White Matter Changes in the Gerbil Brain Under Chronic Cerebral Hypoperfusion

Abstract

Background and Purpose-An animal model of chronic cerebral hypoperfusion was developed with coiled clips applied to both carotid arteries of adult Mongolian gerbils for between 1 week and 2 months. In the brain of this animal model, rarefaction of white matter with dilatation of the ventricles was frequently observed. To better understand the mechanism of white matter alteration under cerebral hypoperfusion, the chronological sequence of molecular changes in the cerebral white matter of the animal model was determined. Methods-Specially designed coiled clips were placed around both carotid arteries of Mongolian gerbils to create stenosis without occlusion. Changes in levels of myelin basic protein (MBP) as a marker of myelin, neurofilament H (NFH) as a marker of axonal proteins, and glial fibrillary acidic protein (GFAP) in astroglia after 2 months of cerebral hypoperfusion were analyzed with Western blotting and enzyme-linked immunosorbent assay. Results-Western blotting of the white matter after 2 months of hypoperfusion showed that the levels of MBP and NFH decreased, whereas that of GFAP increased. The time course of MBP and NFH changes determined with enzyme-linked immunosorbent assay revealed that the change of MBP preceded that of NFH. Conclusions-In the present study it was shown that the damage to myelin precedes that to the axon in the white matter in a chronic cerebral hypoperfusion animal model, suggesting that the change in myelin is the primary pathological event in the cerebral white matter under chronic hypoperfusion. The present study may help in understanding the mechanisms of white matter pathology in leukoaraiosis.

Characteristics of Diffusional Kurtosis in Chronic Ischemia of Adult Moyamoya Disease: Comparing Diffusional Kurtosis and Diffusion Tensor Imaging

“…In an experimental animal model of chronic white matter ischemia, damage to myelin preceded axonal damage, suggesting that the change in myelin is the primary pathologic event. 30 Our observation of a stronger correlation between AK, rather than AD, and general intellectual ability measured by the Wechsler Adult Intelligent Scale-III may imply that a reduction in axonal density and/or axonal degeneration, a more advanced stage of chronic ischemic injury, is better described by AK than AD. Previous investigations by using DTI and probabilistic tractography have shown correlations between neuropsychological examinations and the FA of subcortical white matter.…”

Impaired Cerebrovascular Reactivity With Steal Phenomenon Is Associated With Increased Diffusion in White Matter of Patients With Moyamoya Disease

“…In experimental models of chronic hypoperfusion, WM appears particularly vulnerable, undergoing rarefaction with demyelination, axonal loss, and gliosis. 22,23 Our results suggest that subtle ischemic changes may be present in regions of steal phenomenon in the normal-appearing WM of patients with Moyamoya disease, leading to increased ADC in these areas. We also found increased ADC within foci of WMH on FLAIR images, in agreement with previous studies.…”

Brain macrostructural and microstructural abnormalities in cocaine dependence

“…Western blotting was used to examine the molecular changes in WM following chronic hypoperfusion. Myelin basic protein (MBP), a marker for myelin, was low; neurofilament H (NFH), a marker of axons, was decreased; and glial fibrillary acidic protein, a marker of astroglia, was increased (Kurumatani et al, 1998). The decrease in MBP preceded the decrease in NFH, leading the authors to conclude that the change in myelin is the primary pathological event in cerebral WM under chronic hypoperfusion.…”