[ON THE DETERMINATION OF THE EQUILIBRIUM OF BASIC NERVOUS PROCESSES IN DOGS WITH DIFFERENT TYPES OF THE NERVOUS SYSTEM].
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A study was made of the uptake of horseradish peroxidase (HRP) into neurons from a cryogenic cortical lesion in the mouse brain associated with vasogenic edema, following intravenous administration of the tracer. Particular emphasis was placed on the axonal spread of HRP from the primary lesion to other areas of the central nervous system. The distribution of HRP was studied by light microscopy, using highly sensitive histochemical methods, 3-144 h after the onset of the injury. Extravasated HRP was taken up into nerve cell bodies in and around the primary lesion, forming different patterns of labelling: (1) granular, (2) diffuse, and (3) a combination of granular and diffuse staining. Granularity is considered to be the result of HRP accumulation in lysosomes occurring in undamaged or slightly damaged nerve cells, whereas the diffuse, non-granular pattern presumably occurs in severely damaged neurons. Nerve cell bodies containing HRP reaction product were also found in the contralateral cortex, ipsilateral thalamus, substantia nigra, amygdala and ventral tegmental area, presumably a consequence of retrograde axonal transport of the tracer from the primary injury. HRP-containing axons were present in the corpus callosum and in the pyramidal tract of the injured hemisphere all the way down to the cervical spinal cord. Labelling of axonal terminals and preterminal axons in the ipsilateral thalamus, entopeduncular nucleus, subthalamic nucleus, substantia nigra and pons indicated anterograde transport of HRP to these regions. Thus very extensive intraneuronal spread of a macromolecular edema component takes place from a primary focal brain lesion to areas located far away from but neuroanatomically connected to this injured region. The brain thus seems to be affected by focal vasogenic edema in many more ways than are recognized at present.
There is an "emerging concept" that central nervous system dysfunction can be caused by an aberrant immune response triggered by exogenous antigens such as the food allergen gluten or streptococcal infection. The hypothesis of a gluten sensitive ataxia remains unproven, but is worthy of consideration. The data in support of this hypothesis require critical review before any treatment recommendations can be formulated. The idea that anti-gliadin antibody seropositivity per se justifies the term "gluten sensitivity" is important because it offers potential therapeutic possibilities, including simple exclusion diets, for patients with anti-gliadin antibody-associated ataxia. Post-streptococcal basal ganglia dysfunction has various manifestations, all of which fall into a relatively well-defined symptom complex or syndrome. Anti-basal ganglia antibodies that are associated with serologic evidence of recent streptococcal infection are a potential diagnostic marker for this group of disorders, which includes Sydenham's chorea (SC) as the prototype. More recently subjects with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, Tourette's syndrome, obsessive-compulsive disorder and other movement disorders have been described in association with anti-basal ganglia antibodies. The apparent overlap between the clinical phenotype of SC, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, Tourette's syndrome, and obsessive-compulsive disorder suggests that they may represent one disease entity. The current working hypothesis is that antibodies induced in response to streptococcal infection cross-react with antigenic determinants in the basal ganglia resulting in basal ganglia dysfunction. Although the experimental evidence is incomplete, there is sufficient evidence to support immune-mediated basal ganglia dysfunction as an emerging clinical entity. This has important implications for the diagnosis and treatment of subjects with these disorders. The latter includes the judicious use of antibiotic prophylaxis and immunomodulatory therapies. Apart from the diagnosis and management of SC, no consensus exists regarding the diagnosis and management of the other clinical entities within this group of disorders.
OBJECTIVE: HIV-1 encephalopathy (HIVE) is associated with high levels of viral RNA in the central nervous system (CNS). Highly active antiretroviral therapy (HAART) effectively reduces HIV replication in both plasma and cerebrospinal fluid (CSF). Some individuals, however, exhibit delayed CSF HIV RNA suppression in the presence of rapid plasma responses. We investigated the reasons for this discrepancy. DESIGN: CSF and plasma were collected prospectively in paired samples before and once or several times during HAART in 40 HIV-positive subjects. Ten had HIVE and 30 patients were neurologically asymptomatic or had non-HIVE neurological manifestations. METHODS: The slopes of viral RNA decay during HAART were compared between the compartments. The presence of HIVE was defined by clinical standards and its severity categorized according to the Memorial Sloan Kettering score. CSF and plasma levels of antiretroviral drugs were measured. Viral drug resistance during HAART in CSF and plasma was analysed both genotypically and phenotypically. RESULTS: Slow CSF viral decay and a high degree of compartmental discordance (slopeCSF/slopeplasma) were both significantly correlated with HIVE (P < 0.00002). There was no correlation of a rapid CSF response with Centers for Disease Control and Prevention stage, CD4 cell count, or with the number of antiretroviral compounds and their known CSF penetration. Slow CSF viral decay was associated with neither low levels of antiretroviral drugs in the CSF or plasma, nor with viral drug resistance. CONCLUSIONS: None of the treatment-associated variables, but only the presence of HIVE, was associated with delayed virus elimination during HAART in the CSF. This suggests a distinct pattern of viral replication in the CNS in HIVE.
