The central nervous system and the reinforcement of behavior.

Discusses findings on reward and drive processes, noting that an anatomical study of brain rewards revealed a relatively unified system. Experiments which help clarify the relations between brain-stimulated negative reinforcement or pain behavior are cited. It is hypothesized that 4 learning grids might project from the hypothalamus into places like the cerebellum, tectum, hippocampus, and neocortex. In these grids, rewarding messages would (1) directly augment the frequency of ongoing responses, (2) reinforce certain ongoing synaptic relations, or (3) be recorded in memory elements to serve in relation to remembered behavior patterns. These processes might occur redundantly or simultaneously. (47 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structure and functions of the macroglia in the central nervous system. Response to degenerative disorders

INTRODUCTION: Glial cells have been known for a long time. For many years they have been considered to be merely a support for the structure of nervous tissue. Our limited knowledge of these cells has been mainly due to different methodological problems which made it impossible to discover more about their origin and physiology. Now, however, thanks to the development of immunocytochemical techniques, it has been possible to determine their structure, and their function have been discovered thanks to the modern molecular biology techniques. Thus the importance of the glia in the nervous system, both in normal and in pathological conditions, is now realized. In recent years increasing interest has been shown in the functional role played by macroglia (astrocytes and oligodendrocytes). DEVELOPMENT: Although astrocytes and oligodendrocytes have been classified into different types, according to their morphology, these cells are functionally very heterogeneous depending on the microenvironment in which they are found. However, this is only a measure of the number of key processes in which they participate to the correct functionality of central nervous system. CONCLUSIONS: The diversity of processes in which astrocytes and oligodendrocytes are involved shows that these cells can respond in different ways to neurodegenerative situations, both normal and pathological, in order to maintain the structural integrity of cerebral tissue. Although the role played by oligodendrocytes is less well-known than that played by astrocytes, both cell types may be perfect targets for treatment of nervous system diseases, and also of the neurodegenerative changes due to ageing.     

Schizophrenia and central nervous system pathology.

The Rorschach protocols of 3 groups of patients, typical process schizophrenics, atypical or reactive schizophrenics, and schizophrenics with known central nervous system pathology were examined for incidence of Piotrowski's 10 signs of organic involvement. It was found that organic and process groups could not be distinguished from each other, but both of these groups showed significantly more subjects with at least five signs than did the reactive group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of adenosine in the central nervous system

Adenosine is one of the normal elements in body fluid including extracellular fluid within the CNS. Its normal level is 0.03-0.3 mumol/L. When ATP's metabolism loses balance, for example, during ischemia, the level of adenosine increases dramatically, may reach as much as 1000 times of the normal. Adenosine plays many physiological and pathological roles in CNS via its receptors. It is recognized as an inhibitory neuromodulator playing a neuroprotective role in CNS.     

Autoantibodies in central nervous system lupus

Central nervous system (CNS) involvement in patients with lupus remains both a diagnostic and a therapeutic challenge. The role of autoantibodies in the pathogenesis of CNS lupus and/or as markers for disease activity is reviewed. Doubt is cast on the value of measuring anti-neuronal antibodies. Those antibodies binding ribosomal-P protein antigens or certain phospholipids appear to have greater utility, although even in these cases there is no uniform agreement as to their precise role in CNS disease induction, or how well antibody levels reflect disease activity.     

Pediatric central nervous system tumors

Numerous collagenous structures must be reconstituted following injury to the skin in order to return function to this tissue. The basement membrane zone, vascular basement membranes, and the dense connective tissue of the dermis are examples of structures that contain a number of different collagen types and that may need replacement following injury. In addition, a scar is deposited at the site of damage in order to substitute for elements lost in the trauma and for elements that cannot be successfully replaced. Clearly, cells resident within the different compartments of the skin are able to synthesize and deposit collagen to reform these multiple structures. However, accumulating experimental evidence suggests that in addition to these resident cells, blood-borne cells may be responsible for the deposition of a portion of the newly synthesized collagen. Studies from this laboratory point to the activated monocyte as a potential source of collagen in the wound environment. Given the dynamics of the process, the hypothesis is proposed that during normal wound healing, the activated monocyte is a source of collagen essential for the rapid formation of a provisional matrix conducive for the subsequent formation of granulation tissue. Collagen synthesis also occurs by expanded populations of resident cells, under the influence of inflammatory cell-derived mediators, which results in the major accumulation of collagen during normal wound repair. However, if a chronic inflammatory state is initiated, the activated monocytes may remain in sufficient numbers to deposit collagen leading to a pathological lesion.     

