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

Autor: David N. Palmer, Nigel G. Anderson, Graham K. Barrell, Martin Wellby, Katharina N. Russell, Craig R. Bunt, Nadia L. Mitchell, Tracy R. Melzer
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Batten disease
Pathology
Behavioral Neuroscience
0302 clinical medicine
Cerebrospinal fluid
Cortex (anatomy)
Longitudinal Studies
Hounsfield units
Original Research
longitudinal monitoring
neuroimaging
Neurodegeneration
neurodegeneration
NCL
Organ Size
in vivo
medicine.anatomical_structure
Brain size
Disease Progression
Female
medicine.symptom
neuronal ceroid lipofuscinoses
CT
medicine.medical_specialty
brain
03 medical and health sciences
Atrophy
Neuroimaging
cranial ossification
Neuronal Ceroid-Lipofuscinoses
medicine
Animals
Humans
3D reconstruction
Sheep
Ossification
business.industry
Membrane Proteins
Reproducibility of Results
radio‐density
medicine.disease
Disease Models
Animal
030104 developmental biology
Tomography
X-Ray Computed
business
030217 neurology & neurosurgery
Zdroj: Brain and Behavior
ISSN: 2162-3279
DOI: 10.1002/brb3.1096
Popis: 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.
Databáze: OpenAIRE
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