec Cooperative Study. All patients met the strict diagnostic criteria of the QCSFA. The anatomical lesions found in the peripheral and central nervous system were similar in all 6 cases and do not differ from those described in the literature. The clinical findings correlate closely with the histological lesions found in the peripheral nervous system and spinal cord. The evidence of segmental demyelination and remyelination in the spinal ganglia and posterior roots further supports the dying-back axonopathy hypothesis.

Adolescent↗
PubMed1987

Light and ultrastructural studies in sural biopsies of the pseudopolyneuropathic form of ALS.

The aim of this work was to study the neuropathological picture of the sural nerve in the pseudopolineuropathic form of A.L.S. Five patients were considered: in all cases the clinical and electromyographic follow-up excluded other diseases. EMG-studies were repeatedly performed: they showed the progressive evolution of the spinal anterior horn cell pathology from lower spinal to cervical levels. The sural nerve was processed according to the procedure used in our laboratory for light and ultrastructural examination. Quantitative analysis of myelinated fiber density was carried out on photographic enlargement and reported on histograms. The light and ultrastructural examination showed a severe loss of myelinated fibers; the decrease affected all types of fibers, but predominated in the largest ones. In the axons there was an increase of mitochondria, dilation of the small vesicles and increase in the number of neurofilaments. It is our opinion that all histopathologic data obtained in the sural nerve biopsy in this form of A.L.S. reveal a clear involvement of the sensory neurons of the spinal ganglia and the results can be useful for the study of precocius lesions in the A.L.S.

Amyotrophic Lateral Sclerosis↗
PubMed1976

[Changes in the innervational connections of the urinary bladder upon experimental stimulation of the hypothalamus].

The innervation of the urinary bladder was studied in 40 rabbits, 5 of which were control and in 35 animals the posterior and anterior nuclei of the hypothalamus were stimulated by electric current through bipolar electrodes. The efferent innervation connections in whose terminal plexuses there occurred absorption of catecholamines were shown histochemically and neurohistologically to be involved in the pathological process. Reactive and degenerative changes were found to take place in receptory nerve terminations, and first of all in free ones. Then the bodies of pseudounipolar neurons of spinal ganglia were changed. Changes were also found in the connections of sensory neurons with the cells of Goll's and Burdach's nuclei.

Animals↗
PubMed1986

Perhexiline-induced lipidosis in the dark Agouti (DA) rat. An animal model of genetically determined neurotoxicity.

Perhexiline maleate, an antianginal compound, may cause severe adverse effects such as weight loss, hepatic dysfunction and peripheral neuropathy in a small proportion of patients. Since present evidence suggests that poor debrisoquine hydroxylators are at risk, we designed an experimental study comparing its neurotoxic effects in dark Agouti (DA) rats, with poor hydroxylation of debrisoquine with that in Sprague Dawley (SD) rats, which are vigorous hydroxylators. Light and electron microscopic investigations revealed neurotoxic changes in DA rats after cumulative doses which did not cause any changes in SD rats. Although there was no evidence of hepatic disturbance, morphological examination disclosed a heavy lipid deposition in neurons of dorsal root and sympathetic ganglia in DA rats. This was correlated with increased plasma and tissue concentrations of the drug. The lipid accumulation was similar to that observed in man with perhexilene-induced neuropathy. Our results suggest that perhexilene neurotoxicity in the DA rat is related to a genetically determined impairment of hydroxylation. The DA rat may serve as an animal model for investigating the potential neurotoxicity of drugs which are metabolized by hydroxylation of the debrisoquine type.

Animals↗
PubMed1990

Neuroleptic-induced "painful legs and moving toes" syndrome: successful treatment with clonazepam and baclofen.

The syndrome of "painful legs and moving toes" is characterised by spontaneous causalgic pain in the lower extremities associated with peculiar involuntary movements of the toes and feet. It has been observed after a variety of lesions affecting the posterior nerve roots, the spinal ganglia and the peripheral nerves. The pathophysiology of the syndrome is unknown. I report a patient who developed the syndrome during treatment for schizophrenia with the antipsychotic agent molindone hydrochloride. The patient's response to the combination of clonazepam and baclofen suggests that the pathophysiology of the "painful legs and moving toes" may be linked to impairment of spinal serotonergic and GABA functions.

