WHITE-MATTER CHANGES IN THE GERBIL BRAIN UNDER CHRONIC CEREBRAL HYPOPERFUSION

Background and Purpose-An animal model of chronic cerebral hypoperfusi on 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 mecha nism of white matter alteration under cerebral hypoperfusion, the chro nological sequence of molecular changes in the cerebral white matter o f the animal model was determined. Methods-Specially designed coiled c lips were placed around both carotid arteries of Mongolian gerbils to create stenosis without occlusion. Changes in levels of myelin basic p rotein (MBP) as a marker of myelin, neurofilament H (NFH) as a marker of axonal proteins, and glial fibrillary acidic protein (GFAP) in astr oglia after 2 months of cerebral hypoperfusion were analyzed with West ern blotting and enzyme-linked immunosorbent assay. Results-Western bl otting 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 i mmunosorbent assay revealed that the change of MBP preceded that of NF H. Conclusions-In the present study it was shown that the damage to my elin precedes that to the axon in the white matter in a chronic cerebr al hypoperfusion animal model, suggesting that the change in myelin is the primary pathological event in the cerebral white matter under chr onic hypoperfusion. The present study may help in understanding the me chanisms of white matter pathology in leukoaraiosis.