Recruitment of alpha and gamma-motoneurons in rats, dogs and humans.

1. Single fibre action potentials were recorded with 2 pairs of wire electrodes from human and dog lower sacral nerve roots and the rat nervus suralis. From the widths of single peaks of alpha 1 (FF), alpha 2 (FR), alpha 3 (S) (extrafusal) and gamma 1 and gamma 21-motoneurons (intrafusal) conduction velocity frequency distribution histograms were constructed and the limits of the velocity ranges determined. Distribution changes of conduction velocities in each group of alpha and gamma-motoneurons were used for recruitment analysis in the occasional firing mode. 2. In the dog, the rat and the human, the slower conducting fibres were recruited before the faster conducting ones in each group of motoneurons. In the dog, the slowly conducting gamma 1 and alpha 2-motoneurons were recruited directly following bladder catheter pulling, and the slowly conducting alpha 3-motoneurons were recruited 1 sec later. In the rat, the slowly conducting alpha 1-motoneurons were recruited directly following pin-pricking of the hindlimb, the slowly conducting alpha 2-motoneurons 0.2 sec later, and the slowly conducting alpha 3-motoneurons 1 sec later. In humans, the slowly conducting gamma 1 and alpha 2-motoneurons were recruited 2 sec following bladder catheter pulling, the slowly conducting alpha 3-motoneurons 4 sec following pulling. 3. In the dog, with no additional stimulation slowly (and fast) conducting gamma 21 and alpha 3-motoneurons showed repeated activation 3 to 4 sec later. A subgroup of the alpha 1-motoneurons showed repeated activation every 2 sec. In the rat, without stimulation, a slower conducting subgroup of the alpha 1-motoneurons showed preferential activation of the low and high conduction velocities every 2 sec. In the human, with no additional stimulation, the slowly and fast conducting alpha 2 and alpha 3-motoneurons were recruited repeatedly every 2 sec.

Enhancement of nerve fibre regeneration by nucleotides after peripheral nerve crush damage. Electrophysiologic and morphometric investigations.

The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using both morphometric and electroneurophysiologic techniques. After a standardized localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UMP), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of nerve regeneration for comparison with age-matched crushed or nonoperated controls. Electroneurophysiologic studies of right sural nerves were performed as single fibre measurements. Morphometry was performed on semithin transverse sections of the right common peroneal nerve with a fully automatic interactive image analysis system. Forty days after crush injury the single fibre conduction velocity of all type II afferents in the UMP/CMP treated group was significantly accelerated. There was a trend (10% greater than or equal to p greater than or equal to 5%) to increase of mean efferent single nerve fibre function at this time. Morphometry of nerve fibres revealed a trend to enlargement of mean fibre area and mean fibre diameter related to increased myelin area and myelin thickness. After 60 days, there was a trend to increase of single fibre conduction velocity of all type II afferents in the UMP/CMP treated group. Automated morphometry revealed a significant increase for the following parameters: fibre area, fibre diameter, myelin area, myelin thickness and axon area.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration of nerve and muscle regeneration by administration of nucleotides--electroneurophysiological and morphometrical investigations.

The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using morphometric techniques. In addition morphometrical investigations of peroneal and soleal muscles were performed at different times. After a localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UM), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of common peroneal nerve regeneration for comparison with age-matched crushed or nonoperated controls. Forty days after daily UMP/CMP administration the single fibre conduction velocity of all type II afferents was significantly accelerated. There was a trend towards increased mean fibre area related to increased myelin area. Mean diameter of type II muscle fibres was increased. After 60 days, there was a trend to increase of single afferent fibre conduction velocity in the UMP/CMP group. In the same group automated morphometry revealed a significant increase of nerve fibre area, myelin area and axon area. At this time an increase was found of type I and/or type II muscle fibres in all animal groups. The present results suggest that both axons (neurons) and myelin sheaths (Schwann cells) of regenerating nerve fibres and regenerating muscle fibres are influenced by nucleotide administration.

