1.Circulating endothelial progenitor cells in traumatic brain injury: an emerging therapeutic target?
Hui-jie WEI ; Rong-cai JIANG ; Li LIU ; Jian-ning ZHANG
Chinese Journal of Traumatology 2010;13(5):316-318
Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations. In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBI in the future.
Blood-Brain Barrier
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Brain Injuries
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physiopathology
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therapy
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Endothelial Cells
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cytology
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Humans
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Neurogenesis
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Stem Cells
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physiology
5.Perihematomal endothelin-1 level is associated with an increase in blood-brain barrier permeability in a rabbit model of intracerebral hematoma.
Li-Kun WANG ; Zhen HONG ; Guo-Feng WU ; Chang LI
Chinese Medical Journal 2013;126(18):3433-3438
BACKGROUNDEndothelin-1 (ET-1) has deleterious effects on water homeostasis, cerebral edema, and blood-brain barrier (BBB) integrity. Highly expressed ET-1 was observed after intracerebral hemorrhage (ICH); however, ET-1 changes and their relationship with BBB disruption within 24 hours of ICH have not been thoroughly investigated. The aim of the present study was to observe the changes in perihematomal ET-1 levels in various phases of ICH and their correlation with the BBB integrity in a rabbit model of ICH.
METHODSTwenty-five rabbits (3.2-4.3 kg body weight) were randomly divided into a normal control group (five rabbits) and a model group (20 rabbits). Animals in the model group were equally divided into four subgroups (five rabbits each to be sacrificed at 6, 12, 18, and 24 hours following ICH establishment). An ICH model was prepared in the model group by infusing autologous arterial blood into the rabbit brain. ET-1 expression in perihematomal brain tissues was determined using immunohistochemistry and color image analysis, and the permeability of the BBB was assayed using the Evan's Blue (EB) method. A repeated measures analysis of variance was used to make comparisons of the ET-1 and EB content across the entire time series.
RESULTSThe number of perihematomal endothelial cells with ET-1 positive expressions following 6, 12, 18, and 24 hours ICH model establishment was 9.32, 13.05, 15.90, and 20.44, respectively, but as low as 6.67 in the control group. The average transmittance of ET-1-positive cell bodies at 6, 12, 18, and 24 hours after ICH was 99.10, 97.40, 85.70, and 80.80, respectively, but 100.12 in the control group. These data reveal that the expression of ET-1 was significantly increased at 6, 12, 18, and 24 hours after ICH compared with the control group, and a marked decrease in the average transmittance of ET-1-positive cell bodies was noted (P < 0.05). Similarly, the perihematomal EB content at 6, 12, 18, and 24 hours after ICH was 29.39 ± 1.16, 32.20 ± 0.73, 33.63 ± 1.08, and 35.26 ± 1.12, respectively, in the model group and 28.06 ± 0.80 in the control group. The results indicate that a significant increase in the EB content in the model group was observed compared with that of the control group (P < 0.05). Moreover, a positive correlation between the number of ET-1-positive endothelial cells and BBB permeability was observed (r = 0.883, P < 0.05).
CONCLUSIONSHigh levels of ET-1 are closely associated with BBB disruption. ET-1 may play an important role in the pathogenesis of secondary brain injury after ICH.
Animals ; Blood-Brain Barrier ; metabolism ; physiopathology ; Brain ; metabolism ; physiopathology ; Cerebral Hemorrhage ; metabolism ; physiopathology ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Immunohistochemistry ; Male ; Rabbits
6.Photomacrography of brain surface for evaluating blood-brain barrier disruption within 24 h after focal cerebral ischemia in mice.
Li-ping CHEN ; Hui-min XU ; Wei ZHAO ; Shi-hong ZHANG ; Zhao-yang ZHU ; Qi ZHANG ; Guo-liang YU ; Sheng-li CHU ; Er-qing WEI
Journal of Zhejiang University. Medical sciences 2005;34(6):523-528
OBJECTIVETo establish a new photomacrographic analysis of morphological changes on brain surface to evaluate blood-brain barrier (BBB) disruption.
METHODSPermanent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice. Brains were removed 10 min, 0.5, 1, 3, 6, 12 and 24 h after MCAO. The whole brains and brain slices were photographed by a digital camera. BBB disruption was evaluated by hemorrhage and traced Evans blue (EB) on the brain surface. Fluoremetric quantitation of EB and water content in the brains were also performed at various time points.
RESULTPhotomacrographic morphological analysis showed that hemorrhage and traced EB on the surface of the brains significantly increased from 3 h after focal cerebral ischemia,which were correlated to the results in the brain slices. EB content in the ischemic hemispheres was significantly increased from 0.5 h after MCAO, and water content was increased from 1 h after MCAO.
CONCLUSIONPhotomacrographic measurement is a simple and useful method for evaluating BBB disruption semi-quantitatively, and can detect BBB disruption earlier after focal cerebral ischemia in mice.
