Biomedical subjects

Shiow-Jiuan Lin

Publications and source records attributed to Shiow-Jiuan Lin.

4 recordsLinked to original sources

PubMed2005

Demyelination increases radial diffusivity in corpus callosum of mouse brain.

Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axonal conduction and can also be associated with axonal degeneration. Accurate assessments of these conditions may be highly beneficial in evaluating and selecting therapeutic strategies for patient management. Recently, an analytical approach examining diffusion tensor imaging (DTI) derived parameters has been proposed to assess the extent of axonal damage, demyelination, or both. The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability of DTI parameters to detect the progression of myelin degeneration and regeneration. Our results demonstrate that the extent of increased radial diffusivity reflects the severity of demyelination in corpus callosum of mouse brain affected by cuprizone treatment. Subsequently, radial diffusivity decreases with the progression of remyelination. Furthermore, radial diffusivity changes were specific to the time course of changes in myelin integrity as distinct from axonal injury, which was detected by betaAPP immunostaining and shown to be most extensive prior to demyelination. Radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage.

Algorithms↗

PubMed2005

Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging.

Using magnetic resonance diffusion tensor imaging (DTI), the present study investigates changes in both gray and white matter in the APPsw transgenic mouse (Tg2576), a model of beta-amyloid plaque deposition associated with Alzheimer's disease (AD). DTI analyses were performed in cross-sectional groups of transgene-positive and -negative mice at 8, 12, 16, and 18 months of age to assess the magnitude of water diffusion in gray matter (i.e., Tr(D)) and changes in diffusion in white matter that may be indicative of axonal degeneration (i.e., reduced water diffusion parallel to axonal tracts, lambda(||)) and myelin degradation (i.e., increased water diffusion perpendicular to axonal tracts, lambda(perpendicular)). No appreciable changes in gray or white matter were observed between the APPsw and the age-matched control mice at 8 months of age. Reduced Tr(D) and lambda(||) were observed in gray and white matter, respectively, for the APPsw mice at ages greater than 8 months, which coincides with the time period when appreciable amyloid plaque accumulation was confirmed by ex vivo histopathological studies. The decreases in lambda(||) suggest the presence of axonal injury in multiple white matter tracts of APPsw mice. Unlike lambda(||), lambda(perpendicular) was unaltered between control and APPsw mice in most white matter tracts. However, in the corpus collosum (CC), lambda(perpendicular) increased at 16 and 18 months of age, suggesting the possibility of myelin damage in the CC at these later ages. This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues.

Aging↗

PubMed2004

Diffusion tensor imaging detects age-dependent white matter changes in a transgenic mouse model with amyloid deposition.

Increasing evidence demonstrates that there is marked damage and dysfunction not only in the gray matter but also in the white matter in Alzheimer's disease (AD). In this study, transgenic mice overexpressing beta-amyloid precursor protein (APP) under control of the platelet-derived growth factor promoter (PDAPP mice) were examined using diffusion tensor magnetic resonance imaging (DTI) to evaluate the extent of white matter injury before and following the development of AD-like pathology. The profile of DTI parameters was significantly different in old PDAPP mice compared to that of old control mice following the development of AD-like pathology. No difference in DTI parameters was observed between the young PDAPP and control mice. Our results suggest that as amyloid beta (Abeta) deposition and levels increase over time in PDAPP mice, these changes lead to primary or secondary white matter injury that can be detected by DTI.

Aging↗

PubMed2003

Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia.

Both axon and myelin degeneration have significant impact on the long-term disability of patients with white matter disorder. However, the clinical manifestations of the neurological dysfunction caused by white matter disorders are not sufficient to determine the origin of neurological deficits. A noninvasive biological marker capable of detecting and differentiating axon and myelin degeneration would be a significant addition to currently available tools. Directional diffusivities derived from diffusion tensor imaging (DTI) have been previously proposed by this group as potential biological markers to detect and differentiate axon and myelin degeneration. To further test the hypothesis that axial (lambdaparallel) and radial (lambdaperpendicular) diffusivities reflect axon and myelin pathologies, respectively, the optic nerve was examined serially using DTI in a mouse model of retinal ischemia. A significant decrease of lambdaparallel, the putative DTI axonal marker, was observed 3 days after ischemia without concurrently detectable changes in lambdaperpendicular, the putative myelin marker. This result is consistent with histological findings of significant axonal degeneration with no detectable demyelination at 3 days after ischemia. The elevation of lambdaperpendicular observed 5 days after ischemia is consistent with histological findings of myelin degeneration at this time. These results support the hypothesis that lambdaparallel and lambdaperpendicular hold promise as specific markers of axonal and myelin injury, respectively, and, further, that the coexistence of axonal and myelin degeneration does not confound this utility.

Animals↗