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Biomedical subjects

M B Bornstein

Publications and source records attributed to M B Bornstein.

At least 73 records · Page 4Linked to original sources
PubMed1978

Disorganization of myelinogenesis in tissue culture by anti-CNS antiserum.

The presence of decomplemented anti-CNS antiserum profoundly affects myelinogenesis in cultured mouse embryo spinal cord. Light and electron microscope study has shown that oligodendroglia differentiate and produce an abundance of cell processes which surround the oligodendrocytes in a chaotic, disorganized array. Where the cell processes chance to meet, they form a kind of aberrant swollen myelin. Rarely, the oligodendroglial processes ensheath axons. For the most part, the available axons remain unmyelinated. On removal of the decomplemented antiserum, oligodendroglia differentiate and form normal myelin around the available axons. Myelination of peripheral nervous system (dorsal root ganglion) axons in the same preparations is unaffected by the presence of the antiserum. Thus, under these circumstances, the message from the neuron to the oligodendrocyte to make myelin is apparently intact, yet there is interference with the ability of the oligodendroglial cell process to find, attach to and encircle CNS axons with a normal myelin sheath.

Animals↗
PubMed1978

Antiserum-induced dissociation of myelinogenesis in vitro. An ultrastructural study.

Mature, myelinated cultures of mouse spinal cord tissue exposed to heated (decomplemented) sera from animals suffering from experimental allergic encephalomyelitis demonstrate a unique pattern of myelin swelling without demyelination. In the present study, three concentrations of heated experimental allergic encephalomyelitis sera (5, 15, and 25 per cent) were applied to spinal cord cultures from the time of explantation and continued for 33 days therafter. The sera were obtained from rabbits with the exposed cultures, glial cell differentiation occurred at timepoints comparable to those in normal unexposed sister cultures. Oligodendroglia produced a profusion of cytoplasmic processes which compacted to form aberrant myelin with a periodicity double that of normal myelin, containing four leaflets in the position of the normally bilamellar intraperiod line. The degree of the oligodendroglial abnormality was dose dependent, 25 per cent heated experimental allergic encephalomyelitis serum being the most potent. Frequently, in older cultures, large diameter axons, which under normal circumstances would have been well myelinated, were devoid of myelin sheaths although abundant aberrant myelin could be seen around nearby oligodendroglial cells. Rarely similar aberrant myelin was deposited around axons. It appeared, therefore, that the oligodendroglial cells had proliferated myelin which was unable to reach axons, possibly reflecting a failure in recognition between the two.

Animals↗
PubMed1977

Immunocytochemical studies for the localisation of measles antigens in multiple sclerosis plaques and measles virus-infected CNS tissue.

Actively demyelinating central nervous system (CNS) lesions from a patient with acute multiple sclerosis (MS) were tested for measles antigens using peroxidase-conjugated antimeasles antibody. No evidence of measles antigens was found. Similarly reacted tissue from 2 patients with chronic MS also revealed no evidence of measles antigens. Identically treated and simultaneously tested measles-infected CNS cultures and human SSPE brain tissue stained strongly for measles antigens. The possible reasons underlying the failure to detect measles antigens in MS are discussed.

Adult↗
PubMed1977

Suppression of acute and chronic experimental allergic encephalomyelitis in Strain 13 guinea pigs. A clinical and pathological study.

