title: In vivo morphological changes in animal models of amyotrophic lateral sclerosis and Alzheimer's-like disease: MRI approach.
abstract: Magnetic resonance imaging (MRI) is the only noninvasive technique that provides structural information on both cell loss and metabolic changes. After reviewing all the results obtained in clinical studies, reliable biomarkers in neurological diseases are still lacking. Diffusional MRI, MR spectroscopy, and the assessment of regional atrophy are promising approaches, but they cannot be simultaneously used on a single patient. Thus, for further research progress, reliable animal models are needed. To this aim, we have used the clinical MRI to assess neurodegenerative processes in the hSOD-1(G93A) ALS rat model and in the trimethyltin (TMT)-treated model of Alzheimer's-like disease. T2-weighted (T2W) hyperintensive neurodegenerative foci were found in the brainstem of the ALS rat with apparent lateral ventricle dilation (T1W-hypointensity vs. T2W-hyperintensity). Degenerative processes in these areas were also confirmed by confocal images of GFAP-positive astrogliosis. MRI after i.v.i. of magnetic anti-CD4 antibodies indicated an accumulation of inflammatory cells near dilated ventricles. TMT-treated rats also revealed the dilation of lateral ventricles. Expected deterioration in the hippocampus was not observed by clinical MRI, but immunocytochemistry could reveal significant redistribution of macro- and microglia in this structure. In both models, Gd-DTPA contrast revealed a compromised blood brain barrier that may serve as the passage for inflammatory immune cells in the vicinity of dilated lateral ventricles. Moreover, in both models the midbrain region of the dorsal hippocampus was the target of BBB compromise, thus revealing a potentially vulnerable point that can be the primary target of neurodegeneration in the central nervous system.
authors: Department of Physiology and Biochemistry, School of Biology, University of Belgrade, Studentski trg 12, Belgrade, Serbia. pandjus@bio.bg.ac.rs
authors: Pavle R
authors: PR
authors: Andjus
authors: Danijela
authors: D
authors: Bataveljić
authors: Greetje
authors: G
authors: Vanhoutte
authors: Dinko
authors: D
authors: Mitrecic
authors: Fabrizio
authors: F
authors: Pizzolante
authors: Nevena
authors: N
authors: Djogo
authors: Charles
authors: C
authors: Nicaise
authors: Fabrice
authors: F
authors: Gankam Kengne
authors: Carlo
authors: C
authors: Gangitano
authors: Fabrizio
authors: F
authors: Michetti
authors: Annemie
authors: A
authors: van der Linden
authors: Roland
authors: R
authors: Pochet
authors: Goran
authors: G
authors: Bacić
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats