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Biomedical subjects

H Lassmann

Publications and source records attributed to H Lassmann.

At least 253 records · Page 14Linked to original sources
PubMed1983

Etiology and pathogenesis of monophasic and relapsing inflammatory demyelination - human and experimental.

The close similarity of the CNS lesions in cr-EAE and MS renders this model especially valuable for the study of pathogenetic factors, leading to the formation of inflammatory demyelinated plaques. Recent evidence indicates, that various immune reactions, directed against different CNS antigens cooperate in the formation of the plaques. Furthermore it is discussed, that a combination of virus infection and autoimmunity may result in similarity structured lesions. It is thus propose that multiple different etiologic factors (autoimmune as well as exogenous events) may lead to the clinical pathohistological syndrome of multiple sclerosis.

Animals↗
PubMed1983

Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis.

Comparison of the pathohistology of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) and multiple sclerosis (MS) reveals a close similarity. Thus, CR-EAE appears to be a valuable model for the study of pathogenetic factors leading to the formation of MS lesions, although the induction of the disease may be different (active sensitization with CNS antigens and adjuvant in CR-EAE versus unknown etiology in MS). CR-EAE furthermore mimicks the pathohistological patterns of other related human inflammatory demyelinating diseases (i.e., acute perivenous leukoencephalomyelitis and acute hemorrhagic leukoencephalomyelitis). The expression of an acute, predominantly inflammatory versus chronic inflammatory demyelinating disease in this model depends upon the time interval between sensitization and sampling of the animals. Recent evidence is discussed that a cooperation between cellular and humoral immune mechanisms, directed against multiple CNS antigens, is responsible for the formation of large demyelinated plaques in EAE and MS.

Animals↗
PubMed1983

In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis. Antibody nature of the demyelinating factor and the role of complement.

Sera from guinea pigs and rats with chronic experimental allergic encephalomyelitis were injected into the cerebrospinal fluid (CSF) of normal recipient rats. Guinea pig sera induced demyelination in the central and (or) peripheral nervous system, whereas injection of rat sera resulted in demyelination in the peripheral nervous system only. Control sera did not induce demyelination. Demyelinating activity in guinea pig sera was confined to the IgG-fraction; in rat sera the IgG- as well as the IgM-fraction were able to induce demyelination. The demyelinating activity was abolished when the sera were absorbed with with sensitising antigen (guinea pig spinal cord tissue) or when immunoglobulins were removed from the sera. When chronic EAE sera from rats were injected into the CSF of rats, complement was not required for the induction of demyeLination. The presence of complement, however, augmented the demyelinating activity. Decomplemented chronic EAE sera from guinea pigs failed to induce demyelination after injection into the CSF of rats. Injection of control and non-demyelinating or demyelinating EAE sera into the subarachnoid space of normal recipient rats induced a weak inflammatory response with increased numbers of large mononuclear cells in the meninges. It is discussed that in vivo a complex interaction of antibodies, complement and effector cells is responsible for induction of demyelination.

Animals↗
PubMed1983

Kainic acid induced seizures: neurochemical and histopathological changes.

