Computed tomography provides enhanced techniques for longitudinal monitoring of progressive intracranial volume loss associated with regional neurodegeneration in ovine neuronal ceroid lipofuscinoses.

Autor: Russell KN; Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand., Mitchell NL; Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand.; Department of Radiology, University of Otago, Christchurch, New Zealand., Anderson NG; Department of Radiology, University of Otago, Christchurch, New Zealand., Bunt CR; Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand., Wellby MP; Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand., Melzer TR; Department of Medicine, University of Otago, Christchurch, New Zealand.; New Zealand Brain Research Institute, Christchurch, New Zealand., Barrell GK; Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand., Palmer DN; Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, New Zealand.; Department of Radiology, University of Otago, Christchurch, New Zealand.
Jazyk: angličtina
Zdroj: Brain and behavior [Brain Behav] 2018 Sep; Vol. 8 (9), pp. e01096. Date of Electronic Publication: 2018 Aug 23.
DOI: 10.1002/brb3.1096
Abstrakt: Introduction: The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of fatal neurodegenerative lysosomal storage diseases of children caused by various mutations in a range of genes. Forms associated with mutations in two of these, CLN5 and CLN6, are being investigated in well-established sheep models. Brain atrophy leading to psychomotor degeneration is among the defining features, as is regional progressive ossification of the inner cranium. Ongoing viral-mediated gene therapy trials in these sheep are yielding encouraging results. In vivo assessment of brain atrophy is integral to the longitudinal monitoring of individual animals and provides robust data for translation to treatments for humans.
Methods: Computed tomography (CT)-based three-dimensional reconstruction of the intracranial volume (ICV) over time reflects the progression of cortical brain atrophy, verifying the use of ICV measurements as a surrogate measure for brain size in ovine NCL.
Results: ICVs of NCL-affected sheep increase for the first few months, but then decline progressively between 5 and 13 months in CLN5 -/- sheep and 11-15 months in CLN6 -/- sheep. Cerebral ventricular volumes are also increased in affected animals. To facilitate ICV measures, the radiodensities of ovine brain tissue and cerebrospinal fluid were identified. Ovine brain tissue exhibited a Hounsfield unit (HU) range of (24; 56) and cerebrospinal fluid a HU range of (-12; 23).
Conclusions: Computed tomography scanning and reconstruction verify that brain atrophy ovine CLN5 NCL originates in the occipital lobes with subsequent propagation throughout the whole cortex and these regional differences are reflected in the ICV loss.
(© 2018 Lincoln University. Brain and Behavior published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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