The Inflammatory Mechanisms Involved In The Influence Of Diabetes Mellitus On Chronic Cerebral Hypoperfusion Induced White Matter Injury

AimThe object of our examination is to explore the influence of type 2 diabetes mellitus on the comorbid chronic cerebral hypoperfusion-injury in the cognitive performance and white matter structure in mice and related mechanisms.MethodsWe applied bilateral common carotid artery stenosis in db/db mice and healthy control mice for 4 weeks,to produce the animal model of chronic cerebral hypoperfusion.We measured cerebral blood flow in mice with cerebral blood flow monitor,cognitive performance with behavioral test,white matter lesions with Luxol Fast blue test,changes in glial cells with immunofluorescence,and inflammatory responses with realtime PCR.ResultsMice from control and db/db group all experienced a sustained cerebral blood flow decline.After BCAS,control mice showed cognitive deficits,white matter lesions,activation in glial cells,decrease in oligodendrocytes and myelin basic protein,elevation in the expression of TNF-?and IL-1?.While after 4 weeks of BCAS,there is no change in the cognitive performance,white matter structure,glial cells and oligodendrocytes in db/db mice,and the elevation of TNF-?and IL-1? was alleviated,besides,there was more expression in anti-inflammatory cytokines IL-10 and IL-4.Further more,IL-1Ra was increased in db/db mice after BCAS.ConclusionsThrough the suppression of glial activation and pro-inflammatory cytokine expression,and the increase of anti-inflammatory cytokines and IL-1Ra,diabetes mellitus alleviates the brain injury caused by chronic cerebral hypoperfusion.