G. Carpinelli¹, R. Canese¹, V. Vetrugno², M.A. Di Bari³, F. Santoro¹, M. Lu², M. Sbriccoli²,  M. Pocchiari², U. Agrimi³ and F. Podo¹

¹Unit of Molecular and Cellular Imaging, ²Unit of Clinic Diagnostic and Therapy of Degenerative Central Nervous System Diseases, Department of Cell Biology and Neurosciences, ³Unit of Transmissible Spongiform Encephalopathies and Emerging Infectious Diseases of Animals, Department of  Veterinary Public Health and Food Safety; Istituto Superiore di Sanità, I-00161 Rome, Italy.

Abstract

Background and Purpose: Transmissible spongiform encephalopathy (TSE) diseases are fatal, progressive neurodegenerative disorders affecting both humans and animals. Clinical signs typically appear after years and even decades of silent disease progression. This study was aimed at investigating whether altered brain MRI patterns may precede clinical signs in a TSE rodent model.

Methods: In vivo T2-weighted (T2W) MRI examinations (4.7 T) were performed on Golden Syrian hamsters (GSH) intracerebrally, orally, or intraperitoneally (i.p.) infected with the 263K scrapie strain. Histopathological analyses were performed on i.p. infected GSH at the end of one-day or longitudinal MRI sessions.

Results: T2W-MRI hyperintensity was detected in the thalamic nuclei of GSH with clinical signs, irrespective of the infection route. Hyperintensity in the thalamus was also observed in pre-clinical animals, between 106 and 121 days post-infection (dpi), while normal T2W intensity was detected in four animals examined between 72 and 96 dpi. Pathological prion protein deposition (but no astrogliosis and only occasionally, weak spongiosis) was detected between 106 and 121 dpi.

Conclusions: The altered T2W-MRI pattern detected in the thalamus of asymptomatic i.p. infected GSH provides a useful basis for evaluating the effectiveness of possible therapeutic approaches at early stages of TSE disease.