White matter changes in the gerbil brain under chronic cerebral hypoperfusion.

Abstract

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. 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. 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. 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.