Primary central nervous system lymphoma. A changeable tumor

We have previously shown that lymphocyte beta 2-adrenoceptors (AR) are under cyclical control of sex-steroid hormones with greater receptor density during the luteal phase of the menstrual cycle. It has also been postulated that abnormal cyclical regulation of beta 2-AR might be a possible mechanism for premenstrual asthma. The effects of exogenous female sex-steroid hormones on lymphocyte beta 2-AR function were studied in eight normal healthy females. They were evaluated at two successive menstrual cycles, during the follicular phase (day 1-6). They were randomized to receive single oral doses of either ethinyloestradiol 50 micrograms or medroxyprogesterone 10 mg in a cross-over study. Lymphocyte beta 2-AR parameters were evaluated at baseline (t0), 24 h (t24) and 72 h (t72) after ingestion. Baseline levels of progesterone and oestradiol were comparable on both cycles. Receptor density (Bmax) increased significantly (P < 0.01) from t0 after progesterone but not oestradiol at t 4: a 1.39-fold geometric mean difference (95% CI 0.96-2.00) between t24 vs t0. Receptor affinity (kd) and maximal cAMP response to isoprenaline (Emax) were not altered by either treatment. These results show that exogenous progesterone but not oestradiol, given during the follicular phase, significantly increased beta 2-AR. This, therefore, suggests that endogenous progesterone is probably responsible for previously observed increase in Bmax during the luteal phase of the female menstrual cycle. These findings may suggest possible therapeutic strategies for modulation of beta 2-AR in premenstrual asthma.     

ATV-related central nervous system injuries in Louisiana

All terrain vehicles (ATVs) have been associated with death and serious injury since their introduction into the marketplace. Fifteen cases of ATV-related brain and spinal cord injury reported to the Louisiana Central Nervous System Registry during 1995 were evaluated for severity, etiology, and outcome. Eleven (73%) of these injuries were sustained by persons under 18 years of age. Despite US Consumer Product Safety Commission and ATV manufacturer recommendations for age restrictions, ATVs continue to be popular recreational devices for children.     

Cytokine actions in the central nervous system

Cytokines and chemokines have been implicated in contributing to the initiation, propagation and regulation of immune and inflammatory responses. Also, these soluble mediators have important roles in contributing to a wide array of neurological diseases such as multiple sclerosis, AIDS Dementia Complex, stroke and Alzheimer's disease. Cytokines and chemokines are synthesized within the central nervous system by glial cells and neurons, and have modulatory functions on these same cells via interactions with specific cell-surface receptors. In this article, I will discuss the ability of glial cells and neurons to both respond to, and synthesize, a variety of cytokines. The emphasize will be on three select cytokines; interferon-gamma (IFN-gamma), a cytokine with predominantly proinflammatory effects; interleukin-6 (IL-6), a cytokine with both pro- and anti-inflammatory properties; and transforming growth factor-beta (TGF-beta), a cytokine with predominantly immunosuppressive actions. The significance of these cytokines to neurological diseases with an immunological component will be discussed.     

