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Growth promoting and inhibitory effects of glial cells in the mammalian nervous system.

In the central nervous system (CNS) of mammals axonal regeneration is limited by two main factors: first, the low intrinsic regenerative potential of adult CNS neurons and second, inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth as well as some properties of so called "reactive astrocytes" contribute to the non-permissive of CNS tissue for axonal growth. In contrast, the peripheral nervous system (PNS) environment is supportive of regeneration because Schwann cells provide suitable substrates for regrowing axons. Purified PNS myelin, however, inhibits growth of PNS and CNS axons to a similar extent as does CNS myelin. The molecular basis of glial substrate properties has been studied intensively in the recent years and a large number of molecules have been recognized which might play a role in the regulation of axonal growth. Although the exact mechanisms are still not fully understood, accumulating data shed light on the complex interactions between neurons and glia that are required to establish, maintain, and regenerate axonal connections in the nervous system. In the following chapter we review the role of glial cells in the CNS and PNS during processes of de- and regeneration with respect to our own work.

Animals↗

[Inflammatory and infectious manifestations of the nervous system].

The Central Nervous System is the site of a wide variety of inflammatory and infectious diseases. Some disease entities have been in the focus of interest in recent years and progress has been achieved in our understanding of some chosen domains. We will review recent progress in our knowledge about transmissible spongiformes encephalopathies and AIDS-associated lesions, and briefly discuss cerebral vasculitis, granulomatous diseases and the most frequent infections by parasites.

AIDS Dementia Complex↗

Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus affecting the central nervous system.

A 22 year old woman with systemic lupus erythematosus affecting the central nervous system had acquired C1 inhibitor deficiency. She was admitted for treatment of psychotic behaviour, but showed no signs of angioedema. The serum complement profile of the patient showed normal C3 concentration and a depletion of C4, C2, C1 inhibitor, and C1q. Her parents had normal complement profiles. An extremely reduced C4 concentration may lead to involvement of the central nervous system in systemic lupus erythematosus.

Adult↗

The study of anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with systemic lupus erythematosus and central nervous system involvement.

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

Adolescent↗

Expression and localization of Na+/H+ exchangers in rat central nervous system.

Neurons in the central nervous system regulate their intracellular pH using particular membrane proteins of which two, namely the Na+-dependent Cl-/HCO3- exchanger and the Na+/H+ exchanger, are essential. In this study we examined messenger RNA expression and distribution of Na+/H+ exchanger in the newborn rat central nervous system and with maturation using Northern blot analysis and in situ hybridization. Our study clearly shows that each Na+/H+ exchanger has a different expression pattern in the rat central nervous system. As in non-excitable tissues, Na+/H+ exchanger 1 is by far the most abundant of all Na+/H+ exchangers in the rat central nervous system. Its expression is ubiquitous although its messenger RNA appears at higher levels in the hippocampus, in the 2nd/3rd layers of periamygdaloid cortex and in the cerebellum. The low level of messenger RNAs encoding Na+/H+ exchanger 2 and 4 is mainly expressed in the cerebral cortex and in the brainstem-diencephalon, while Na+/H+ exchanger 3 transcripts are found only in the cerebellar Purkinje cells. From a developmental point of view, Na+/H+ exchanger 1, 2 and 4 showed an increased level in their transcripts in the cerebral cortex while an opposite trend existed in the cerebellum from postnatal day 0 to postnatal day 30. The messenger RNA for Na+/H+ exchanger 3, however, increased its level with age in cerebellum. From our data we conclude that: i) the expression of the Na+/H+ exchanger is age-, region-, and subtype-specific, with Na+/H+ exchanger 1 being the most prevalent in the rat central nervous system; ii) specialization of groups of neurons with respect to the type of Na+/H+ exchanger is clearly illustrated by Na+/H+ exchanger 3 which is almost totally localized in cerebellar Purkinje cells; and iii) the developmental increase in the messenger RNA for Na+/H+ exchanger 1 in the cerebral cortex and hippocampus is consistent with our previous studies on intracellular pH physiology in neonatal and mature neurons. Together this study indicates that expression of each Na+/H+ exchanger messenger RNA is differentially regulated both during development and in the different regions of rat central nervous system.

Animals↗

Environmental effects on the central nervous system.

The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds.