Behavioural, histopathological and neurochemical changes induced by systemic injection of kainic acid (10 mg/kg, s.c.) were investigated in rats. The most pronounced behavioural changes were strong immobility ("catatonia"), increased incidence of "wet dog shakes", and long-lasting generalized tonic-clonic convulsions. The behavioural symptoms were fast in their onset and lasted for several hours. Two distinct phases of histopathological and neurochemical changes were observed. (1) Early partially reversible changes were seen up to 3 h after kainic acid injection. They consisted of shrinkage and pyknosis of neuronal perikarya together with swelling of dendrites and axon terminals. These changes were accompanied by generalized signs of edema throughout the whole brain. Neurochemically, there was a marked decrease in noradrenaline levels (up to 70%) and an increase in levels of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid (up to 200%) in all analysed brain regions, suggesting a strongly increased firing rate of aminergic neurones during the period of generalized seizures. These histological and neurochemical changes were found in all the brain regions examined; they were greatly reduced or only sporadically seen after 1-3 days, when the animals had recovered from the seizures. (2) Late irreversible changes developed 24 h and later following kainic acid injection. They consisted of incomplete tissue necrosis with loss of nerve cells and oligodendrocytes, demyelination, astroglial scar formation, small perivenous hemorrhages and extensive vascular sprouting. The changes were restricted to the pyriform cortex, amygdala, hippocampus (most pronounced in the CA1 sector), gyrus olfactorius lateralis, bulbus olfactorius and tuberculum olfactorium. Neurochemically, a selective decrease was seen in choline acetyltransferase activity (40%) of the amygdala/pyriform cortex area, and of glutamate decarboxylase activity in the dorsal hippocampus (45%) and amygdala/pyriform cortex (55%). No such changes were found in the frontal cortex and the striatum/pallidum. Since at these later time periods the widespread early changes in monoamine metabolism were mostly normalized, loss of acetylcholine and gamma-aminobutyric acid neurons in the affected brain regions represented a selective neurochemical change typical for this stage of kainic acid action. The observed neurochemical and histopathological changes may be directly related to the excitotoxic and convulsive properties of kainic acid. However, brain edema resulting in herniation damage of the basal portions of the brain in addition to disturbances of microcirculation and +

Amygdala↗
PubMed1983

Increased blood-brain barrier permeability in scrapie-infected mice.

The present investigation was designed to study the ultrastructural integrity of the blood-brain barrier (BBB) in the cerebral microvasculature of scrapie-infected mice showing clinical illness. Cerebral microvessels from either IM, VM, or C57BL/6J mice, terminally affected with various strains of scrapie agent showed a focal leakage of horseradish peroxidase (HRP) in all agent-strain and mouse-strain combinations. This leakage was most pronounced in and near the primary site of agent inoculation, but was also observed in microvessels scattered throughout the brain. Cytochemical studies also revealed a redistribution of plasmalemma-bound alkaline phosphatase in the endothelial cells. In control mice, the enzymatic activity was mainly concentrated in the luminal plasmalemma, while in the scrapie-infected mice the activity also appeared in the abluminal side in the majority of microvessels. Our observations are evidence that the BBB of the mouse is altered in some way by the scrapie agent. Such an alteration may have important implications for human disease, since the scrapie agent is related to the group of "slow" viral infections, including kuru and Creutzfeldt-Jakob disease. Scrapie may also serve as an important model for the study of senile dementia of the Alzheimer type (SDAT).

Animals↗
PubMed1982

Antibodies-restricted heterogeneity in serum and cerebrospinal fluid of chronic relapsing experimental allergic encephalomyelitis.

An animal model which might help to study multiple sclerosis has long been sought. With chronic relapsing experimental allergic encephalitis (EAE), the search seems to have brought hope and evidence of comparable pathology whether concerned with clinical or neuropathological results, but no study of the cerebrospinal fluid (CSF) electrophoretic pattern has been made so far. A new sensitive method enables to study the CSF proteins: unconcentrated CSF proteins after agar gel electrophoresis are stained with silver reagents. The silver technique allows to follow the evolution of the inflammatory reaction in chronic relapsing EAE as well as in the acute form of EAE. This technique provides an additional approach to the study of EAE and an argument in favor of chronic relapsing EAE in guinea pigs as a model for multiple sclerosis.

Animals↗
PubMed1982

Nasal glioma.

Light and electron microscopic studies in a case of nasal glioma revealed a tumor composed nearly entirely of astrocytes. No ganglion cells or neurons were present and the mass was not surrounded by a capsule reminiscent for meningeal tissue. The vasculature resembled dermal patterns rather than typical central nervous system. No bone defect or connection to endocerebral tissue could be detected in the present case. Nasal glioma represents an ectopic focus of astrocytes, comparable to a hamartoma, rather than a true tumor or a herniation of brain tissue.

