Acta neuropathologica. Supplementum最新文献

The present report, compares two murine models of virus induced chronic relapsing demyelination. MHV-induced demyelination in the BALB/c mouse results from the direct virus mediated cytolysis of oligodendrocytes. Extensive remyelination by oligodendrocytes is noted. Recurrent demyelination occurs in small areas. Infectious virus persists and viral antigens are localized within oligodendrocytes and their processes. TMEV-induced demyelination in SJL/J mice is associated with perivascular inflammatory infiltrates and is diminished by immunosuppressive measures. Remyelination by oligodendrocytes is delayed and incomplete. Chronic demyelination is widespread and associated with perivascular inflammatory infiltrates. The virus persists and viral antigen is localized within oligodendrocytes. The findings indicate virus persistence in oligodendrocytes in both models. Demyelination follows the disintegration of infected oligodendrocytes. Virus replication in oligodendrocytes is responsible for cell lysis in the MHV model whereas immune mediated injury of infected oligodendrocytes is considered to play a role in the pathogenesis of demyelination in the TMEV model.

The cytochemical localisation of five hydrolytic enzymes has been studied in the brain capillaries of laboratory animals. Acid phosphatase is present in primary lysosomes of endothelial cells; alkaline phosphatase activity is seen mainly on the plasma membrane of the luminal side but also in the basal lamina. The latter is also active concerning 5'nucleotidase. Butyrylcholinesterase is an enzyme synthesized by most brain capillary endothelial cells, as can be seen by intensive staining of endoplasmic reticulum cisternae. In contrast acetylcholinesterase activity at the capillaries presumably is of neuronal origin. Local neurons appear to secrete this enzyme, which then reaches the endothelial basal lamina via the extracellular spaces. From these cytochemical observations it is concluded that pinocytotic traffic in brain endothelial cells is predominantly from the brain tissue side to the luminal side.

Hydrophilic substrates necessary for brain function cross the capillary by facilitated diffusion. The facilitation has many features in common with enzyme-catalyzed reactions and is probably subserved by protein entities in the endothelial wall. The proteins act as receptors, recognizing substrate molecules, and as translocators, giving the molecules access to an aqueous path through the endothelium. These receptor-translocators can be saturated, and the transport is subject to competitive inhibition by substrate analogs. Thus, amino acids inhibit the transport of each other, and galactose can inhibit glucose transport in suckling rats. The proteins can be induced, as in the case of ketone transport in starvation, and repressed, as in the case of glucose transport in hyperglycemia. In rats with hyperglycemia for three weeks, the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 mumol/hg/min. An important result of the description is the understanding that rigid distinctions between the function of receptors, translocators, and enzymes is impossible. Understanding of the biochemical properties of facilitated diffusion may help explain a variety of symptoms in many 'inborn errors of metabolism'. This understanding has followed greater, recent insights into the general properties of the blood-brain barrier (45,46,47).

Probably, the most important evidence concerning the breakdown of the BBB is a large inflow of hematogenous fluid into the extravascular spaces. Thus all parenchymal cell elements represent freely floating cells in this fluid medium called the edema fluid. These essential morphological alterations, such as extremely expanded extracellular space and freely floating cells within the fluid, were also observed in the developing normal fetal brain. Many neuroblasts were vigorously migrating in the fetal brain, as were the macrophages and reactive astrocytes in the edema fluid. Obviously, hematogenous cells and reactive astrocytes in the edematous lesion take part in its repair. Many astrocytes, GFAP positive, in the 3 or 4 day-old lesions, revealed mitosis. And in vitro, when we immersed these astrocytes in the protein and glucose rich medium, they demonstrated a remarkably changed morphology and were moved into the M and G1 phases, thus gaining the ability of cell motility. This was also true in the edema fluid. Brain edema is definitely a serious "pathological" condition. But it is also conceivable from a different biological aspect that as a result of BBB "opening", free extracellular space essential for cell motility and a source of their energy is ingeniously provided for these cells, and thus the lesion can be effectively repaired. The biological significance of the edema fluid was emphasized and stereotaxic morphology and cinematography, supporting the above evidence, have also been presented.

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.

The morphological features of the blood-brain barrier to macro-molecules under normal and perturbed conditions are reviewed in the context of some recent investigations. The electric charge on molecules of horseradish peroxidase (HRP) affect its pinocytosis and intracellular fate which pertains to problems of distinguishing endocytosis from vesicular transport across endothelium. When the barrier is opened, the number of pits, vesicles and tubules increases. Such cerebral endothelium resembles normal endothelium of certain fish where numerous membrane invaginations do not signify vesicular or tubular transport. However, such transport has not been entirely ruled out in reactive endothelium. Another route of exudation during barrier opening may be via patent endothelial junctions, especially during intravascular infusion of hyperosmotic solutions. The permeability of the tight junctions, however, is not reflected unequivocally by its intramembranous structure. Although astrocytes do not provide a barrier to the extracellular flow of solutes, their ubiquity may enable them to modify the composition of perineuronal fluid. Their orthogonal arrays of intramembranous particles may be involved. The number of assemblies increases in astrocytes reacting to trauma and to the extracellular accumulation of lactate and CO2. The assemblies might thus participate in the transport of catabolites to and from extracellular fluid.