Auditory Pathways↗

Genetic screen for mutations affecting development and function of the enteric nervous system.

An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies.

Animals↗

First and early second trimester diagnosis of anomalies of the central nervous system.

To study central nervous system development, 18 normally developing embryos or fetuses were examined sonographically between 6 and 16 weeks of pregnancy. Furthermore, in a 5 year period, 693 fetuses with an elevated risk for congenital defects were examined before 16 weeks of gestation. Abnormal development of the central nervous system was found in 28 fetuses. Early in pregnancy, normal central nervous system formation can be recognized, and pathologic cerebral development can be diagnosed already in the first trimester of pregnancy. We recommend routine use of safe and noninvasive transvaginal ultrasonography early in pregnancy for patients at risk.

Case-Control Studies↗

The impact of formal instruction in clinical examination skills on medical student performance -- the example of peripheral nervous system examination.

BACKGROUND: Peripheral nervous system examination is an essential part of the full medical clerking of a patient. We have investigated the effectiveness of formal instruction in peripheral nervous system examination compared to the traditional bedside ward teaching that our students usually receive. METHOD: We instructed an unselected group of 22 medical students in peripheral nervous system examination in a clinical skills centre and evaluated them with a 12 item marking schedule before and after instruction. The performance of this group was then compared to the rest of their year (220 students) in an end of year OSCE, which included a neurology station assessing sensory examination of the lower limbs. RESULTS: Students formally instructed in neurology significantly improved their scores after instruction and scored 15% higher marks (90% vs. 75%) than the rest of their year in the end of year neurology OSCE station 2 months later (P < 0.01, Mann Whitney U-test). They did not perform significantly better in the OSCE overall. CONCLUSIONS: Formal instruction in neurological examination resulted in a significant increase in the end of year neurology OSCE station score compared to traditional heterogeneous teaching methods.

Clinical Competence↗

Cerebral imaging by magnetic resonance imaging and single photon emission computed tomography in systemic lupus erythematosus with central nervous system involvement.

OBJECTIVE: To assess the significance of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) abnormalities in patients with systemic lupus erythematosus (SLE). METHODS: Forty-four patients with SLE were retrospectively analysed. Patients were classified into three groups [1 and 2: patients with central nervous system (CNS) manifestations before and after starting high-dose steroid therapy, respectively; 3: patients without CNS manifestations. MRI was performed in all 44 patients and SPECT in 31. RESULTS: Abnormal findings in MRI were found in 19 patients. MRI abnormalities were significantly more frequent in patients with CNS manifestations than in those without [71 vs 17%, odds ratio (OR) 11.9, confidence interval (CI) 2.8-49.9, P=0.0003]. After the initiation of steroid therapy, patients with CNS manifestations also had an increased frequency of abnormal MRI. No correlation was found between SPECT findings and CNS manifestations. However, patients with CNS manifestations after starting steroids showed a markedly increased frequency of abnormal MRI and SPECT compared with those without CNS manifestations (80 vs 7%; OR 56, CI 4.4-719, P=0.0003). The positive predictive value of abnormality in both techniques in developing CNS manifestations after starting steroids was 89%. CONCLUSION: MRI findings correlated with CNS manifestations in SLE. Where there is a high suspicion of CNS involvement, the combination of MRI and SPECT may be useful in predicting CNS manifestations after starting steroid therapy.

Adolescent↗

Trichobilharzia ocellata infections in its snail host Lymnaea stagnalis: an in vitro study showing direct and indirect effects on the snail internal defence system, via the host central nervous system.

In this in vitro study we investigated whether previously described in vivo plasma-associated effects, that occurred in the period shortly after penetration of Trichobilharzia ocellata into the snail host Lymnaea stagnalis (1.5-72 h post-exposure; p.e.) were direct and/or indirect effects of parasite-derived factor(s). It was investigated whether the effect is mediated by the central nervous system (CNS) of the host. Phagocytic activity of the haemocytes was taken as a parameter for the activity of internal defence of the host. A number of preliminary experiments were performed. When the supernatant of in vitro cultured parasites (33 h; corresponding with their developmental stage in vivo when plasma-associated activation was found) was applied directly to monolayers of haemocytes, it appeared to enhance their phagocytic activity. No direct effect, however, was found with a supernatant of parasites cultured for a longer period of time (72 h; when, in vivo, a plasma-associated suppression was found). In this case, indirect suppression was detected: the parasites appeared to have released a factor that induced the CNS of the host to release material suppressing the activity of the internal defence system of the host. To date the nature of this factor is unknown.

