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.     

Astrocytic and neuronal factors affecting axon regeneration in the damaged central nervous system

Whether an axon will regenerate after it is cut depends on the balance between the intrinisic ability of the axon to regrow and the permissiveness of the environment surrounding it. The permissiveness of the environment is determined by the glial cells at the site of injury, and in the CNS both oligodendrocytes and astrocytes produce inhibitory molecules. Neurones differ greatly in the ability of their axons to regrow following axotomy. This intrinsic growth ability is greater in embryonic than adult neurones, varies from one neuronal type to another, depends on whether the axon is cut close to or far from the cell body, and can be increased by appropriate neurotrophic molecules.     

Neurotrophins and the primate central nervous system: a minireview

The central nervous system (CNS) of primates is more complex than the CNS of other mammals. Details of the development and aging of the primate CNS have recently been revealed by various neurobiological techniques. It has become clear that the primate CNS has unique characteristics, for example, the capacity for the overproduction and elimination of fibers and synapses. Some differences have also been found in the distribution of and changes with development in levels of various neuroactive substances. Recent discoveries of a variety of neurotrophins in the mammalian CNS have led to research on the neurobiology of these molecules in the primate CNS. The distribution of and changes with development in levels of nerve growth factor (NGF) in the primate CNS are closely correlated with the cholinergic system of the basal forebrain. The administration of NGF into the monkey brain prevents the degeneration of the cholinergic neurons of the basal forebrain after axotomy, a result that suggests that neurotrophins might be very valuable agents for the future treatment of neurological diseases, such as Alzheimer's and Parkinson's diseases.     

Virus-cell interactions in the nervous system and the role of the immune response

The outcome of a viral infection within the nervous system depends on a complex interplay between the virus, its target cell and the immune system. Recent research has elucidated a variety of mechanisms involved in these interactions and their role in the production of disease.     

Distribution and role of aspartate in the nervous system of the chaetognath Sagitta

Forty-nine female workers in the shoemaking industry, exposed to a solvent mixture containing benzene and twenty-seven non-exposed controls, were investigated. Concentrations of benzene and toluene in the working atmosphere, as well as benzene and toluene in blood and phenols in pre- and post-shift urine as parameters of biological monitoring, were determined. In order to assess hematotoxic risk, a complete blood cell count with differential, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, reticulocytes, serum iron, alkaline phosphatase in neutrophils and red blood cell glycerol lysis time were determined in all subjects. Benzene concentrations in the workplace atmosphere at the shoemaking factory ranged from 1.9 to 14.8 ppm (median = 5.9). Significant difference in benzene in blood (p = 0.005) and phenol in post-shift urine (p = 0.003) between exposed workers and controls confirmed exposure to benzene. Hemoglobin level (p = 0.02) and mean corpuscular hemoglobin concentration (p = 0.0002) in the shoe workers were lower, and band neutrophils (p = 0.005) and mean corpuscular volume (p = 0.03) higher, than in controls. Red blood cell glycerol lysis time was significantly higher (p = 0.000001) in shoe workers (X +/- SD = 41.6 +/- 8.9) than in controls (X +/- SD = 31.1 +/- 6.5) and showed a significant correlation with exposure biomarkers. The results confirm that benzene exposure below 15 ppm may produce qualitative abnormalities, particularly macroerythrocytosis and increased red cell glycerol resistance, in the absence of an overt quantitative decrease in circulating blood cells. Increased resistance to the hemolytic action of glycerol is a potentially useful biological monitoring procedure in medical surveillance of benzene exposed workers. The results of this study suggest that potential threshold concentration for hematologic effects of benzene is lower than 15 ppm.     

Genetic therapy for the nervous system: a trend in modern neurology

INTRODUCTION: Genetic therapy is in itself a new type of treatment, of potential use in many neurological conditions currently considered to be resistant to conventional treatment. Great advances have been made in the construction of vectors of expression and carriers of viral genes, thus work is starting on the characterization of target cells for neuronal genetic therapy. DEVELOPMENT: As a result of advances in this field, two methods of genetic transference have evolved. One, 'in vivo', involves transfection of genetic material by means of chemical or viral agents. The 'ex vivo' variant depends on manipulation of culture cells to subsequently inject them into the host organism with a view to correcting the cell phenotype. Both methods have been used in preliminary experiments designed to test the efficacy of genetic transference for improvement of dysfunction of the nervous system. At the present time there is much experimentation with the use of genetic transference using modified cells to synthetize growth factors or key enzymes of the neurotransmission process in biomodels of Parkinsonism and Alzheimer amongst other conditions. CONCLUSIONS: Genetic therapy, as is shown in this review, has great therapeutic potential for nervous diseases which are very severe and complex. There is certainly a long way to go to perfect these techniques, particularly with regard to biological security and regulation of the element transferred. However, when it is used it will mean a major qualitative change in the treatment of nervous system disorders which are at present a cause of severe handicap and have little chance of treatment.     