Astrocytes↗
PubMed1981

Inflammatory demyelinating polyradiculitis in a patient with multiple sclerosis.

A case of multiple sclerosis (MS) occurred in which there were recent demyelinated plaques in the CNS, and inflammatory demyelination and remyelination in the peripheral (Schwann cell) portions of the spinal roots. The lesions in the peripheral nervous system (PNS) were characterized by inflammation, primary segmental demyelination, myelin stripping, the occurrence of lipid debris-containing macrophages in the endoneurium, and remyelination. To our knowledge, this is the first description of simultaneous acute inflammatory demyelination in the CNS and PNS in MS.

Acute Disease↗
PubMed1981

Fractionation of spinal cord tissue affects its activity to induce chronic relapsing experimental encephalomyelitis.

Chronic relapsing experimental allergic encephalomyelitis (EAE), an animal disease closely resembling multiple sclerosis, was induced in young guinea pigs by sensitization with guinea pig spinal cord tissue together with complete Freund's adjuvant and a high amount of mycobacterium tuberculosis. Sensitization of animals with myelin basic protein leads to an acute form of EAE, but not to a chronic demyelinating disease. The present study was designed to trace the factors of spinal cord tissue responsible for chronic disease and demyelination by using fractionated spinal cord tissue for sensitization. The following preparations were tested for encephalitogenic activity: a) total guinea pig spinal cord homogenized in chloroform/methanol (C/M), b) C/M residue (protein fraction), c) C/M extract (lipid fraction) and d) bovine brain gangliosides. C/M treated spinal cord preparations were less encephalitogenic as compared to untreated spinal cord. The protein fraction showed very little encephalitogenic activity, the histological changes were limited to perivascular inflammation without demyelination. A crude lipid fraction induced some chronic inflammation. Neither the purified lipid fraction nor gangliosides produced any EAE symptoms. The conclusion can be made that protein is necessary for the induction of chronic relapsing EAE, whereas lipid or a protein-lipid complex seems to be responsible for the demyelinating component of this disease.

Animals↗
PubMed1981

Isolated leptomeninges of the spinal cord: an ideal tool to study inflammatory reaction in EAE.

Isolated and stretched leptomeninges have several advantages for the study of basic mechanisms in inflammation of the CNS. They offer a three dimensional view of the vascular tree which has basically the functional characteristics of cerebral vessels (the tight barrier, excluding macromolecules to enter the CNS compartment). The limited, small thickness of the specimen facilitates the performance of histochemical and immunohistochemical methods.

Animals↗
PubMed1981

In vivo effect of sera from animals with chronic relapsing experimental allergic encephalomyelitis on central and peripheral myelin.

Sera from guinea pigs with acute or chronic relapsing experimental allergic encephalomyelitis (EAE) were injected into lumbosacral subarachnoid space of normal recipient rats. Seventeen of 37 sera induced demyelination in the CNS, and 27 of 37 sera caused demyelinated peripheral nerve fibers in the roots. The highest incidence of demyelinating activity of EAE sera was noted in those from donor animals sampled during the early chronic stage of the disease [40--100 days post sensitization (dps)]. Only few sera from animals sampled during the acute and subacute stage (10--40 dps) were able to induce demyelination. Sera from animals sampled between 100 and 200 dps showed a lower incidence of demyelinating activity as compared to those from the early chronic phase of the disease. There was no clear-cut correlation between the serum-demyelinating activity and the severity of the demyelinating disease in the donor animals. The patterns of demyelination in the central as well as peripheral nervous system of recipient animals were characterized by vesicular disruption of myelin or myelin stripping. Myelin degradation was performed mainly be macrophages. In the CNS some astrocytes also contained debris. Astrocytes increased in size, and mitosis of astrocytes was observed. Oligodendrocytes appeared to be unaffected. No demyelination was found when the sera from animals sensitized with CFA alone or with guinea pig liver tissue were injected into the subarachnoid space of normal recipient rats. Two possible mechanisms of demyelination are discussed: Antibody-mediated complement-dependent and antibody-dependent cell-mediated demyelination.