Adult inbred Strain 13 guinea pigs develop an acute, fatal form of experimental allergic encephalomyelitis (EAE) about 2 weeks after a single injection of isologous spinal cord in complete Freund's adjuvant (CFA), but similarly injected juveniles develop a delayed, rarely fatal chronic form. Thirty-seven sensitised adult Strain 13 animals were separated into 2 groups. One group was permitted to develop acute EAE. The other group was injected intramuscularly with 1 mg of guinea pig or bovine myelin basic protein (MBP) in incomplete Freund's adjuvant (IFA) on day 2, 7 or 10 post-inoculation (PI) followed by 0.2 mg in IFA every third day for a total of 10 doses. Animals in the unsuppressed group succumbed to acute EAE 13-16 days post-sensitisation. No animal in the suppressed group died during this period. Animals treated with MBP beginning 2 days PI showed no clinical signs, but mild clinical manifestations occurred in animals suppressed from days 7 and 10 PI. These signs remitted by 21 days post-sensitisation. One suppressed animal (out of 21) died during the fourth week postsensitisation. The other 20 suppressed animals appeared clinically normal towards the end of the course of MBP injections and remained so for the 6 months of study. Morphological examination revealed that CNS lesions occurred in all animals. In animals suppressed with MBP beginning on day 2 PI, lesions consisted only of a few meningeal inflammatory cells. Animals given MBP beginning on day 7 or 10 PI and sampled 1-2 weeks later, had lesions which could not be distinguished from those occurring in the non-suppressed acute EAE group. In time, the suppressed animals developed lesions which were typical of chronic EAE with remyelination as a predominant feature. Preliminary experiments on the suppression of chronic EAE in 5 juvenile Strain 13 guinea pigs have revealed that 3 MBP-injected animals failed to develop clinical disease over a 28-week period of study although lesions typical of chronic EAE were present. Simultaneously, 2 non-suppressed juvenile animals developed clinical signs by 12 weeks. These were associated with both acute inflammation and demyelination superimposed upon regions of chronic demyelinative activity.

Acute Disease↗
PubMed1977

Tissue culture studies of possible uremic neurotoxins: myoinositol.

Organotypic cultures of dorsal root ganglion cells revealed neuronal toxicity when exposed to myoinositol at doses of 1090 to 109 micrometer (500 to 50 microgram/ml). The ultrastructural changes consisted of membranous cytoplasmic bodies at high concentrations and dense bodies at lower concentrations. There were no changes at 0 to 22 micrometer (0 to 10 microgram/ml). This range of neurotoxicity parallels the levels of myoinositol found in the serum of uremic patients. Myelin loss occurred in a pattern suggesting "secondary demyelination," similar to the pattern seen in uremic neuropathy. The relevance as a possible model for uremic neuropathy is discussed.

Animals↗
PubMed1976

The effects of measles virus and various strains of SSPE virus on organotypic cultures of nervous tissue.

The neurotropic effects, virologic behaviors and morphologic appearances of 4 strains of subacute sclerosing panencephalitis (SSPE) virus have been examined in organotypic cultures of hamster cerebellar tissue and have been compared with the Edmonston strain of measles virus in the same system. While measles virus caused extensive damage to nervous tissue, the SSPE strains, in general, exerted a less deleterious effect. All of the SSPE viruses replicated in this tissue. The SSPE strains showed morphologic variation ranging from normal measles-type virions to apparently nucleocapsid deficient forms. It is speculated that some of these differences between measles and SSPE virus may account for the differences in the in vivo conditions with which they are associated.

Animals↗
PubMed1976

Electrophysiological studies of fetal mouse olifactory bulb explants during development of synaptic functions in culture.

Explants of 18- or 19-day fetal mouse olfactory bulb have been maintained in culture for periods up to 5 weeks. Compound action potentials can be evoked in the bulb explants by 1 day in vitro, and by 3-4 days, synaptically mediated slow wave discharges can be domonstrated in bicuculline (10(-5) m). The capability of the bulb explants to generate these slow-wave discharges has also been revealed by the introduction of picrotoxin (10(-5)m, d-tubocurarine (10(-4)m) and chloride-free medium, but not of strychnine (up to 3 X 10(-5)M. The data indicate early functional development of inhibitory, as well as excitatory, synaptic systems. In addition, the selective and reversible depression of these slow wave potentials by GABA (1-5 X 10(-4)M), but not by glycine (up to 3 X 10(-3)M), indicates a GABA-ergic component in the inhibitory network. Single unit extracellular recordings have been obtained from the presumptive mitral cells which, in culture, are spontaneously active even as early as 1-2 days after explantation. Correlative Bodian silver-impregnations demonstrate the presence of neurons in these explants which resemble typical mitral cells. Studies of mitral cells using paired stimuli suggest the development in vitro of an inhibitory system analogous to that known to suppress the excitability of their in situ counterparts following orthodromic or antidromic activation. These data, as well as the pharmacological sensitivities of the mitral cells in culture to GABA (5 X 10(-4)M) and bicuculline (10(-5)M), indicate that granule-to-mitral synapses may develop characteristic functions in olfactory bulb explants.