Morphological correlates of neural regeneration in the feeding system of Aplysia californica after central nervous system lesions

Specific direct bradykinin (BK) binding and competitive inhibition was detected in human neutrophil and peripheral blood mononuclear cell (PBMC) detergent solubilized extracts and purified plasma membranes using in vitro radioreceptor ligand binding. Scatchard analyses of [125I]-BK binding revealed an equilibrium dissociation constant (Kd) of 2.9 x 10(-11) M for neutrophils and 5.6 x 10(-11) M for PBMC using [des-arg9]-BK a B1 agonist; 2.6 x 10(-11) M for neutrophils, 6.2 x 10(-11) M for PBMC with BK a B2 agonist; 5.4 x 10(-11) M for PBMC using Lys-BK a B2 agonist. The number of binding sites (Bmax) was calculated to be 0.113 fM/microgram protein (720 receptors per cell) for neutrophils and 0.200 fM/microgram protein (1289 receptors per cell) for PBMC with the B1 agonist while with the B2 agonists the values were 0.128 fM/microgram protein (818 receptors per cell) for neutrophils and 0.157 fM/microgram protein (1005 receptors per cell) for PBMC with BK, and 0.293 fM/microgram protein (1870 receptors per cell) with Lys-BK for PBMC. In a competitive binding inhibition assay using neutrophil and PBMC glycerol purified plasma membranes, high affinity binding in the nanomolar range was detected to Lys-BK and BK but with [des-arg9]-BK a 10-100 fold lower order affinity was observed this being indicative of pharmacologically defined B2 characteristics.     

Intracranial metyrapone stimulates CRF-ACTH axis in the teleost, Clarias batrachus: possible role of neurosteroids

Intracranial administration of metyrapone, a blocker of the enzyme 11-beta-hydroxylase, which is essential for the biosynthesis of corticosteroids, resulted in profound stimulation of the nucleus preopticus and the CRF-ACTH axis in the teleost, Clarias batrachus. It is suggested that the putative blockade of the neurosteroid biosynthesis following metyrapone might be responsible for this action. The present study for the first time uncovers the possibility of inhibitory regulation of the CRF-ACTH axis by metyrapone sensitive neurosteroids.     

Experimental strategies to promote axonal regeneration after traumatic central nervous system injury

A damage or pathological process that destroys the continuity of axons in the mature central nervous system (CNS) has devastating consequences and produces lasting functional deficits. One of the major challenges in this field is to stimulate the regrowth of severed axons and reconstruction of pathways. Recent progress in molecular and cell biology has resulted in an explosion of knowledge on factors in the adult CNS being nonsupportive or even actively inhibitory to axonal regrowth. The new findings have a strong impact on the development of new therapeutic concepts directed to stimulate axonal regeneration. They give rise to cautious optimism, showing that under some circumstances repair of a CNS lesion is possible. In this review the authors summarize the current knowledge on the factors and mechanisms involved in regeneration failure and provide an overview of the current therapeutic approaches that may enable effective CNS regeneration in the future.     

What is the role of the sympathetic nervous system in digital vasospasms?

The sympathetic activity is modulated by the cerebral cortex, hypothalamus, medullary vasomotor centers, and spinal cord. Finger blood flow is mainly under the control of the sympathetic nervous system. In digital vasospasm, an increased activity of the sympathetic nervous system is opposed to a local abnormality in the digital arteries. This controversy is discussed with respect to general and local control mechanisms in the peripheral blood circulation.     

A functional role for neutralizing antibodies in Borna disease: influence on virus tropism outside the central nervous system

Borna disease virus (BDV) is a negative-strand RNA virus that infects the central nervous systems (CNS) of warm-blooded animals and causes disturbances of movement and behavior. The basis for neurotropism remains poorly understood; however, the observation that the distribution of infectious virus in immunocompetent rats is different from that in immunoincompetent rats indicates a role for the immune system in BDV tropism: whereas in immunocompetent rats virus is restricted to the central, peripheral, and autonomic nervous systems, immunoincompetent rats also have virus in nonneural tissues. In an effort to examine the influence of the humoral immune response on BDV pathogenesis, we examined the effects of passive immunization with neutralizing antiserum in immunoincompetent rats. Serum transfer into immunoincompetent rats did not prevent persistent CNS infection but did result in restriction of virus to neural tissues. These results indicate that neutralizing antibodies may play a role in preventing generalized infection with BDV.     

Cocaine and the nervous system

Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed.     