Kinesin family in murine central nervous system

In neuronal axons, various kinds of membranous components are transported along microtubules bidirectionally. However, only two kinds of mechanochemical motor proteins, kinesin and brain dynein, had been identified as transporters of membranous organelles in mammalian neurons. Recently, a series of genes that encode proteins closely related to kinesin heavy chain were identified in several organisms including Schizosaccharomyces pombe, Aspergillus niddulans, Saccharomyces cerevisiae, Caenorhabditus elegans, and Drosophila. Most of these members of the kinesin family are implicated in mechanisms of mitosis or meiosis. To address the mechanism of intracellular organelle transport at a molecular level, we have cloned and characterized five different members (KIF1-5), that encode the microtubule-associated motor domain homologous to kinesin heavy chain, in murine brain tissue. Homology analysis of amino acid sequence indicated that KIF1 and KIF5 are murine counterparts of unc104 and kinesin heavy chain, respectively, while KIF2, KIF3, and KIF4 are as yet unidentified new species. Complete amino acid sequence of KIF3 revealed that KIF3 consists of NH2-terminal motor domain, central alpha-helical rod domain, and COOH-terminal globular domain. Complete amino acid sequence of KIF2 revealed that KIF2 consists of NH2-terminal globular domain, central motor domain, and COOH-terminal alpha-helical rod domain. This is the first identification of the kinesin-related protein which has its motor domain at the central part in its primary structure. Northern blot analysis revealed that KIF1, KIF3, and KIF5 are expressed almost exclusively in murine brain, whereas KIF2 and KIF4 are expressed in brain as well as in other tissues. All these members of the kinesin family are expressed in the same type of neurons, and thus each one of them may transport its specific organelle in the murine central nervous system.     

Glutamate receptors in the central nervous system

A lot of clinical processes following excessive stimulation of glutamate receptors seem to participate in pathophysiology of numerous acute and chronic neurological disorders. The whole of these reactions has been named as "glutamate cascade", because of the central role of glutamate in initiation and intensification of these processes. In this article, classification of different types of glutamate receptors and several hypotheses concerning mechanisms of glutamate neurotoxic activity are presented. A wide variety of neurological diseases, which etiologies are more or less connected with glutamate toxicity are discussed. At last, the future perspectives for treatment by drugs which action is thought to be mediated through glutamate receptors are presented.     

Stem cells in the central nervous system

In the vertebrate central nervous system, multipotential cells have been identified in vitro and in vivo. Defined mitogens cause the proliferation of multipotential cells in vitro, the magnitude of which is sufficient to account for the number of cells in the brain. Factors that control the differentiation of fetal stem cells to neurons and glia have been defined in vitro, and multipotential cells with similar signaling logic can be cultured from the adult central nervous system. Transplanting cells to new sites emphasizes that neuroepithelial cells have the potential to integrate into many brain regions. These results focus attention on how information in external stimuli is translated into the number and types of differentiated cells in the brain. The development of therapies for the reconstruction of the diseased or injured brain will be guided by our understanding of the origin and stability of cell type in the central nervous system.     

The effects of interferon-gamma on the central nervous system

A 165bp DNA fragment derived from the 12 kDa subunit of Echinococcus granulosus antigen B (AgB), a major hydatid cyst fluid antigen was cloned in the pMa1-c2 expression vector. A 52 kDa maltose binding-AgB fusion protein (rAgB.MBP) was produced and inclusion bodies containing the fusion protein were solubilised in urea and affinity purified on an amylose-Sepharose 6B column. The immunogenicity of the purified recombinant antigen for IgG4 antibody detection was tested with human serum using immunoblotting, ELISA and dot-ELISA assays and compared to native AgB. Both recombinant and native AgB preparations were highly reactive for human IgG4 antibodies in serum of cystic echinococcus (CE) patients. Recombinant AgB.MBP (rAgB.MBP) showed approximately 65% sensitivity in detection of IgG4 serum antibodies by ELISA from confirmed CE patients. Cross-reactivity (33%) occurred with alveolar echinococcosis (E. multilocularis) sera but recombinant AgB showed no seroreactivity with sera from other helminth infections tested (schistosomsis, onchocercsis, cysticercosis) or from uninfected individuals residing in CE endemic or non-endemic regions. The serologic sensitivity (63%) for IgG4 antibodies of a native AgB fraction enriched from human hydatid cyst fluid was similar to that for recombinant AgB (65%) though specificity was slightly lower (81%). A dot-ELISA for detection of total IgG, incorporating the rAgB.MBP resulted in 74% sensitivity and 88% specificity for human CE and 93% sensitivity and 65% specificity for native AgB. Recombinant AgB is a potential replacement for native antigens currently being used and could provide a better standardised E. granulosus specific test for clinical confirmation for CE especially for IgG4 antibody detection which appears to be predominantly associated with advanced disease.     