Pigs were used for studies of effects on the peripheral nervous tissue of pressure waves induced by impact and passage through the left thigh of high-energy missiles. The short-lasting pressure waves were demonstrated to move close to the speed of sound and to have a spectrum of high frequencies and large amplitudes. The sciatic nerve in the contralateral leg showed no hemorrhage or major deformation. Both immediately after the missile impact and after 48 hr the myelin sheaths in the contralateral sciatic nerve showed deformation. Myelin was bulging into the axon, dislocating the axoplasm. The nodes of Ranvier could be exposed to an increased extent. Electron microscopic examination revealed decreased number of microtubules immediately after the trauma, persisting even after 48 hr in the largest axon. Schwann cells showed, especially after 48 hr, signs of damage and swelling. Similar changes, although less extensive, were noticed in the phrenic nerves as well as in unmyelinated axons in both sciatic and phrenic nerves. It is concluded that a high-energy missile hit in the thigh of a pig, caused structurally demonstrable dislocations of myelin sheaths, and disarrangement of cytoskeleton and endoplasmic reticulum in axons as well as other signs of damage. The changes may interfere with the normal functions of peripheral and autonomic nerves.
Radioiodinated lectins were used to detect glycoproteins of peripheral nervous system (PNS) myelin (rat, human, bovine) and cultured rat Schwann cells. Proteins were resolved by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and transferred to nitrocellulose filters. The filters were overlaid with radioiodinated lectins of known saccharide affinities. These included concanavalin A, Helix pomatia, Limulus polyphemus, Maclura pomifera, peanut, soybean, Ulex europaeus, and wheat germ agglutinins. Inclusion of the appropriate monosaccharide in the overlay solution (0.2 M) inhibited lectin binding to the nitrocellulose-fixed proteins. Fluorography permitted identification of 26 myelin glycoproteins and many more in Schwann cells. All lectins labeled a band present in myelin, but not Schwann cells, corresponding to the major PNS myelin protein, P0. Our attention focused on a high-molecular-weight myelin glycoprotein [apparent molecular weight (Mr) 170,000], which appeared abundant by Coomassie Blue staining and which was heavily labeled by all lectins except concanavalin A. A protein with approximately this Mr and lectin-binding pattern was present in human and bovine PNS myelin as well, but not detected in rat Schwann cells, CNS myelin, liver and fibroblast homogenates, or cultured bovine oligodendroglia. Hence this 170,000 Mr glycoprotein is apparently unique to PNS myelin.
We recently characterized two developmentally regulated myelin-associated glycoprotein (MAG) polypeptides synthesized by mouse brain mRNA in vitro. We now extended these studies to include the peripheral nervous system (PNS). Total cytoplasmic RNA was isolated from the sciatic nerves of 7-, 12-, and 17-day-old and adult rats and translated in vitro in a rabbit reticulocyte lysate system. In contrast to results in the CNS, it appears that only one MAG polypeptide, p67MAG, is synthesized by PNS mRNA at all ages. The implications of these findings are discussed with respect to recent observations concerning both the localization of MAG and the synthesis of MAG in the PNS of dysmyelinating mutant mice.
The problem of the differential diagnosis both of central nervous system haemangioblastomas and metastases of renal clear cell carcinomas was investigated by immunoperoxidase labelled antibody staining of five cases each of haemangioblastoma and metastatic renal carcinoma. Staining using anticarcinoembryonic antigen (CEA), antikeratin, antifactor VIII related antigen, and antibrush border was unhelpful. All five of the haemangioblastomas were negative and all five of the metastases were positive for epithelial membrane antigen (EMA), as defined by immunoperoxidase staining. This shows that commercially available anti-EMA monoclonal antibody is useful in distinguishing the two pathological entities.