Animals↗
PubMed1981

Ultracytochemical studies of the blood-meningeal barrier (BMB) in rat spinal cord.

Alkaline phosphatase(AP),5'-nucleotidase(5'N) and nucleoside diphosphatase (NDPase) activities were studied by cytochemical methods applied to light and electron microscopy in the microvasculature of spinal cord leptomeningeal strips of normal and protamine sulfate (PS) treated rats. The increased permeability to intravenously injected horseradish peroxidase was observed in some segments of microvessels of PS treated rats. Enhanced formation of plasmalemmal pits and deep invaginations, formation of numerous pinocytic vesicles and the appearance of channel-like structures in the cytoplasm of endothelial cells were the most striking ultrastructural evidence of increased permeability of the affected microvessels. All of these structures also showed activity of AP, and to lesser extent, of NDPase; 5'N activity was mainly associated with the delimiting membranes of pinocytic vesicles. Our data present evidence that a shift of enzymatic activity from luminal to abluminal surface of affected endothelial cells results from membrane flow accompanying increased transport activity via formation of pinocytic vesicles and channel-like structures.

Alkaline Phosphatase↗
PubMed1981

Histogenesis of demyelinating lesions in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis.

Spinal cord lesions in Hartley guinea pigs with chronic relapsing experimental allergic encephalomyelitis (EAE) were studied by light, transmission and scanning electron microscopy at different stages of the formation of demyelinated plaques. In addition the inflammatory response in the meninges was studied in isolated pia mater preparations separated from the spinal cord surface. In initial chronic lesions in the spinal cord, inflammation was restricted to penetrating parenchymal veins of the spinal cord and meninges. With the formation of large demyelinated plaques in the spinal cord, massive fibrosis of the meninges with infiltration by inflammatory cells was noted in an area covering the surface of the lesion. In plaques which reach the spinal cord surface, inflammatory cells could be seen passing between the pia and the spinal cord substance. In chronic remyelinated lesions, adhesions between meningeal fibroblasts and the astroglial limiting membrane were seen. In addition a topographical correlation between the distribution of spinal cord veins and venules and demyelinated plaques was found. These observations indicate that spinal cord lesions in chronic relapsing EAE are initiated by perivenous inflammation in the parenchyma and the meninges. Plaque formation, especially in spinal cord surface lesions, is additionally enhanced by the entrapment of inflammatory cells in the fibrosed meninges. The exchange of macrophages through the glia-limiting membrane may be responsible for the more rapid debris removal in the spinal cord in comparison with brain lesions in chronic relapsing EAE.

Animals↗
PubMed1981

Relapsing experimental allergic encephalomyelitis induced with isolated myelin and with myelin basic protein plus myelin lipids.

To test the ability of different spinal cord fractions to reproduce the clinicopathological features of relapsing experimental allergic encephalomyelitis (R-EAE), groups of young guinea pigs were inoculated with: (1) spinal cord myelin; (2) delipidated myelin; (3) reconstituted myelin and (4) MBP plus myelin lipids. The four sets of antigens induced acute EAE in most of the animals tested. During an observation period of 18 months, only one clinical relapse was observed in animals sensitized with myelin and with MBP plus myelin lipids. Extensive CNS demyelination was found in relapsing animals injected with myelin. No demyelinated lesions were observed in non-relapsing animals. By contrast, half of the surviving guinea pigs injected with MBP plus myelin lipids had demyelinated lesions, irrespective of whether they relapsed or not. The inability of the spinal cord myelin fractions to fully reproduce the R-EAE model suggest that other non-myelin antigens may be involved in the pathogenesis of multiple relapses.

Animals↗