[Acceleration of muscle regeneration by nucleotide administration. Experimental morphometric studies]. / Beschleunigung der Muskelregeneration durch Nucleotidapplikation. Experimentelle morphometrische Untersuchungen.

Morphometric studies of the peroneus longus muscle as well as of the soleus muscle were performed 20, 40 and 60 days after crush injury of sciatic nerve and continuous administration of nucleotides. 96 female Wistar rats were used in the experiments. Under ether anesthesia a crush injury was performed on the right sciatic nerve. 53 rats were injected daily with nucleotides (uridine monophosphate [UMP], cytidine monophosphate [CMP] or UMP plus CMP [UMP/CMP], respectively), and 43 control animals were given injections of saline. Morphometric studies of right peroneus longus and soleus muscles were performed with the aid of a semiautomatic technique to measure muscle fibre diameters. After 20 days there were no differences between mean muscle fibre diameters. 40 days after the beginning of the experiments semiautomated morphometry revealed an increase of type II fibre diameters in the UMP/CMP group. There were enlargements of type II fibres in the UMP and the CMP group after 60 days. At the same time larger diameters of type I fibres were found in the UMP/CMP group (trend) and in the UMP group. In conclusion the results presented here indicate, that the administration of nucleotides possibly represents a new opportunity for the treatment of traumatic nerve and muscle lesions.

[Systematic classification of the disorders of the peripheral nervous system]. / Systematik der Krankheiten des peripheren Nervensystems.

Classification of disorders in the peripheral nervous system has been a controversially disputed subject. A brief account, therefore, is given of basic definitions and main groups of mononeuropathies and polyneuropathies. The most common types of mononeuropathies as well as hereditary and acquired polyneuropathies are listed in four tables. Particular attention is given to toxic neuropathies.

[Pathomorphology of mucopolysaccharidoses]. / Pathomorphologie der Mucopolysaccharidosen.

Mucopolysaccharidoses are autosomal recessive or X-linked hereditary lysosomal storage diseases occurring to one in 10,000 to 16,000 births. The definitive diagnosis is based on the biochemical verification of the enzyme defect in cultured fibroblasts of amniotic fluid cells, in amniotic fluid, in chorionic biopsies and by determination of the urinary excretion of glycosaminoglycans. Morphological studies are of utmost importance both for genetic counselling and enlightenment of the pathogenesis. In recent years, numerous reports appeared dealing with morphological changes in different types of mucopolysaccharidoses. Based on own studies in pre- and postnatal cases, the present paper gives an update review on light and electron microscopic peculiarities of the different types and subtypes of mucopolysaccharidoses according to the classification of MCKUSICK and NEUFELD (1983). Lysosomal storage is found in practically all organs. However, there are quantitative and qualitative differences which are responsible for variations in clinical symptomatology. The purpose of this paper is to describe these differences with particular emphasis on changes in various tissues, on the pathogenetic mechanism of the storage as well as on pre- and postnatal morphological diagnostics.

[The nosological situation of hereditary motor and sensory neuropathies (HMSN, Charcot-Marie-Tooth disease, neural muscular atrophy)]. / Zur nosologischen Stellung der hereditären motorischen und sensiblen Neuropathien (HMSN, Charcot-Marie-Tooth-Krankheit, neurale Muskelatrophie).

Hereditary motor and sensory neuropathies (HMSN) comprise a heterogeneous group of disorders. Since phenotypic manifestations are similar in most families, classification is based on differences in the mode of inheritance, onset and progression of the disease, nerve conduction velocity and nerve biopsy findings. Autosomal dominant, autosomal recessive, X-dominant and X-recessive forms, substantial intrafamilial differences, intermediate forms and the combination of neuropathies with spinocerebellar degeneration within one and the same sibship have been described. On the basis of selected own cases it is demonstrated that there is a broad spectrum of functional and structural abnormalities depending on the progression of the disease and on the site of nerve studied (proximal or distal part). Both the neuronal and hypertrophic variants begin with axonal degeneration of the dying back type followed by segmental demyelination and variable degrees of hypertrophic Schwann cell proliferation. Constantly, posterior columns of the spinal cord reveal fiber loss. Since the molecular basis of the different forms remains to be clarified it seems to be of greater interest to underline common features than to separate seemingly different nosological entities. It is suggested that the latter are partly the result of a selection of cases with a variable severity. Evidently, the syndrome of myatrophic ataxia comprises apart from "pure" HMSN with unsignificant degenerations of posterior columns and "pure" Friedreich's ataxia with mild peripheral nerve fiber loss intermediate forms.