Baclofen↗
PubMed1984

Reduced substance P-like immunoreactivity in hereditary sensory neuropathy of pointer dogs.

Two unrelated Pointer dogs, each from a breeding of normal parents which produced three affected pups in a litter of nine, began to bite their paws at 3 and 5 months of age. Insensitivity to painful stimuli was marked in the distal parts of the limbs and receded proximally. The affected dogs were euthanatized at 5 and 20 months because of acral mutilation and infection. Changes affecting the primary sensory neurons included: small spinal ganglia with reduced numbers of cell bodies, degeneration of unmyelinated and myelinated fibers in dorsal roots and peripheral nerves, and reduced fiber density in the dorsolateral fasciculus (dlf). Since nociceptive loss was the salient deficit in a neuropathy affecting primary sensory neurons, immunohistochemical studies focused on substance P, the undecapeptide imputed to mediate nociception at the first synapse in the spinal cord and brain. The localization and density of substance P-like (SPL) immunoreactivity was studied in three control dogs and the two Pointers by the indirect antibody peroxidase-antiperoxidase method. The spinal intumescences of the control dogs contained dense SPL-immunoreactivity in fibers of the dlf and the superficial laminae of the dorsal horn (i.e., laminae I, II, and the dorsal part of III). Immunoreactive fascicles on the lateral aspect of the dorsal horn and in the reticular process sent contributions medially to a plexiform fiber arrangement in lamina V. Medially, SPL-immunoreactive fibers were more loosely arranged in the internal third of laminae VI and VII and in lamina X.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Chemical injury of the spinal cord of the rabbit after intracisternal injection of gentamicin.

A single intracisternal injection of 0.4 ml of 1.25 and 2.5 percent gentamicin sulfate with preservative to healthy adult rabbits caused acute respiratory paralysis and severe seizure activity initially and paralysis of the limbs subsequently. In the white matter of the upper cervical spinal cord, multiple, minute, disseminated, spongy lesions were observed. They consisted of lysis of axis cylinders, edematous dilatation of myelin sheaths, and loss of astroglia and interfascicular oligodendroglia. Axonal end-bulbs formed at the periphery of the lesions. Clinically and morphologically, 0.025 and 0.25 percent gentamicin sulfate solution did not produce myelopathy. The spinal lesions were distributed differently from those of other chemical myelopathies in that they developed in the deeper white matter with sparing of marginal myelinated fibers. Circumscribed high concentrations and gentamicin, and vulnerability of myelinated axis cylinders and interfascicular oligondendroglia to gentamicin may be the main factors causing these lesions. When gentamicin sulfate without preservative was injected, neutrophil leukocyte infiltration occurred actively in the spongy lesions. In the cervical spinal ganglia some nerve cells underwent cytoplasmic vacuolation. In control animals a single intracisternal injection of saline or preservative did not result in the production of these lesions.

Animals↗
PubMedDate not supplied

Morphological studies of sural nerve biopsies in the pseudopolyneuropathic form of amyotrophic lateral sclerosis.

The aim of this work was to study the neuropathological picture of the sural nerve in the pseudopolyneuropathic form of amyotrophic lateral sclerosis (ALS). Five patients were considered: in all cases the clinical and electromyographic follow-up excluded other diseases. EMG-studies were repeatedly performed: they showed the progressive evolution of the spinal anterior horn cell pathology from lower spinal to cervical levels. The sural nerve was removed and immediately fixed in phosphate-buffered 2.5% glutaraldehyde and processed according to the procedure used in our laboratory for light and ultrastructural microscopy. Quantitative analysis of myelinated fiber density was carried out on photographic enlargements of 1 micron semithin sections and recorded on histograms. The light and ultrastructural findings revealed a severe loss of myelinated fibers, the decrease affecting all types of fibers, but predominantly the largest ones. In the teased fibers, Wallerian-like degeneration was observed. In the axons there was an increase of mitochondria, dilatation of the small vesicles, and an increase in the number of neurofilaments. It can be assumed from the histopathologic data that the neuropathologic pattern in the pseudopolyneuropathic form of ALS shows an axonal degeneration. It is our opinion that the histopathologic data obtained in the sural nerve biopsy in this form of ALS reveals a clear involvement of the sensory neurons of the spinal ganglia, and the results can be useful for the study of precocious lesions in ALS.

Adult↗