Action Potentials↗
PubMed1976

The initial structural lesion in serum-induced demyelination in vitro.

Myelinated cultures of mouse spinal cord were exposed to sera obtained from rabbits affected by experimental allergic encephalomyelitis following challenge with whole white matter in complete Freund's adjuvant. In the presence of complement, the tissue response begins with an increased birefringence of its myelin sheaths. This is rapidly followed by a gamut of changes leading to demyelination. This study reports that, in the absence of complement, the response is arrested at the stage of increased birefringence. In this way, this early stage of the demyelinating process was available for detailed examination by light and electron microscopy. The brightened myelin sheaths appeared with a few hours of exposure and were seen around all axons and sometimes around cell bodies. This was often accompanied by abrupt breaks in the sheaths and angularly shaped myelin figures. Examination by electron microscope revealed a uniform increase in the myelin period from 11 nm. to 22 nm. The normally double intraperiod line was increased to four electron-dense leaflets, the additional two appearing to be derived from the close apposition of an additional electron-dense layer on the outer surface of the myelin sheath or oligodendrocytic membrane. Oligondendrocytes responsed with a prolific growth of processes whose membranes compacted to form swollen myelin. Neurons, astrocytes, and neuropil showed no changes. In its early stages, at least, the swelling was reversible. It would appear, therefore, that we have isolated the first stage of antiserum-induced demyelination in vitro, a stage which is now available for further study.

Animals↗
PubMed1975

Effect of hypocholesterolemic drug AY9944 on cultured nervous tissue: morphologic and biochemical studies.

The effects of different concentrations of the hypocholesterolemic drug AY9944, an inhibitor of delta7-reductase, on organotypic cultures of fetal mouse spinal cord, were studied by light and electron microscopy. Exposure to 10(-6)M produced no observable changes. After 6 hours exposure to 10(-4)M, dense membrane-bound inclusions were occasionally observed in neurons. After 24 hours exposure to 10(-4)M, numerous cytoplasmic inclusions occurred in neurons, glia and macrophages. The form of these inclusions varied but were predominantly of two types; concentric, loosely-packed lamellae resembling membranous cytoplasmic bodies (MCB) of Tay-Sachs disease and irregular dense bodies. They were identical to those observed in our previous in vivo study. Prolonged exposure to the drug at 10(-4)M caused an increased number of inclusions in all cell types. Eventually the cultures degenerated. The number of inclusions increased for at least 38 days following a 2-5 day exposure to AY9944 at 10(-4)M. However, by 70 days, although inclusions persisted, the cultures were mostly astrocytic. In long-term cultures, in addition to these inclusions, curved or straight electron-dense paired profiles were seen in some cells, presumably macrophages. Biochemical analysis of cultures exposed to 10(-4)M revealed the continuous presence of delta7, 24-cholesta-diene-3beta-ol and 7-dehydrocholesterol even after the drug wa removed from the cultures. In our previous animal experiments, intracytoplasmic inclusions and abnormal sterols with a double bond at the 7 position disappeared quickly after discontinuation of the drug. Therefore, the results obtained in our present in vitro experiments are different in this regard from the in vivo studies of AY9944.

Cholestadienols↗