Specific neuro-radiological diagnosis of Herpes encephalitis in an animal model

Cleator, Graham M.; Klapper, Paul E.; Lewis, Alfor G.; Hl, Sharma; Longson, Maurice

doi:10.1007/bf01314647

Cited by 13 publications

(3 citation statements)

References 17 publications

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“…S4A; see also Ishii & Iadecola, 2015). Some microbes may target the hypothalamus directly: a restricted but intense focus of virus replication was observed in rat hypothalamus following inoculation of herpes simplex virus (HSV-1) (Cleator et al, 1988) (Fig. S4B).…”

Section: Ageing Immunosenescence and Age-related Diseasementioning

confidence: 99%

Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease

Lathe

Clair

2023

Biological Reviews

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The characteristic maximum lifespan varies enormously across animal species from a few hours to hundreds of years. This argues that maximum lifespan, and the ageing process that itself dictates lifespan, are to a large extent genetically determined. Although controversial, this is supported by firm evidence that semelparous species display evolutionarily programmed ageing in response to reproductive and environmental cues. Parabiosis experiments reveal that ageing is orchestrated systemically through the circulation, accompanied by programmed changes in hormone levels across a lifetime. This implies that, like the circadian and circannual clocks, there is a master ‘clock of age’ (circavital clock) located in the limbic brain of mammals that modulates systemic changes in growth factor and hormone secretion over the lifespan, as well as systemic alterations in gene expression as revealed by genomic methylation analysis. Studies on accelerated ageing in mice, as well as human longevity genes, converge on evolutionarily conserved fibroblast growth factors (FGFs) and their receptors, including KLOTHO, as well as insulin‐like growth factors (IGFs) and steroid hormones, as key players mediating the systemic effects of ageing. Age‐related changes in these and multiple other factors are inferred to cause a progressive decline in tissue maintenance through failure of stem cell replenishment. This most severely affects the immune system, which requires constant renewal from bone marrow stem cells. Age‐related immune decline increases risk of infection whereas lifespan can be extended in germfree animals. This and other evidence suggests that infection is the major cause of death in higher organisms. Immune decline is also associated with age‐related diseases. Taking the example of Alzheimer's disease (AD), we assess the evidence that AD is caused by immunosenescence and infection. The signature protein of AD brain, Aβ, is now known to be an antimicrobial peptide, and Aβ deposits in AD brain may be a response to infection rather than a cause of disease. Because some cognitively normal elderly individuals show extensive neuropathology, we argue that the location of the pathology is crucial – specifically, lesions to limbic brain are likely to accentuate immunosenescence, and could thus underlie a vicious cycle of accelerated immune decline and microbial proliferation that culminates in AD. This general model may extend to other age‐related diseases, and we propose a general paradigm of organismal senescence in which declining stem cell proliferation leads to programmed immunosenescence and mortality.

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Section: Ageing Immunosenescence and Age-related Diseasementioning

confidence: 99%

Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease

Lathe

Clair

2023

Biological Reviews

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“…Beginning in the early 1980s, investigators succeeded in showing that, even though the blood-brain barrier normally restricts the entry of deoxythymidine analogues into the central nervous system, the increased permeability associated with viral infection permitted the entry of a sufficient amount of probe to label infected cells. In a series of studies, rats were infected intraocularly with HSV-1, and after an appropriate interval were injected intravenously with a small dose of 14 C-labeled 2 -fluoro-5methyl-1-␤-d-arabinosyluracil (FMAU) or with 131 I-or 125 I-labeled E-5-(2-iodovinyl)-2 -deoxyuridine (IVDU) (Gill et al, 1984;Klapper et al, 1988;Price et al, 1983;Saito et al, 1984;Cleator et al, 1988). Foci of encephalitis were identified either by killing animals and performing autoradiography on brain slices, or by imaging live animals using a gamma camera.…”

Section: Virus-specific Radionuclide Imaging: the Herpesviral Tk As Amentioning

confidence: 99%

Radiolabeled antiviral drugs and antibodies as virus-specific imaging probes

et al. 2010

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A number of small-molecule drugs inhibit viral replication by binding directly to virion structural proteins or to the active site of a viral enzyme, or are chemically modified by a viral enzyme before inhibiting a downstream process. Similarly, antibodies used to prevent or treat viral infections attach to epitopes on virions or on viral proteins expressed on the surface of infected cells. Such drugs and antibodies can therefore be thought of as probes for the detection of viral infections, suggesting that they might be used as radiolabeled tracers to visualize sites of viral replication by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. A current example of this approach is the PET imaging of herpes simplex virus infections, in which the viral thymidine kinase phosphorylates radiolabeled thymidine analogues, trapping them within infected cells. One of many possible future applications might be the use of a radiolabeled hepatitis C protease inhibitor to image infection in animals or humans and provide a quantitative measure of viral burden. This article reviews the basic features of radionuclide imaging and the characteristics of ideal tracer molecules, and discusses how antiviral drugs and antibodies could be evaluated for their suitability as virus-specific imaging probes. The use of labeled drugs as low-dose tracers would provide an alternative application for compounds that have failed to advance to clinical use because of insufficient in vivo potency, an unsuitable pharmacokinetic profile or hepato- or nephrotoxicity.

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“…On development of signs of encephalitis (4 to 6 days post-infection), animals were anaesthetised and a polyethylene cannula was secured in the left common carotid artery as described previously [2]. Infected or non-infected animals were placed on a heated table with the head positioned 4 cm beneath the pin-hole collimator of a Nuclear-Chicago gamma camera (Nuclear Enterprises, Edinburgh) such that only brain-associated radioactivity was monitored.…”

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confidence: 99%