ABSTRACT
ObjectiveTo investigate the associations of plasma homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels with dementia.MethodsThe patients with dementia admitted to hospital were enrolled retrospectively.They were divided into a vascular dementia (VaD) group, a mixed dementia (MD) group, and an Alzheimer's disease (AD) group according to the Hachinski Ischemic Score, and the dementia severity was further divided into a mild group, a moderate group and a severe group according to the Mini-Mental State Examination.The non-demented patients hospitalized during the same period were selected as controls.The demographics, vascular risk factors, and plasma Hcy and Lp-PLA2 levels in each group were compared.Logistic regression analysis was used to determine the independent associations of the plasma Hcy and Lp-PLA2 levels with the risk of dementia and severity.ResultsA total of 125 patients with dementia were enrolled, including 52 (41.6%) in the VaD group, 21 (16.8%) in the MD group, and 53 (41.6%) in the AD group.There were 49 patients (39.2%) in the mild group, 51 (40.8%) in the moderate group, and 25 (20%) in the severe group.A total of 40 non-demented patients were enrolled as control group.The plasma Hcy and Lp-PLA2 levels in VaD, MD and AD groups were significantly higher than those in the control group (all P<0.001).Multivariable logistic regression analysis showed that the advanced age (odds ratio[OR] 1.12, 95% confidence interval [CI] 1.03-1.21;P=0.010), high plasma Hcy level (OR 1.44, 95% CI 1.21-1.71;P<0.001), high Lp-PLA2 level (OR 1.01, 95% CI 1.00-1.02;P=0.006), and previous stroke (OR 4.29, 95% CI 1.50-12.36;P=0.007) were the independent risk factors for dementia;high Hcy level (OR 1.48, 95% CI 1.21-1.82;P<0.001, high Lp-PLA2 level (OR 1.01, 95% CI 1.00-1.03;P=0.002), and previous stroke (OR 152.78, 95% CI 20.41-999.97;P<0.001) were the independent risk factors for VaD;advanced age (OR 1.10, 95% CI 1.02-1.17;P=0.008) and high Hcy level (OR 1.41, 95% CI 1.25-1.58;P<0.001) were the independent risk factor for severe dementia.ConclusionsThe increased plasma Hcy and Lp-PLA2 levels are associated with dementia.Reducing the plasma Hcy and Lp-PLA2 levels may be beneficial to the treatment and prevention of dementia.
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Objective To establish and validate a modified rat thromboembolic stroke model.Methods After taking femoral arterial blood and mixing it with thrombin,they were injected into PE-50 catheter for preparing in vitro thrombosis in 60 Sprague-Dawley rats.A thromboembolic cerebral ischemia model induced by catheterization of the right external carotid artery and the small blood clot emboli were injected into the internal carotid arteries.Thirty rats were randomly divided into a large number of emboli group (n =10 with 12 emboli),a median number of emboli group (n =10 with 10 emboli) and a small number of emboli group (n =10 with 8 emboli).Two hours after embolus injection,the neurological deficit score was performed and the success rate of the model was compared in all groups.Twenty-four hours after embolus injection,the rats were sacrificed and the brains were removed for 2,3,5-triphenyltetrazolium chloride staining.The hemorrhage,infarct volume,bleeding incidence and mortality after cerebral infarction were evaluated.The high success rates of the modeling in the emboli groups were selected and they were randomly divided into either a normal saline group (n =12) or a recombinant tissue-type plasminogen activator (rtPA) group (n =12).The rats were given normal saline and rtPA at 3 hours after embolus injection.Before embolus injection and 2,6,12 and 24 hours after embolus injection,the neurological scores were performed respectively; 24 hours after embolus injection,the rats were sacrificed and the brains were removed for 2,3,5-triphenyltetrazolium chloride staining.The hemorrhage rate,infarction size,degree of cerebral edema,and blood-brain barrier permeability were evaluated.Results Only 40％ of rats had neurological deficits in the small number of emboli group,and the infarct volume was only 10.54 ± 2.82％.The success rates in the median and large number of emboli groups were 80％ and 100％ respectively.They were all significantly higher than those in the small number of emboli group (P =0.011 ).The infarct volume was also significantly greater than that in the small number of emboli group (F =40.897,P =0.000).After administration of rtPA,the mean survival time of the rats in the large number of emboli group was less than 24 hours,so the median number of emboli group was selected to study the thrombolytic effect of rtPA.The infarct volume and neurological function score in the rtPA group were improved significantly compared to the normal saline group (t =7.728,P =0.000),while there were no significant differences in the hemorrhage rate,degree of brain edema and blood-brain barrier permeability between the 2 groups.Conclusions The stability and reproducibility were good in the modified thromboembolic cerebral ischemia model injected with 10 emboli,the neurological function was improved significantly after thrombolysis,and it was applicable to the experimental study of pathophysiology of cerebral ischemia and thrombolytic therapy.
ABSTRACT
Objective To investigate the effects of recombinant tissue plasminogen activator (rt-PA)intravenous thrombolysis on blood-brain barrier (BBB) permeability,the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats.Methods A total of 40 adult male Sprague-Dawley rats were allocated into 3 groups:Sham operation group (n =10),middle cerebral artery occlusion (MCAO) group (n =18),and rt-PA thrombolysis group (n =18).A MCAO model was established by using autologous thromboembolism.The sham operation group did not inject any thromboembolus,the MCAO group only made MCAO,and the rt-PA thrombolysis group received intravenous thrombolysis with rt-PA at 3 hours after MCAO.Brain infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride staining BBB permeability was measured by Evans blue dye leakage.The activities and the expressions of MMP-2 and MMP-9 in brain tissue were detected by Gelatin zymography and Western blot,respectively.Results Compared to the MCAO group,the neurological function was improved significantly in the rt-PA thrombolysis group,and the infarct volume was also reduced significantly (t =7.365,P =0.005).However,the hemorrhage score (t =-3.286,P =0.017) and BBB permeability (t =-3.947,P =0.029) were increased significantly.The activities and the expressions of MMP-2 and MMP-9 in the sham operation group were lower.The activities and the expressions of MMP-2 (t =-45.121,P =0.000; t =-11.624,P=0.000) and MMP-9 (t=-71.849,P=0.000; t=-8.992,P=0.000) in the MCAO group were increased and upregulated significantly.Compared to the MCAO group,the activities and the expressions of MMP-2 (t =-28.792,P =0.000; t =-3.809,P =0.013) and MMP-9 (t =-53.506,P =0.000; t =-2.640,P =0.046) in the rt-PA thrombolysis group were increased and upregulated significantly.Conclusions After rt-PA intravenous thrombolytic therapy,the BBB permeability was increased.The activities and the expressions of MMP-2 and MMP-9 were increased and upregulated.MMP-2 and MMP-9 might participate in the increased BBB permeability,and thus inducing hemorrhagic transformation after rt-PA intravenous thrombolytic therapy in rats with cerebral ischemia.