Animals↗

Central nervous system anomalies.

Fetal central nervous system abnormalities encompass a variety of lesions. Most of the anomalies are seen in association with an increased incidence of fetal aneuploidy and an increase in other anomalies both within and outside of the central nervous system. These associated findings and the underlying lesion all have a role in the eventual prognosis for the ongoing pregnancy. The antenatal diagnosis of a central nervous system abnormality should prompt a careful search for other defects, and consideration should be given for genetic evaluation and testing.

Diagnosis, Differential↗

Central nervous system mesenchymal chondrosarcoma.

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Adolescent↗

Cerebrospinal fluid anti-SSA autoantibodies in primary Sjogren's syndrome with central nervous system involvement.

BACKGROUND: Central nervous system involvement in primary Sjogren's syndrome is a matter of controversy, and its diagnosis remains difficult. METHODS: We report 3 patients with primary Sjogren's syndrome and central nervous system involvement in whom we assessed intrathecal immunoglobulin G synthesis and the presence of cerebrospinal fluid anti-SSA and anti-SSB autoantibodies. RESULTS: We found intrathecal immunoglobulin G synthesis and presence of cerebrospinal fluid anti-SSA autoantibodies in all patients, with demonstration for the first time of specific anti-SSA autoantibody intrathecal synthesis in 2 patients. CONCLUSION: We suggest that cerebrospinal fluid anti-SSA autoantibodies could serve as a biomarker for Sjogren's-syndrome-related central nervous system involvement.

Antibodies, Antinuclear↗

[The effect of alterations of the renin-angiotensin system and the sympathetic nervous system on plasma bradykinin concentration in patients with essential hypertension].

We studied the possible interplay between plasma bradykinin (P-BK) and the renin-angiotensin axis in essential hypertension, the effect of catecholamine on P-BK by standing and norepinephrine (NE) infusion, and the possible role of bradykinin in the hypotensive mechanism of angiotensin I converting enzyme inhibitor (captopril) in renin-independent essential hypertension. Plasma bradykinin was measured by sensitive radioimmunoassay in 44 hypertensive patients and compared with that of 24 normotensive subjects. P-BK was not significantly reduced in hypertensive patients, and when subjects were divided by age range, the P-BK was reduced by aging in normotensive subjects but not in hypertensive patients, and the elder (60 approximately 80 yr) age normotensive group showed significantly (p less than 0.05) lower P-BK compared with the elder hypertensive group. 28 essential hypertensive patients (EHT) who were classified as WHO stageI (n=15) and WHO stageII (n=13) were given 80 mg of furosemide orally and kept upright for 4 hours. Plasma renin activity (PRA), P-BK, plasma aldosterone (P-Ald) and serum angiotensin converting enzyme activity (ACEA) were measured before and after furosemide administration. Twelve normotensive subjects served as controls. PRA, P-Ald and ACEA showed a significant increase (p less than 0.05) in all groups in response to furosemide. In normotensives, basal P-BK was 11.1 +/- 1.3 pg/ml which increased to 15.6 +/- 1.8 pg/ml (p less than 0.02) after furosemide. These changes of P-BK were in parallel with PRA, P-Ald and ACEA. In the WHO stageI EHT group, baseline P-BK was 9.7 +/- 1.3 pg/ml which increased to 15.6 +/- 1.8 pg/ml (p less than 0.02) and PRA, P-Ald and ACEA showed a similar increase as in normotensives. In the WHO stageII EHT patients, however, P-BK showed only a slight increase from 9.8 +/- 1.0 pg/ml to 12.0 +/- 1.1 pg/ml after furosemide. These changes were smaller either than normotensives or the WHO stageI EHT group. There was a slight but significant correlation between PRA and P-BK in normotensives and in the WHO stageI EHT. There was no correlation between PRA and P-BK in the WHO stageII EHT. The present results do not support the view that there may be a direct linkage between the kallikrein kinin system and the renin angiotensin axis mediated by kininase II or angiotensin converting enzyme in human peripheral blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