Protective Effects And Mechanism Of Naomaitai On White Matter In The Brain Of Vascular Dementia Rats

Vascular dementia,a heterogeneous group of brain disorders in which cognitiveimpairment is attributable to cerebrovascular pathologies,is usually caused bycardiovascular diseases such as hypertension,diabetes and genetic factors.Majorclinical manifestations of the disease includes memory and cognitive impairment.With the development of the society,age-related dementia,an irreversible conditionresulting in progressive cognitive decline,has emerged as one of the leading healthproblems of our time,being second only to Alzheimer’s disease.Mostimportantly,there are no approved treatments for VCI and vascular dementia,it isnecessary to invesgate the pathological mechanism. Increasing evidence suggests thatthe white matter lesions is closely associated with cognitive impairment which causedby vascular dementia.And the flow reduction in brain precedes may contribute to thewhite matter damage.Demyelination,activation of microglia,proliferation of astrocytes,apoptosis of oligodendrocytes,increased permability of blood-brain-barrier offenoccurs in the white matter lesion area.Metalloproteinases are a large family of important Zn2+dependentproteases.They are important in neuroinflammation,and recent studies have linkedtheir actions to neurodegenerative disorders.MMPs act as cellsurface sheddases andcan affect cell signalling initiated by growth factors or death receptors.By attackingthe extracellular matrix,gelatinase(MMP2,MMP9) would increase the permeability ofthe blood–brain barrier as part of the neuroinflammatory.In vascular cognitiveimpairment, MMPs change the permeability of blood-brain barrier and mightcontribute to white matter damage.Naomaitai, which consists of ginkgo, carthamus and salvia,is a approvedmedicine largely used for recover from stroke.Recent research had proved Naomaitaicould decrease the permability of blood-brain-barrier by lower the expression ofgelatinase,What’s more, cerebral blood flow alterations have also been influenced by Naomaitai.In a word,by increasing cerebral blood flow Naomaitai would protect thewhite matter in vascular dementia rats. The protective effect might connect withMMPs.The purpose of this study is to explore the relationship between gelatinase and whitematter injury and whether Naomaitai decrease white matter lesions in aMMPs-medicated way. After bilateral clipping of the commoncarotid arteries,Morriswater maze was used to detect the spatial learning and memory ability to make sureNaomaitai would improve congnitive capacity.HE staining indicated white matterlesion, Luxol fast blue staining and immunostaining with anti-MBP revealeddemyelinating changes in the optic tract to investigate the role Naomaitai plays inwhite matter lesions. Immunostaining with anti-iba1and anti-GFAP was applicated toinvestigate the influence of Naomaitai on activation and proliferation of glials.Whitematter lesions are closely associated with cognitive impairment and motordysfunction. To explore the pathophysiology of these lesions,we examined theexpression of matrix metalloproteinase-2and matrix metalloproteinase-9in the whitematter by western blot and immunohistochemical method.We observed increased expression of MMP2in periventricular white matter ofvascular dementia rats，which indicates MMP2be directly involved in the remodelingof the white matter myelin and microvascular beds. In contrast, MMP9expressionwas negligible as determined by its protein levels in the present chronichypoperfusion model.Thus， MMP9might not directly involvedin white matterlesions.After treatment with Naomaitai for6weeks,congnitive abilities had beenimproved.Naomaitai might alleviate degradation of the white matter myelin through aMMP2medicated way.