Abstract:
:Cell death in gliomas may occur either by apoptosis, or, in the case of high grade tumours, by necrosis, but questions remain as to the pathogenesis and relationship between these processes. The development of cell death was investigated in multicellular glioma spheroid cultures. Spheroids model the development of cell death due to diffusion gradients in a three-dimensional system without confounding influences of immune response, pressure gradients, etc. Spheroid cultures were established from four malignant glioma cell lines: U87, U373, MOG-G-CCM and A172; harvested from culture at weekly intervals and stained with Haematoxylin and Eosin (H&E), TdT-mediated dUTP-X nick end labelling (TUNEL) and by immunohistochemistry for vimentin, Glial Fibrillary Acidic Protein (GFAP) and Ki67. Annexin V flow cytometry and counts of apoptotic cells on H & E stained sections were performed to assess levels of apoptosis. Modes of cell death were also characterized by electron microscopy. Spatially separate zones of proliferation, differentiation and central cell death developed with increasing spheroid diameter. Central cell death developed at a predictable radius (300-400 microm) for each cell line. Ultrastructural examination showed this to be necrotic in type. Apoptosis was most reliably assayed by morphological counts using H & E. Basal levels of apoptosis were low (< 0.5%), but increased with increasing spheroid diameter (> 2% in U87). In particular, levels of apoptosis rose following development of central necrosis and apoptoses were most abundant in the peri-necrotic zone. There were quantitative differences in the levels of apoptosis and necrosis between glioma cell lines. The predictable onset of necrosis in the spheroids will allow us to investigate the pathogenesis of necrosis and events in prenecrotic cells. There is a relationship between the development of necrosis and apoptosis in this model and these processes can be separately assayed. Further in vitro and genetic studies will enable us to study these events and interactions in greater detail than is possible using other cell culture and in vivo systems.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Bell HS,Whittle IR,Walker M,Leaver HA,Wharton SBdoi
10.1046/j.0305-1846.2001.00319.xkeywords:
subject
Has Abstractpub_date
2001-08-01 00:00:00pages
291-304issue
4eissn
0305-1846issn
1365-2990pii
nan319journal_volume
27pub_type
杂志文章abstract::Dementia with Lewy bodies (DLB) is characterized by the widespread presence of Lewy bodies (LBs) in the brain. alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. We compared alpha-synuclein 112 and alpha-syn...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00572.x
更新日期:2004-12-01 00:00:00
abstract:INTRODUCTION:Cerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood. In Alzheimer's disease (AD), there is early loss of synaptic proteins, but these have been little studied in VAD. MATERIALS AND METHOD...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12215
更新日期:2015-06-01 00:00:00
abstract:AIMS:Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology. METHODS:Fr...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12252
更新日期:2016-02-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascula...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2004.00600.x
更新日期:2004-10-01 00:00:00
abstract::In this study we describe the effects of trapidil, a putative platelet-derived growth factor-antagonist, on spontaneously occurring remyelination in rat spinal cord. Demyelination was created in the dorsal funiculus of 6- and 11-week-old female rats by the direct injection of 1.0 microliter of 1% lysolecithin. The ani...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::The molecular genetic analysis of brain tumours has been the focus of considerable interest for a number of years. However, these studies have been largely directed towards understanding the fundamental biological processes involved in tumorigenesis and the techniques which have been used require considerable molecula...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.1997.tb01321.x
更新日期:1997-12-01 00:00:00
abstract::A single dose (19 mg kg-1) of triethyllead given to weanling rats produces necrosis in a small number of hippocampal pyramidal (CA3) and hilar neurons with reversible changes in the remaining neurons of this region. The sequence of events has been studied by light and electron microscopy over a period from 12 h to 14 ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1989.tb01245.x
更新日期:1989-09-01 00:00:00
abstract::Changes of 5'-nucleotidase (5'-N) activity during subcultivation of C6 clonal rat glioma cells were studied histochemically, cytochemically and biochemically. Two different cell populations were seeded with high or low cell density respectively. 5'-N activity in cultured cells increased continuously in both population...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00014.x
更新日期:1985-05-01 00:00:00
abstract:AIMS:EphB2 is a member of receptor tyrosine kinases (RTKs) family that is essential for the cell adhesion, neural crest migration, axon guidance and synaptogenesis in the nervous system. Recent studies show that preservation of EphB2 in a transgenic mouse model of Alzheimer's disease (AD) rescues the cognitive deficit,...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12019
更新日期:2013-10-01 00:00:00
abstract::Pathologists have been establishing archives of human organs and tissue for research use for many years now. Controversy has arisen recently over these collections, particularly with regard to the right of patients or relatives to consent to removal and retention of tissue, genetic research using stored tissue samples...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2990.2000.00276.x
更新日期:2000-10-01 00:00:00
abstract::Chicks were fed a diet rich in oxidized oil and deficient in alpha-tocopherol. As soon as nutritional encephalopathy developed the animals were immediately put on to a normal diet, and kept alive for up to 166 days. Examination of the cerebellum showed multiple foci of healed encephalomalacia with EM appearance of bas...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1980.tb00198.x
更新日期:1980-01-01 00:00:00
abstract:AIMS:Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12428
更新日期:2018-02-01 00:00:00
abstract::The human chromosome 22 displays an unusual concentration of medically relevant genes, especially gene(s) involved in malignancies of the central nervous system. A full genomic and transcriptional characterization of this autosome will no doubt make a strong impact on the understanding of some of the processes which l...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.1996.tb00912.x