[Fully-automatic microscopic image analysis and measuring of single fiber conduction velocity in the sural nerve of short-term diabetic rats]. / Vollautomatische Mikroskopbildanalyse und Messung der Einzelfaserleitgeschwindigkeit am N. suralis kurzzeitdiabetischer Ratten.

Contrasting to the usual measurement of nerve conduction velocity, which only determines the conduction of the fastest fibers, single fiber measurement allows the registration of the conduction velocity of different fiber classes. The present experiment was performed to study whether electroneurophysiological and/or morphometrical parameters of group II fibers have changed after shortterm diabetes mellitus. Diabetes was induced in 28-d-old Lewis 1A-rats by administration of 60 mg/KG b.w. Streptozotocin. 60 d later, with the aid of an oscilloscope VKS 22-16 (VUKO Elektronische Geräte GmbH, Mühlheim) single fiber measurements were performed. Morphometry was carried out on semithin transverse sections of sural nerve with an automatic image analysis system A6471-AMBA/R (Robotron, Dresden). The mean plasma glucose level of diabetic animals was 27.1 +/- 2.7 mmol/l. The mean afferent conduction velocity was significantly reduced in diabetic animals. Furthermore, efferent fibers could be verified in sural nerve which showed also reduced conduction velocity in diabetic rats. Morphometry revealed significant reduction of thickness and area of myelin sheaths, whereas area of axons remained unchanged. Electroneurophysiological and morphometrical changes will be discussed with special emphasis to different fiber groups. It is suggested, that primary Schwann cell lesion is responsible for the observed findings.

[Automatic microscopic image analysis of semithin sections of peripheral nerves using the program Image-C/Nerve-Neuropathy]. / Automatische Mikroskopbildanalyse von Semidünnschnitten peripherer Nerven mit dem Programm Image-C/Nerv-Neuropathie.

Visiomanual morphometric analysis of peripheral nerve fibres has proved to be error-laden and inadequate. An automatic interactive programme was, therefore, developed for microscopic image analysis and feature extraction. Contours of myelin sheaths were properly identifiable, but an interactive programme component was found to be required to measure the remainder of two to 5% of fibres. Image analysis is shown to generate descriptive statistical features.

[The peripheral nerves of non-diabetic rats after streptozotocin administration using automatic microscopic image analysis]. / Untersuchungen an peripheren Nerven der nichtdiabetischen Ratte nach Streptozotocin-Applikation mit Hilfe der automatischen Mikroskopbildanalyse.

Electrophysiologic studies of posterior tibial nerves by averaging method and morphometric investigations of sural nerves by automatic image analysis were performed in 7 non-diabetic rats 42 d after the administration of 55 mg streptozotocin/kg b.w. and in 10 untreated controls. Morphometry of stained semithin sections was carried out with system A 6471-AMBA/R (Robotron, Dresden, G.D.R.). There was no decrease of motor nerve conduction velocity in streptozotocin injected animals. The investigated morphometric parameters showed no significant alterations in the streptozotocin group. The studies show that in streptozotocin diabetic rats electrophysiological and morphological alterations of the peripheral nerve are caused by hyperglycemia but not by direct neurotoxic effects of streptozotocin.

[Morphometric studies of peripheral nerves and spinal ganglion cells in streptozotocin diabetic rats]. / Morphometrische Untersuchungen an peripheren Nerven und Spinalganglienzellen bei streptozotocin-diabetischen Ratten.

