Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging.
Diffusion tensor magnetic resonance imaging (DT-MRI) was applied for in vivo quantification of myelin loss and regeneration. A transgenic mouse line (Oligo-TTK) expressing a truncated form of the herpes simplex virus 1 thymidine kinase gene (hsv1-tk) in oligodendrocytes was studied along with two induced phenotypes of myelin pathology. Myelin loss and axonal abnormalities differentially affect values of DT-MRI parameters in the brain of transgenic mice. Changes in the anisotropy of the white matter were assessed by calculating and mapping the radial (D perpendicular) and axial (D parallel) water diffusion to axonal tracts and fractional anisotropy (FA). A significant increase in D perpendicular attributed to the lack of myelin was observed in all selected brain white matter tracts in dysmyelinated mice. Lower D parallel values were consistent with the histological observation of axonal modifications, including reduced axonal caliber and overexpression of neurofilaments and III beta-tubulin. We show clearly that myelination and axonal changes play a role in the degree of diffusion anisotropy, because FA was significantly decreased in dysmyelinated brain. Importantly, myelin reparation during brain postnatal development induced a decrease in the magnitude of D( perpendicular) and an increase in FA compared with the same brain before recovery. The progressive increase in D parallel values was attributed to the gain in normal axonal morphology. This regeneration was confirmed by the detection of enlarged oligodendrocyte population, newly formed myelin sheaths around additional axons, and a gradual increase in axonal caliber.
Harsan
Laura A
LA
UMR 7004 CNRS/ULP, Institut de Physique Biologique, Faculté de Médecine,Université Louis Pasteur, Strasbourg, France.
Poulet
Patrick
P
Guignard
Blandine
B
Steibel
Jérôme
J
Parizel
Nathalie
N
de Sousa
Paulo Loureiro
PL
Boehm
Nelly
N
Grucker
Daniel
D
Ghandour
M Said
MS
D000818:Animals; D000831:Animals, Newborn; D016880:Anisotropy; D000998:Antiviral Agents / Q000008:administration & dosage; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D001931:Brain Mapping; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D038524:Diffusion Magnetic Resonance Imaging; D015774:Ganciclovir / Q000008:administration & dosage; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000998:Antiviral Agents; D004676:Myelin Basic Protein; C441620:Ttk protein, mouse; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D015774:Ganciclovir