1,721,522 research outputs found
Perry V. Whitmore Korean War collection [DIGITAL CONTENT]
No full textThis collection contains an oral history interview with Perry V. Whitmore from December 2, 2008, as well as memoir of his military service
Innate inflammation in Parkinson's disease
No full textThe resident macrophages of the brain-the microglia-are morphologically activated during the progression of Parkinson's disease. Observational studies in human postmortem material and studies in animal models seek to define the contribution that this innate immune response might make to the pathogenesis and rate of progression of Parkinson's disease. We review here some of the key conceptual issues that need to be considered when performing these studies. We highlight the fact that most postmortem studies have not given due consideration to common comorbidities present in patients with Parkinson's disease and also the limitations of attempting to extrapolate from animal models to a chronic progressive neurodegenerative disease in humans that lasts for many years.</p
Persistent pathogens in the parenchyma of the brain
No full textIt has recently been shown that bacteria and viruses can be delivered to the brain parenchyma without evoking an immune response. These experiments demonstrate that there are no cells within the brain parenchyma that can initiate a primary immune response, and that the drainage of pathogens from the brain parenchyma is distinct from that documented for soluble proteins. A persistent pathogen in the brain parenchyma can become a target for the immune system following peripheral sensitisation, and this may lead to bystander tissue damage. These observations may have consequences for vaccination of persons with central nervous system HIV infection
A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation
No full textThere are numerous observations reporting that phagocytes expressing major histocompatibility complex (MHC) Class II molecules are associated with the central nervous system (CNS) in normal and pathological conditions. Although MHC Class II expression is necessary for antigen presentation to CD4 + T-cells, it is not sufficient and co-stimulatory molecules are also required. We review here recent in vivo studies demonstrating that the microglia and perivascular macrophages are unable to initiate a primary immune response in the CNS microenvironment, but may support secondary immune responses. Although in vitro studies show that microgila do not support a primary immune response leading to T-cell proliferation, they do show that microglia may protect the CNS from the unwanted attentions of autoreactive T- cells by inducing their apoptosis. The lack of cells in the CNS parenchyma with the ability to initiate a primary immune response has a cost, namely that pathogens may persist in the CNS undetected by the immune system.</p
Microglial priming in neurodegenerative disease
No full textUnder physiological conditions, the number and function of microglia-the resident macrophages of the CNS-is tightly controlled by the local microenvironment. In response to neurodegeneration and the accumulation of abnormally folded proteins, however, microglia multiply and adopt an activated state-a process referred to as priming. Studies using preclinical animal models have shown that priming of microglia is driven by changes in their microenvironment and the release of molecules that drive their proliferation. Priming makes the microglia susceptible to a secondary inflammatory stimulus, which can then trigger an exaggerated inflammatory response. The secondary stimulus can arise within the CNS, but in elderly individuals, the secondary stimulus most commonly arises from a systemic disease with an inflammatory component. The concept of microglial priming, and the subsequent exaggerated response of these cells to secondary systemic inflammation, opens the way to treat neurodegenerative diseases by targeting systemic disease or interrupting the signalling pathways that mediate the CNS response to systemic inflammation. Both lifestyle changes and pharmacological therapies could, therefore, provide efficient means to slow down or halt neurodegeneration<br/
Cat and monkey retinal ganglion cells and their visual functional roles
No full textRetinal ganglion cells, the integrative-output neurons of the retina, can be sorted into functional classes. In the cat, two ganglion cell classes are labelled X and Y. These are distinguished by the different retinal subnetworks that provide their input. X cells are driven by a single linear receptive field center mechanism. Y cells receive center and surround signals and additional signals from nonlinear subunits in their receptive fields. Both X and Y cells are highly sensitive to contrast. X cells project almost exclusively to the A or A1 layers of the lateral geniculate nucleus (LGN). Y cell axons terminate in the A or A1 layers and also the more ventral C layers, and also the superior colliculus. In the monkey, P cells connect the retina to the parvocellular layers of the LGN, have small receptive fields, are wavelength-selective, and are insensitive to contrast. M cells are ganglion cells that send axons to the magnocellular layers of the LGN, are not wavelength-selective, have somewhat larger receptive fields than P cells, and are very sensitive to contrast. Comparisons between cat and monkey ganglion cell classes reveal several important similarities between M cells and X cells.</p
Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases
No full textWe have studied the effect of an inhibitor of matrix metalloproteinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guerin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCC (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-α release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animaIs. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but o a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-α production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.</p
Dendritic competition: competition for what?
No full textA lesion to the retina of a newborn rat results in the retrograde degeneration of ganglion cells in a sector of retina peripheral to the lesion. The dendritic tree of ganglion cells bordering the region depleted of ganglion cells have their dendrites preferentially directed into this area. We have examined the factors which play a role in this rearrangement of the dendritic tree. The results show that the lesion in neonates selects for or produces a population of cells with the axon directed away from the depleted area and primary dendrites directed towards the depleted area. The abnormal dendritic bias cannot be accounted for solely on the basis of a decrease in contact inhibition since a reduction in the density of all ganglion cells by 30% prior to making the retinal lesion does not attenuate the abnormal dendritic bias into the depleted area. The abnormal dendritic bias is present in animals operated on up to 15 days of age postnatally but not in more mature animals. The abnormal dendritic bias develops prior to the formation of a large number of synapses in the inner nuclear layer. Our results cannot be easily accounted for by competition for synaptic contacts or a loss of contact inhibition as previously suggested. We propose that chemotropic factors produced within the area depleted of ganglion cells induce the abnormal dendritic bias and the number of synaptic contacts may limit the size of the dendritic field.</p
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