Changes in the permeability of blood brain barrier and endothelial cell damage after cerebral ischemia

OBJECTIVE： To investigate the effect of endothelial cells on the permeability of blood brain barrier （BBB） after brain injury and its effect mechanism. DATA SOURCES： We searched for the articles of permeability of BBB and endothelial cell injury after brain is- chemia, which were published between January 1982 and December 2005, with the key words of ＂cerebral ischemia damage,blood brain barrier （ BBB）,permeability,effect of endothelial cell （EC） and its variation mechanism＂in English. STUDY SELECTION： The materials were primarily selected. The articles related to the changes in the permeability of BBB and the effect of endothelial cells as well as the change mechanism after cerebral ischemia damage were chosen. Repetitive studies or review articles were excluded. DATA EXTRACTION： Totally 55 related articles were collected, and 35 were excluded due to repetitive or review articles, finally 20 articles were involved. DATA SYNTHESIS： The content or viewpoints of involved literatures were analyzed. Cerebral ischemia had damage for endothelial cells, such as the inflow of a lot of Ca2^＋, the production of nitrogen monoxide and oxygen free radical, and aggravated destruction of BBB. After acceptors of inflammatory mediators on cerebrovascular endothelial cell membrane, such as histamine, bradykinin , 5-hydroxytryptamine and so on are activated, endothelial cells shrink and the permeability of BBB increases. Its mechanism involves in the inflow of extracellular Ca^＋2and the release of intracellular Ca^2＋ in the cells. Glycocalyx molecule on the surface of endothelial cell, having structural polytropy, is the determinative factor of the permeability of BBB. VEGF, intensively increasing the vasopermeability and mainly effecting on postcapillary vein and veinlet, is the strongest known blood vessel permeation reagent. Its chronic overexpression in the brain can lead the destruction of BBB. CONCLUSION： The injury of endothelial cell participants in the pathological mechanism of BBB destruction after cerebral ischemla.

Transfusion of CXCR4-priming endothelial progenitor cells reduces cerebral ischemic damage and promotes angiogenesis and neurogenesis in db/db diabetic mice

Previous studies suggest that reduction and dysfunction of circulating endothelial progenitor cells(EPCs),and dysregulation in stromal cell derived factor-1/CXC-chemokine receptor 4(SDF-1/ CXCR4) axis in diabetes could be therapeutic targets for diabetic ischemic stroke.This study investigated the efficacy of CXCR4-priming EPCs on cerebral repair following ischemic stroke in db/db diabetic mice.Bone marrow derived EPCs from db/+ control mice were transfected with adenovirus(1×10~7 IU) carrying CXCR4(Ad-CXCR4-EPCs)or null(Ad- null-EPCs).The db/db mice were divided into three groups for EPCs injection(2×10~5 cells/100μl): Ad-CXCR4-EPCs,Ad-null-EPCs or saline(vehicle), via tail vein 2 hrs after middle cerebral artery occlusion (MCAO) surgery.Cerebral blood flow(CBF) was measured with laser Doppler flowmeter.Mice were sacrificed at 2 or 7 days thereafter.Level of circulating EPCs was measured by flow cytometry. Ischemic damage,cerebral microvascular density (MVD),angiogenesis and neurogenesis were determined by histological staining with Fluoro-J,CD31, CD31 +BrdU,NeuN +BrdU,GFAP+BrdU,respectively. Results(table) showed:1) Levels of CXCR4 expression were reduced in the brain and EPCs of db/db mice as measured by real-time RT-PCR and western blot analyses(data not shown);2) The level of circulating EPCs was more in the mice treated with Ad-CXCR4-EPCs;3)EPC transfusion improved CBF,increased MVD,angiogenesis and neurogenesis in peri-infarct area,and decreased ischemic damage.The efficacies were better in Ad-CXCR4 -EPCs group.Data suggest that transfusion of Ad-CXCR4-EPCs could be a therapeutic avenue for ischemia stroke in diabetes.

Effects of salvianolic acids on endothelial cells against damage induced by cholestane-3β-5α-6β-triol

To investigate the effects of salvianolic acids on human umbilical vein endothelial cells (HUVEC) against damage induced by cholestane-3β-5α-6β-triol (chol-triol) Methods The viability of HUVEC was measured by MTT method The apoptosis of HUVEC induced by chol-triol was detected by flow cytometry and TUNEL assay The production of malondialdehyd (MDA) in HUVEC was tested by thiobarbaturic acid (TBA) assay Results The viability of HUVEC treated with chol-triol 100 μmol/L decreased by 39 8% while salvianolic acids 100 μg/ml increased by 27 9% The apoptotic rate of HUVEC measured by PI staining increased from 6%-8% to 17%-20% after chol-triol treatment for 12 h Salvianolic acids 100 μg/ml reduced the apoptotic rate to 10%-14% after treatment HUVEC for 1 h prior to chol-triol treatment In another experiment, chol-triol increased the number of TUNEL-positive cells 5 times, but salvianolic acids 10 μg/ml and 100 μg/ml reduced the number of TUNEL-positive cells by 36 9% and 61 2%, respectively The production of MDA in HUVEC increased by 120 7% after chol-triol treatment for 12 h Salvianolic acids 10 μg/ml and 100 μg/ml also decreased the concentration of MDA by 28 7% and 39 8%, respectively Conclusion Salvianolic acids has protective effect on endothelial cells against damage induced by chol-triol

Clinical Study on Protective Effect of Xinmaitong Capsule on Damage of Vascular Endothelial Cells

Objective: To assess the effect of Xinmaitong (XMT) capsule in treating coronaryheart disease (CHD). Methods: Thirty-eightpatients of coronary heart disease with myocardial ischemia were divided randomly intoXMT group (20 cases) and control group (18cases). Conventional western medical therapywas given to both groups and the XMT groupreceived additional XMT treatment. Thechanges of endothelin (ET ) and calcitoningene-related peptide (CGRP) levels, ST segment of ECG and clinical symptoms aftertreatment in all the patients were observed.Data of 14 healthy persons were taken as normal control. Results: The ET level of all patients was significantly higher than that of thenormal control (P < 0. 001 ), and level ofCGRP in patients was not different from normal control significantly (P > 0. 05 ). Aftertreatment, results showed that: (1 ) The ETlevels and the scores of clinical symptoms ofboth groups decreased significantly (P <0. 01 ), and ST segment elevated markedly(P< 0. 01) as compared with before treatment, and the changes revealed more evidentin XMT group in comparison with those of thecontrol group (P < 0.05 - 0.01 ). (2 ) Thelevel of CGRP was significantly increased inXMT group (P < 0. 01 ) while unchanged inthe control group (P > 0. 05 ). Conclusions:There is severe damage of vascular endothelialcells in CHD patients. XMT could not only reduce significantly the plasma ET content, butalso enhance markedly the production and release of CGRP, so it has a good anti--ischemiceffect, which may be closely related with itsaction on improving the function of vascularendothelial cells and regulating metabolism ofET and CGRP.