更新日期:1996-10-01 00:00:00
abstract:AIMS:Much evidence demonstrates that Toll-like receptor-4 (TLR4)-mediated microglial activation is an important contributor to the inflammatory injury in intracerebral haemorrhage (ICH). However, the exact mechanism of TLR4-mediated microglial activation induced by ICH is not clear. In addition, microglial autophagy is...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12177
更新日期:2015-06-01 00:00:00
abstract::The development of granule cells and the formation of synapses with mossy fibres were investigated in cerebella from jaundiced (j/j) Gunn rats with hereditary hyperbilirubinemia. The external granular layer was thinner than that in cerebella from heterozygous (+/j) Gunn rats without hyperbilirubinemia on days 12 and 1...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1993.tb00445.x
更新日期:1993-08-01 00:00:00
abstract::Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01036.x
更新日期:1995-04-01 00:00:00
abstract::To confirm the intracellular accumulation of amyloid beta-protein (Abeta), we carefully performed immunohistochemistry using brains of cynomolgus monkeys of various ages. Cortical neurones and their large neurites were immunostained with antibodies against Abeta in young monkey brains. In aged monkey brains, intracell...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00624.x
更新日期:2005-04-01 00:00:00
abstract::Paediatric diffuse high-grade gliomas (pHGG) are rare, but deadly tumours. The discovery of recurrent mutations in the tail of histone H3, changing lysine 27 to methionine, or glycine 34 to arginine or valine, has illuminated a critical role for epigenetic dysregulation in the aetiology of childhood gliomas and opened...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12591
更新日期:2020-02-01 00:00:00
abstract::The pathological findings in Alzheimer's disease (AD) are partly attributed to alterations in calcium-binding protein (CBP) functions. We showed previously that immunoreactivity of secretagogin, a recently cloned CBP, in the human hippocampus is restricted to pyramidal neurones and that the amount of immunoreactive ne...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2007.00854.x
更新日期:2008-02-01 00:00:00
abstract::Damage to the frontal cortex and to the hippocampus, both in terms of cell loss and neuronal dysfunction, is thought to underlie many of the neurological and behavioural consequences of traumatic brain injury (TBI). Several studies have indicated that the hippocampus is particularly susceptible to central nervous syst...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2003.00439.x
更新日期:2003-04-01 00:00:00
abstract:AIMS:Frontotemporal lobar degeneration (FTLD) and motor neurone disease are linked by the possession of a hexanucleotide repeat expansion in C9ORF72, and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are TDP-43 negative but immunoreactive for p62 and dipeptide repeat protein...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12178
更新日期:2015-08-01 00:00:00
abstract::Minute amounts of tetanus toxin injected into the hippocampus of rats results in an epileptiform syndrome. When the toxin injection is made unilaterally or bilaterally into the ventral hippocampus, about one-third of animals with seizures show bilateral neuronal loss in dorsal CA1 of the hippocampus after 1 week. In a...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1994.tb00985.x
更新日期:1994-08-01 00:00:00
abstract::In many experimental models of skeletal muscle damage and in human muscle disease, empty basement membrane tubes remain following the destruction of muscle fibres. In the present study we test the hypothesis that the empty basement membrane tubes play an essential role in the orientation of regenerating muscle fibres....
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1990.tb01159.x
更新日期:1990-06-01 00:00:00
abstract:AIMS:The aim of this study was to describe the regional profiles of microglial activation in sporadic Creutzfeldt-Jakob disease (sCJD) subtypes and analyse the influence of prion strain, disease duration and codon 129 genotype. METHODS:We studied the amount/severity and distribution of activated microglia, protease-re...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12461
更新日期:2018-10-01 00:00:00
abstract::Tubular vesicular and net-like dissolution of myelin sheaths associated with complete demyelination and preservation of axons, is described in the brain, obtained within 4 h of death, from a patient who died with acute multiple sclerosis (MS). It was rare, being found in only three out of twenty-three blocks examined,...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1979.tb00627.x
更新日期:1979-08-01 00:00:00
abstract:AIMS:Wnt activation in medulloblastomas is associated with good outcome. Upfront testing and risk-adapted stratification of patients will be done in future clinical studies. In a cohort of 186 paediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup. ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12161
更新日期:2015-02-01 00:00:00
abstract::Human fetal dorsal root ganglia aged from 8 to 12 weeks post-menstrual were grown in vitro for up to 20 days. Outgrowth of Schwann cells, axons and fibroblasts occurred after 4 h. By the 7th day in vitro Schwann cells enclosed bundles of axons and after 10 days some Schwann cells were seen to enclose individual axons....
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1982.tb00315.x
更新日期:1982-11-01 00:00:00
abstract::There is a great deal of evidence suggesting an important role for systemic inflammation in the pathogenesis of Alzheimer's disease. The role of systemic inflammation, and indeed inflammation in general, is still largely considered to be as a contributor to the disease process rather than of aetiological importance al...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2012.01307.x
更新日期:2013-02-01 00:00:00
abstract::The aims of this experimental scanning electron microscopic study were to identify the levels at which cervical ventral nerve roots, or the rootlets by which they are attached to the spinal cord, rupture under traction and to document the resulting damage. This information would provide the basis of a rationale for re...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1989.tb01254.x
更新日期:1989-11-01 00:00:00
abstract::Rats were given 2,5-hexanediol in their water for more than 5 weeks. The changes in the optic pathways were studied both qualitatively and quantitatively. Increase in 10-nm filaments within axons was noticeable from 10 days onwards in the superior colliculus and in the brachium of the superior colliculus. From then on...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1982.tb00298.x
更新日期:1982-07-01 00:00:00