Morphometric studies of sural nerves and dorsal root ganglia cells L5 were performed in 8 diabetic rats 35 or 44d after the administration of streptozotocin and in 8 controls. Morphometry of photographed semithin sections was realized after whole body glutaraldehyde perfusion with semiautomatic MOP AM 02 and MOP Videoplan. The peripheral nerve showed no decrease of the total nerve area, number of nerve fibres or of myelinated area. Parameters area of fibres decreased in diabetic animals caused by reduction of myelin sheath thickness. There were no changes of mean neuron volume and maximal cell diameter in the dorsal root ganglia. Whereas in experimental short-term diabetes the peripheral nerves demonstrate morphologic changes correlating to biochemical abnormalities, no such correlations can be observed in the perikarya. It is suggested, that primary SCHWANN cell lesion is responsible for the observed myelin thickness reduction.

[Morphology of diabetic neuropathy]. / Morphologie der diabetischen Neuropathie.

The morphological findings in peripheral nerves in diabetic subjects are reviewed. Diabetes is probably the most frequent cause of neuropathy. However it does not constitute a single nosological entity but is comprised of a variety of clinical and morphological changes. These are considered to be the consequences of metabolic derangements resulting from chronic hyperglycemia. Distal symmetrical neuropathies, which are most common, are characterized by axonal degeneration and segmental demyelination with loss of nerve fibres and fibrosis. Remyelination and axonal sprouting occur. Microvascular changes consist of thickening and hyalinization of the walls of the vessels. On electron microscopy these vessels appear thickened and show reduplication of the basal lamina that surrounds the endothelial cells and pericytes. The morphological bases of proximal symmetrical motor neuropathy, as well as of focal and multifocal neuropathies are briefly described. The synopsis of current knowledge can be helpful in diagnosis and differential diagnosis of disorders of the peripheral nervous system.

[Experimental diabetic neuropathy. Morphometric studies of spinal ganglia cells in short-term streptozotocin-induced diabetes]. / Die experimentelle diabetische Neuropathie. Morphometrische Untersuchungen an Spinalganglienzellen der Ratte bei streptozotocinbedingtem Kurzzeitdiabetes.

Ganglion cells of both the left and right dorsal root ganglia L5 were investigated morphometrically in 8 diabetic rats 35 or 44 d after the administration of streptozotocin, as well as in 8 controls. The quantitative study included the analysis of mean neuron volume, maximal cell diameter, cell number per volume, by cell size class and the analysis of histograms. There were no changes in cell size. Whereas in experimental short-term diabetes the peripheral nerves demonstrate morphologic changes correlating to the biochemical abnormalities (reduced amino-acid uptake, decreased activity of Na+, K+-ATPase) no such correlations can be observed in the perikarya.

[Experimental diabetic neuropathy. Morphometric studies on the rat N. suralis in short-term streptozotocin-induced diabetes]. / Die experimentelle diabetische Neuropathie. Morphometrische Untersuchungen am N. suralis der Ratte bei streptozotocinbedingtem Kurzzeitdiabetes.

Morphometric studies of sural nerves were performed in diabetic rats 35 or 44 d, respectively, after the administration of 60 mg/kg b.w. streptozotocin. Morphometry of photographed semithin sections was performed after whole-body glutaraldehyde perfusion both with the semiautomatic MOP Videoplan and the MOP AM 02 (Kontron, Munich, F.R.G.). The following parameters were registered: Area of nerves and fibers, perimeter of fibers, diameter of axons, thickness of myelin sheaths, form factor. No decrease of the total nerve area or of the myelinated area were found. Parameters area of fibers, thickness of myelin sheath and form factor decreased in diabetic animals. Axon diameter, ratio axon diameter-myelin sheath thickness and perimeter of fibers increased in the diabetic nerves. It is suggested that primary Schwann cell lesion is responsible for the observed myelin reduction.