Periventricular White Matter Changes And Matrix Metalloproteinase-2, 3 And 7 Expressions After Chronic Cerebral Hypoperfusion In Rats

【Background and Purpose】Recently, with the development of the medical imaging technology, white matter lesions( WML) which present studies have shown that it contributes to cognitive impairment and dementia are checked out frequently. Cognitive impairment and dementia has been bringing many serious problems to our families and societies, so it is significant to understand the mechanism of WML. According to previous studies, ischemia emerges as a potential condition for the development of WML, but the specific mechanism is unclear.【Objective】To observe the changes of periventricular white matter and the expressions of MMP-2, MMP-3 and MMP-7 after chronic cerebral hypoperfusion which was induced by permanent staging ligation of both common carotid arteries in rats.【Methods】1. 60 healthy male Wistar rats were used. These rats were randomly divided into three model groups(n=15) and one sham-operated (control) group(n=15). Model of chronic cerebral hypoperfusion was induced by permanent staging ligation of the bilateral common carotid arteries in the rat.2. The pathological changes of periventricular white matter were observed with electron microscope and luxol fast blue(LFB)staining. The activation of astrocytes was assessed with immunohistochemistry staining of GFAP and the content of MBP was determined with Western blotting.3. The expressions of MMP-2, MMP-3 and MMP-7 were measured with immunohistochemisty staining and Western blotting.【Results】 1. Irregular myelin sheaths and degenerating myelinated axon were observed at the ultrastructural level in the corpus callosum and internal capsule of the d20 operated rats. Luxol fast blue(LFB)staining showed the changes of vacuolization and demyelination in the model group rats.2. The expressions of MMP-2,3 and 7 were markedly elevated and the content of MBP was obviously decreased in the corpus callosum and internal capsule of the operated animals. Obvious proliferation hypertrophy of GFAP immunopositive astrocytes were also observed in those tissues. Additionally, the upregulation of MMP-2,3 and 7 had significant relation with periventricular white matter lesions.【Conclusions】1. Progressive periventricular white matter lesions can be induced by permanent staging ligation of the bilateral common carotid arteries in Wistar rat; this model is feasible and economic and can be used in the studies of chronic cerebral ischemia WML.2. The up-regulation of MMP-2,3 and 7 in the periventricular white matter of chronic cerebral hypoperfusion rats may involve in the pathological process of WML.