TY - JOUR
T1 - In vivo morphological changes in animal models of amyotrophic lateral sclerosis and Alzheimer's-like disease
T2 - MRI approach
AU - Andjus, Pavle R
AU - Bataveljić, Danijela
AU - Vanhoutte, Greetje
AU - Mitrecic, Dinko
AU - Pizzolante, Fabrizio
AU - Djogo, Nevena
AU - Nicaise, Charles
AU - Gankam Kengne, Fabrice
AU - Gangitano, Carlo
AU - Michetti, Fabrizio
AU - van der Linden, Annemie
AU - Pochet, Roland
AU - Bacić, Goran
N1 - (c) 2009 Wiley-Liss, Inc.
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Alzheimer Disease
KW - Amyotrophic Lateral Sclerosis
KW - Animals
KW - Blood-Brain Barrier
KW - Brain
KW - Chemotaxis, Leukocyte
KW - Disease Models, Animal
KW - Encephalitis
KW - Gliosis
KW - Humans
KW - Magnetic Resonance Imaging
KW - Nerve Degeneration
KW - Rats
U2 - 10.1002/ar.20995
DO - 10.1002/ar.20995
M3 - Article
C2 - 19943341
SN - 1932-8494
VL - 292
SP - 1882
EP - 1892
JO - Anatomical record (Hoboken, N.J. : 2007)
JF - Anatomical record (Hoboken, N.J. : 2007)
IS - 12
ER -