The role of the extracellular matrix in neoplastic glial invasion of the nervous system

Intrinsic tumours of the central nervous system (CNS) are generally derived from the glial cells: the astrocytes, oligodendrocytes and ependymal cells. Although such tumours rarely metastasize to distant organs, they show a marked propensity for local invasion of the surrounding nervous tissue. Sub-populations of neoplastic glia may migrate several millimetres away from main tumour mass into the contiguous CNS parenchyma, resulting in poor demarcation of the tumour. These migratory, so-called "guerrilla" cells give rise to recurrent tumours following surgical debulking and adjuvant radio- and chemo-therapeutic intervention. As in other organs, tumour cell invasion is, in part, facilitated by interaction with the extracellular matrix (ECM); however, apart from the vascular basal lamina and the glia limitans externa, the CNS lacks a well-defined ECM. Invading neoplastic cells must, therefore, provide their own ECM, a process which may be stimulated by such agents as gangliosides or growth factors. Glioma cell-derived laminin and hyaluronic acid may provide the most important substrates for invasion, cell adhesion to these substrates being achieved largely through integrin receptors (the function of which may be determined by interaction with cell surface gangliosides) and CD44, respectively. Modulation of these ECM components is facilitated by a variety of proteinases including the matrix metalloproteinases and hyaluronidase, the activity of which is also thought to stimulate angiogenesis. Interference with the mechanisms which promote glioma cell adhesive properties may provide suitable targets for novel anti-invasive therapies. These might include ECM components, growth factors, gangliosides, integrin receptors and proteases and their inhibitors.     

Possible role of the autonomic nervous system in sphincter impairment after restorative proctocolectomy

Peroperative manometry was performed in 12 patients operated on with endoanal proctectomy and a hand-sewn pouch-anal anastomosis and in 12 in whom proctectomy was performed entirely from above, with the ileal pouch stapled to the top of the anal canal. Results from both groups showed that division of the superior rectal artery reduced the median (95 per cent confidence interval (c.i.)) resting anal pressure from 77.5 (69.9-83.3) mmHg to 64.5 (55.2-70.0) mmHg (P < 0.01). Complete rectal mobilization to the pelvic floor decreased resting pressure by an additional 22 per cent, to a median of 50.0 (95 per cent c.i. 40.1-53.5) mmHg (P < 0.01). After completion of anastomosis, irrespective of the operative technique used, a further decline in median pressure to 35.0 (95 per cent c.i. 26.0-47.7) mmHg could be demonstrated (P < 0.05). This study indicates that anal sphincter pressure is reduced to a similar extent after hand-sewn and stapled anastomoses. Injury to the autonomic nervous supply to the anal sphincter mechanism might be the major cause for this reduction.     

Optic neuromyelitis: a necrotizing disease of the central nervous system]

Optic neuromyelitis is characterized by simultaneous or successive necrotizing lesions involving the optic nerves and the spinal cord. We report two females with the disease, aged 30 and 34 years old. In the latter, a neuropathological study was done. Both patients had clinical, neuroradiological and pathological features that differed from those of primary demyelinating syndromes such as multiple sclerosis. These patients illustrate the selectivity of optic nerve and spinal cord lesions. The latter involve mainly pyramidal and Goll tracts while, within the necrotizing lesions of the optic chiasma, the fibers of the unaffected optic nerve are spared. This pattern suggests a selective injury to some population of axons. Blood vessels were not affected in the necrotizing areas and the lesions did not follow a vascular territory, therefore a vascular mechanism causing the disease is unlikely. The clinical and neuropathological features of neuromyelitis optic suggest a selective involvement of some axons.     

Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system

NIMA protein kinase is a major regulator of progression into mitosis in Aspergillus nidulans. Dominant negative forms of NIMA protein prevent entrance into mitosis in HeLa cells, suggesting that mammals have a similar pathway. We have reported previously the isolation of a murine NIMA-related kinase, designated Nek1, and more recently several additional NIMA-related human kinases have been cloned. The existence of several mammalian NIMA-related genes raises the questions of whether the different mammalian members have redundant, overlapping or distinct functions, and whether these functions are related to the role of NIMA in controlling mitosis. To address these questions we have studied the expression patterns of the different murine nek genes. To this end, we isolated a murine nek2 cDNA and compared its patterns of expression, during both gametogenesis and embryogenesis, to those of nek1. Both genes were highly expressed in developing germ cells, albeit in distinct patterns. In both females and males, nek1 is expressed much earlier than nek2, suggesting only limited ability for functional redundancy. Surprisingly, a striking specificity of nek1 expression was found: high levels of nek1 RNA were observed in distinct regions of the nervous system, most notably in neurons of the peripheral ganglia. These patterns suggest that the different mammalian NIMA-related kinases participate in different phases of the meiotic process and may also have functions other than cell cycle control.