ABSTRACT
Objective To investigate the correlation between the indicators of common carotid artery mechanical dynamics, a circumferential wal tension (CWT) and a shear stress (SS), and cerebral smal vessel disease (SVD). Methods The neurological outpatients without obvious cardiovascular disease were enrol ed consecutively. The inner diameters of carotid arteries and blood flow velocity of the patients w ere measured by ultrasound examination, and their CWT and SS w ere calculated. Lacunar infarction and/or leukoaraiosis w ere determined according to the findings of MRI. Results A total of 296 patients w ere enrol ed, 163 of them had lacunar infarction and 132 had leukoaraiosis. Univariate analysis show ed that there w ere significant differences in the distributions of age, hypertension, diabetes, systolic blood pressure, diastolic blood pressure, CWT, and SS betw een the lacunar infarction group and the non-lacunar infarction group, as wel as between the leukoaraiosis group and the non-leukoaraiosis group (al P<0.05). After adjusting for relevant risk factors, multivariate logistic regression analysis show ed that the peak systolic CWT (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.48-8.30) and end diastolic CWT (OR 1.22, 95%CI 1.21-1.25) w ere the independent risk factors for lacunar infarction, w hile the peak systolic SS (OR 0.90, 95%CI 0.75-0.95 ) and end diastolic SS ( OR 0.87, 95%CI 0.84-0.98 ) w ere the independent protective factors for lacunar infarction; the peak systolic CWT (OR 4.67, 95%CI 2.05-10.52) and end diastolic CWT (OR 1.25, 95%CI 1.22-1.47) were the independent risk factors for leukoariosis, w hile the peak systolic SS (OR 0.93, 95%CI 0.75-0.94) and end diastolic SS (OR 0.91, 95%CI 0.85-0.98) w ere the independent protective factors for leukoaraiosis. Conclusions The common carotid artery mechanical stress w as associated w ith the occurrence of SVD.
ABSTRACT
Objective To investigate the relationship between the expression changes of p-Akt (Ser473),p-Bad (Ser136) and the cell apoptosis in peri-infarction tissue of permanent middle cerebral artery occlusion (MCAO) in rats.Methods Sixty male Sprague-Dawley rats were randomly allocated into sham operation,MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h,and LY294002 intervention MCAO 12 h groups (n =12 in each group).A permanent MCAO model was induced by the modified suture method.At 15 minutes before modeling,the rats in the LY294002 intervention MCAO groups were administered via lateral ventricle.The neurological function score was scored by using Zea Longa method.2,3,5-triphenyltetrazolium chloride (TTC) staining was used to detect infarct volume.Immunohistochemical staining was use to detect pAkt (Ser473) and p-Bad (Ser136) expressions in peri-infaretion tissue.TUNEL assay was used to detect apoptotic cells in peri-infarction tissue.Results Three hours after modeling all the experimental rats awoke from anesthesia.The neurological deficit score in the sham operation group was 0,and the scores of the MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h and LY294002 intervention MCAO 12 h groups were 2.25 ± 0.45,2.92 ± 0.99,3.00 ± 0.95,and 3.02 ± 0.36,respectively.There were significant differences among all groups (F =26.520,P =0.000).The score of the LY294002 intervention MCAO 3 h group was significantly higher than that of the MCAO 3 h group (P =0.009).There was no significant difference between the LY294002 intervention MCAO 12 h group and the MCAO 12 h group (P =0.354).TTC staining showed that no infarct was observed in the sham operation group.The infarct volumes of the MCAO 3 h,MCAO 12 h,LY294002 intervention MCAO 3 h and LY294002 intervention MCAO 12 h groups were 23.4 ± 1.4,40.3 ± 1.1,31.9 ±6.0 and 44.4 ±3.8 mm3,respectively.There were significant differences among the groups (F =30.440,P =0.000).The score of the LY294002 intervention MCAO 3 h group was significantly greater than that of the MCAO 3 h group (P =0.002).There was no significant difference between the LY294002 intervention MCAO 12 h group and the MCAO 12 h group (P=0.113).Compared with the sham operation group,the p-Akt (Ser473) expression in peri-infarction tissue in the MCAO 3 h group was significantly high,and it was significantly decreased in the MCAO 12 h group; the expression level of p-Bad (Ser136) showed a progressive decline with the passage of MCAO time,at the same time,the number of apoptotic cells increased progressively.After the LY294002 intervention,the expression levels of p-Akt (Ser473) and p-Bad (Ser136) in peri-infarction tissue decreased significantly at 3 h after MCAO,and the number of apoptotic cells increased significantly (P ＜0.05),but there was no significant effect on each index at 12 h after MCAO.Conclusions The activation of the PI3K/Akt signal transduction pathway in early cerebral infarction and the stress elevation of the key protein p-Akt (Ser473) of this pathway have brain protection,while the failure of this pathway activity and the drastical decrease of its key protein in the late cerebral infarction are associated with brain injury.
ABSTRACT
Apoptosis is one of the important forms during cerebral ischemia.Phosphoinositide-3 kinase (PI3K)/serine/threonine kinase (Akt) is the important cell survival signaling pathway,while c-jun N-terminal kinase (JNK) is the important pro-apoptotic signaling pathway.The dynamic equilibrium of the two signal transduction pathways maintains cell survival and apoptosis under the physiological state.Stimulation during cerebral ischemia breaks this physiological balance and results in the apoptosis of massive neurons.A variety of proved neuroprotective factors are associated with the amplification of enhancement of cell survival signal or inhibition of apoptosis signal,and thrus maintain the balance between the two signal pathways.