Following the injection of central nervous system (CNS) cell cultures, prepared from 1-day-old rats and maintained in vitro for 7 days, into irradiated, demyelinating lesions in the spinal cord of adult isologous animals, extensive remyelination of axons by oligodendrocytes was observed. In addition, astrocytes, within the transplanted cell suspension, established normal relationships with oligodendrocytes, axons and other tissue elements, which led to the establishment of large CNS territories throughout the lesions. Outside these CNS domains, Schwann cells, which are present in the transplanted cell suspension, myelinated groups of axons. These observations indicate that the irradiated, ethidium bromide lesion provides an in vivo environment, devoid of the influences of host glia, in which to examine the interactions of transplanted glial cells with demyelinating axons.
We examined the role of tumor necrosis factor receptor 1 (TNFR1) in inflammation initiated by the adoptive transfer of central nervous system (CNS)-specific Th1 cells in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. This adoptive transfer paradigm eliminates the confounding effects of bacterial adjuvants in the analysis of inflammation. We found that although T cells could reach the meninges and perivascular space in the absence of TNFR1, recruitment of other inflammatory cells from the blood was dramatically reduced. The reduction in the recruitment of CD11b(hi) cells correlated with a dramatic reduction in the production of the chemokines CCL2 (MCP-1) and CXLC2 (MIP-2) in TNFR1-deficient hosts. Bone marrow chimera experiments demonstrated that TNF can be effectively supplied by either the hematopoietic system or the CNS, but the essential TNFR1-responsive cells reside in the CNS. Previous work has demonstrated that microglia produce CCL2, and here we demonstrate that astrocytes and endothelial cells produced CXCL2 in the early stages of inflammation. Therefore, productive inflammation results from a conversation, or mutually responding signals, between the initiating T cells and cells in the parenchyma of the spinal cord.
The paper presents the results of somatic, neurologic and neurophysiologic examination of 614 children which had hypoxic-ischemic encephalopathy of a moderate degree during the period from the birth till 3 years old. A period of gestation was characterised by some signs of fetoplacental insufficiency in 44.3% of children. Disorders in labor activity were revealed in 83.7% of mothers. Delay in nervous-mental development (77.3%), deviations in forming rhythmic EEG activity (75%), signs of morphologic immaturity of brain (38.8%) testified to inhibition of postnatal neuroontogenesis. All that together with high frequency of motor disorders (73.3%) and disorders in cerebral blood flow (43.8%) during the 1-st year of life were found to underlie development of psychoneurologic diseases in children of early age and necessitates early rehabilitation of these children.
We report two cases of central nervous system (CNS) metastases during systemic response to trastuzumab in combination with chemotherapy for refractory breast cancer. The patients responded to trastuzumab in combination with chemotherapy. During combination treatment, the patients developed cerebellar metastases. A follow-up computed tomography scan revealed that their diseases continued to respond outside the CNS. These cases suggest that the failure of trastuzumab to cross the blood-brain barrier may compromise its overall effectiveness and raises the possibility that CNS metastasis may become clinically more significant in patients receiving antibody-based therapies, including patients responding to therapy outside the CNS. Additionally, repeated stereotactic radiosurgery as gammaknife combination therapy synchronously with systematic trastuzumab-based therapy was useful for the treatment of metastatic breast carcinoma.
In 15 healthy subjects we stimulated the peripheral nervous system by a brief intense magnetic field and recorded evoked muscle potentials from peripheral muscles. Latencies were compared with those obtained by conventional electrical stimulation techniques. Amplitudes of muscle responses after magnetic stimulation were often smaller than those obtained after electrical stimulation; however, latencies were comparable at all stimulation sites.
A simple and yet reliable technique of silver impregnation for demonstrating nerve fibers in frozen sections of the human central nervous system is described. The following procedure is recommended. Frozen sections 10-25 micrometers thick, 5% aqueous solution of potassium ferricyanide for 2 h (37 degrees C), 10% aqueous solution of silver nitrate for about one h (37 degrees C) or until sections obtain a light brown tint, ammoniacal silver solution, reduction in 20% formalin, gold toning dehydrating and mounting. By this procedure, fine fibers display a color range from purple to dark purple on an almost colorless background. Gold treatment may be omitted. The technique described here is compared and discussed with an earlier technique using potassium ferrocyanide (Ogawa 1979).
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