An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.     

Private long-term care insurance. Simulations of a potential market

Long-term care is now the most common cause of catastrophic illness costs for the elderly. Although acute care health insurance represents a mature market, private long-term care insurance is in its infancy and poised for development. This study presents a comparative analysis of simulation data, generated from the Brookings-ICF Long-Term Care Financing Model, for five alternative private long-term care insurance models. The simulation results indicate 1) the potential market for private long-term care insurance is substantial, 2) moderately comprehensive long-term care policies are affordable by a significant minority of the elderly, 3) policies are considerably more affordable to those under age 65, and 4) long-term care insurance has somewhat less potential to pay for nursing home costs for high risk groups than for other elderly.     

Projections of the bed nucleus of the stria terminalis to the mesencephalon,pons, and medulla oblongata in the cat

Summary Injections of HRP in the nucleus raphe magnus and adjoining medial reticular formation in the cat resulted in many labeled neurons in the lateral part of the bed nucleus of the stria terminalis (BNST) but not in the medial part of this nucleus. HRP injections in the nucleus raphe pallidus and in the C2 segment of the spinal cord did not result in labeled neurons in the BNST. Injections of ³H-leucine in the BNST resulted in many labeled fibers in the brain stem. Labeled fiber bundles descended by way of the medial forebrain bundle and the central tegmental field to the lateral tegmental field of pons and medulla. Dense BNST projections could be observed to the substantia nigra pars compacta, the ventral tegmental area, the nucleus of the posterior commissure, the PAG (except its dorsolateral part), the cuneiform nucleus, the nucleus raphe dorsalis, the locus coeruleus, the nucleus subcoeruleus, the medial and lateral parabrachial nuclei, the lateral tegmental field of caudal pons and medulla and the nucleus raphe magnus and adjoining medial reticular formation. Furthermore many labeled fibers were present in the solitary nucleus, and in especially the peripheral parts of the dorsal vagal nucleus. Finally some fibers could be traced in the marginal layer of the rostral part of the caudal spinal trigeminal nucleus. These projections appear to be virtually identical to the ones derived from the medial part of the central nucleus of the amygdala (Hopkins and Holstege 1978). The possibility that the BNST and the medial and central amygdaloid nuclei must be considered as one anatomical entity is discussed.Abbreviations AA anterior amygdaloid nucleus - AC anterior commissure - ACN nucleus of the anterior commissure - ACO cortical amygdaloid nucleus - AL lateral amygdaloid nucleus - AM medial amygdaloid nucleus - APN anterior paraventricular thalamic nucleus - AQ cerebral aqueduct - BC brachium conjunctivum - BIC brachium of the inferior colliculus - BL basolateral amygdaloid nucleus - BNSTL lateral part of the bed nucleus of the stria terminalis - BNSTM medial part of the bed nucleus of the stria terminalis - BP brachium pontis - CA central nucleus of the amygdala - Cd caudate nucleus - CI inferior colliculus - CL claustrum - CN cochlear nucleus - CP posterior commissure - CR corpus restiforme - CSN superior central nucleus - CTF central tegmental field - CU cuneate nucleus - D nucleus of Darkschewitsch - EC external cuneate nucleus - F fornix - G gracile nucleus - GP globus pallidus - HL lateral habenular nucleus - IC interstitial nucleus of Cajal - ICA internal capsule - IO inferior olive - IP interpeduncular nucleus - LC locus coeruleus - LGN lateral geniculate nucleus - LP lateral posterior complex - LRN lateral reticular nucleus - MGN medial geniculate nucleus - MLF medial longitudinal fascicle - NAdg dorsal group of nucleus ambiguus - NPC nucleus of the posterior commissure - nV trigeminal nerve - nVII facial nerve - OC optic chiasm - OR optic radiation - OT optic tract - P pyramidal tract - PAG periaqueductal grey - PC cerebral peduncle - PO posterior complex of the thalamus - POA preoptic area - prV principal trigeminal nucleus - PTA pretectal area - Pu putamen - PUL pulvinar nucleus - R red nucleus - RF reticular formation - RM nucleus raphe magnus - RP nucleus raphe pallidus - RST rubrospinal tract - S solitary nucleus - SC suprachiasmatic nucleus - SCN nucleus subcoeruleus - SI substantia innominata - SM stria medullaris - SN substantia nigra - SO superior olive - SOL solitary nucleus - SON supraoptic nucleus - spV spinal trigeminal nucleus - spVcd spinal trigeminal nucleus pars caudalis - ST stria terminalis - TRF retroflex tract - VC vestibular complex - VTA ventral tegmental area of Tsai - III oculomotor nucleus - Vm motor trigeminal nucleus - VI abducens nucleus - VII facial nucleus - Xd dorsal vagal nucleus - XII hypoglossal nucleus     

A synthetic nanofibrillar matrix promotes in vivo-like organization and morphogenesis for cells in culture

The purpose of this study was to design a synthetic nanofibrillar matrix that more accurately models the porosity and fibrillar geometry of cell attachment surfaces in tissues. The synthetic nanofibrillar matrices are composed of nanofibers prepared by electrospinning a polymer solution of polyamide onto glass coverslips. Scanning electron and atomic force microscopy showed that the nanofibers were organized into fibrillar networks reminiscent of the architecture of basement membrane, a structurally compact form of the extracellular matrix (ECM). NIH 3T3 fibroblasts and normal rat kidney (NRK) cells, when grown on nanofibers in the presence of serum, displayed the morphology and characteristics of their counterparts in vivo. Breast epithelial cells underwent morphogenesis to form multicellular spheroids containing lumens. Hence the synthetic nanofibrillar matrix described herein provides a physically and chemically stable three-dimensional surface for ex vivo growth of cells. Nanofiber-based synthetic matrices could have considerable value for applications in tissue engineering, cell-based therapies, and studies of cell/tissue function and pathology.     

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.