The central nervous system and the lymphatic system. Lymphatic drainage of the cerebrospinal fluid

BACKGROUND: Recent evidence suggests that transient neurologic symptoms commonly follow lidocaine spinal anesthesia. However, information concerning factors that affect their occurrence is limited. Accordingly, to evaluate many potential risk factors, the authors undertook a prospective, multicenter, epidemiologic study. METHODS: On a voluntary basis, anesthetists at 15 participating centers forwarded a data sheet on patients who had spinal anesthesia to a research nurse blinded to the details of anesthesia and surgery. A subset was randomly selected for follow-up. The pressure [corrected] of transient neurologic symptoms, defined as leg or buttock pain, was the principal outcome variable. Logistic regression was used to control for potential confounders, and adjusted odds ratios and confidence intervals were used to estimate relative risk. RESULTS: During a 14-month period, 1,863 patients were studied, of whom 47% received lidocaine, 40% bupivacaine, and 13% tetracaine. Patients given lidocaine were at higher risk for symptoms compared with those receiving bupivacaine (relative risk, 5.1; 95% CI, 2.5 to 10.2) or tetracaine (relative risk, 3.2; 95% CI, 1.04 to 9.84). For patients who received lidocaine, the relative risk of transient neurologic symptoms was 2.6 (95% CI, 1.5 to 4.5) with the lithotomy position compared with other positions, 3.6 (95% CI, 1.9 to 6.8), for outpatients compared with inpatients, and 1.6 (95% CI, 1 to 2.5) for obese (body mass index >30) compared with nonobese patients. CONCLUSIONS: These results indicate that transient neurologic symptoms commonly follow lidocaine spinal anesthesia but are relatively uncommon with bupivacaine or tetracaine. The data identify lithotomy position and outpatient status as important risk factors in patients who receive lidocaine. Among other factors postulated to increase risk, obesity had an effect of borderline statistical significance, whereas age, sex, history of back pain, needle type, and lidocaine dose and concentration failed to affect risk.     

Uveitis and central nervous system vasculitis

The purpose of this double-blind study was to investigate the influence of adding a quercetin-containing supplement to the diet on plasma quercetin status, serum/platelet fatty acid levels and risk factors for heart disease. Healthy men and women with cholesterol levels of 4.0-7.2 mmol/L, consumed four capsules daily of either a quercetin-containing supplement (1.0 g quercetin/d) or rice flour placebo for 28 d. Quercetin intakes were approximately 50-fold greater than the dietary intakes associated with lower coronary heart disease mortality on the basis of epidemiologic studies. Subjects consuming quercetin-containing capsules had plasma quercetin concentrations approximately 23-fold higher than those of subjects consuming the control capsules. Quercetin supplementation did not modify serum total, LDL or HDL cholesterol or triglyceride levels. There were also no alterations of other cardiovascular disease or thrombogenic risk factors, including platelet aggregation, platelet thromboxane B2 production, blood pressure or resting heart rate. Furthermore, there was no effect on the levels of (n-6) or (n-3) polyunsaturated fatty acids in serum or platelet phospholipids. In conclusion, supplementation with quercetin-containing capsules markedly enhanced the plasma quercetin concentration but had no effect on other cardiovascular or thrombogenic risk factors.     

Remyelination of the central nervous system

The three typical stages in the clinical course of multiple sclerosis (relapse, persistent disability and progression) can be explained on the basis of inflammation, demyelination and failure of repair leading to axon degeneration and astrocytosis. Strategies are being evaluated for limiting the inflammatory process using immunological treatments and these may have unexpected dividends in promoting endogenous remyelination. Increasing knowledge on glial lineages and axon-glial interactions needed for stable myelination also offer the prospect for enhancing remyelination through growth factor therapy and cell implantation.