Animals ; Blood-Brain Barrier ; physiopathology ; Brain ; physiopathology ; Evans Blue ; Infarction, Middle Cerebral Artery ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Photography ; Time Factors
7.Establishment of a method for detecting peripheral blood circulating brain microvascular endothelial cells, a novel biomarker for blood-brain barrier injury.
Yan LI ; Lei DU ; Lin YUAN ; Dexi CHEN ; Jiawen QIU ; Xiaolong HE ; Hong CAO ; Shenghe HUANG
Journal of Southern Medical University 2014;34(12):1733-1737
OBJECTIVETo establish a method for detecting circulating brain microvascular endothelial cells (cBMECs), a novel biomarker of blood-brain barrier (BBB) injury.
METHODSBlood samples were collected from 33 patients with AIDS encephalitis and 13 healthy subjects for detection of cBMECs, cECs and EPCs using magnetic affinity isolation and immune identification technology.
RESULTSThe numbers of cBMECs, cECs and EPCs were significantly higher in the AIDS patients than in the control subjects (t=4.298, P<0.01; t=4.886, P<0.01; t=4.889, P<0.01). An significant association was also noted between HIV load and cBMEC number (r=0.928, P<0.01).
CONCLUSIONWe have successfully established a method for detecting peripheral blood cBMECs, which can be of important value in non-invasive assessment of BBB injury.
Acquired Immunodeficiency Syndrome ; physiopathology ; Biomarkers ; Blood-Brain Barrier ; pathology ; Cell Separation ; methods ; Cells, Cultured ; Endothelial Progenitor Cells ; cytology ; Humans
8.Change of the serum interleukin 6 in patients with delayed encephalopathy after acute carbon monoxide poisoning.
Ren-jun GU ; Xia-hong WANG ; Ping ZHANG ; Hong LU ; Xin-sheng GUO ; Jing-gui SONG ; Fan ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(6):461-462
Acute Disease
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Adult
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Aged
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Blood-Brain Barrier
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physiopathology
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Brain Diseases
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blood
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chemically induced
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Carbon Monoxide Poisoning
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complications
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Female
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Humans
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Interleukin-6
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blood
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Male
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Middle Aged
9.Effect of progesterone on MMP-3 expression in neonatal rat brain after hypoxic-ischemia.
Chun-Yang XU ; Shuang LI ; Xin-Qiang LI ; Dong-Liang LI
Chinese Journal of Applied Physiology 2010;26(3):370-373
OBJECTIVETo study the effect of progesterone on matrix metalloproteinase-3 (MMP-3) expression in neonatal rat brain after hypoxic-ischemia.
METHODSFollowed the hypoxic-ischemia of neonatal rat brain, Evans blue (EB) staining and transmission electron microscopy were used to detect the blood-brain barrier pathological changes on permeability. MMP-3 protein expression in cerebral cortex was measured with Western blot.
RESULTSTransmission electron microscopy results showed that the blood brain barrier in hypoxic-ischemic group changed significantly compare to progesterone group. EB staining results suggested that the blood-brain barrier permeability of hypoxic-ischemic group was significantly increased compared to sham-operated group (P < 0.01). The blood-brain barrier permeability in progesterone group was also decreased in comparison to that of hypoxic-ischemic group (P < 0.05). Western blot image analysis results indicated that MMP-3 protein expression in the hypoxic-ischemic group increased significantly than that in sham-operated group (P < 0.01), and the progesterone group was decreased significantly than that in hypoxic-ischemic group (P < 0.05).
CONCLUSIONProgesterone may reduce the blood-brain barrier damage by reducing MMP-3 expression. This might be one of the protective mechanisms in the hypoxic-ischemic brain injury.
Animals ; Animals, Newborn ; Blood-Brain Barrier ; physiopathology ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; physiopathology ; Matrix Metalloproteinase 3 ; metabolism ; Progesterone ; pharmacology ; Rats ; Rats, Sprague-Dawley
10.Impact of intrauterine infection on long-term brain development of premature rats.
Yun SHANG ; Ling LIU ; Kun-Feng CAO ; Duo-De WANG ; Wei WANG ; Hao XU
Chinese Journal of Contemporary Pediatrics 2010;12(7):569-572
OBJECTIVETo investigate the impact of intrauterine infection induced by LPS injection on long-term brain development of premature rats.
METHODSEighteen day-gestation pregnant rats were randomly assigned to a control group receiving an intraperitoneal injection of normal saline, and two infection groups that were intraperitoneally injected with 0.3 mg/kg or 0.6 mg/kg LPS. Twenty-four hours after injection, 7 pregnant rats of each group were sacrificed. The pathological changes of the placenta after hematoxylin and eosin staining were observed under a light microscope. The neural cell apoptosis of fetal brains was examined by the TUNEL assay. The remained pregnant rats were induced to labour before 21 gestation days. The long-term brain development of premature rats was tested with the Y type electric maze on postnatal day 42.
RESULTSObvious pathological changes were observed in the placenta in the infection groups. The apoptotic neural cells in the fetal brain increased in the infection groups compared with that in the control group (32.41+/-5.36 in the 0.3 mg/kg infection group and 66.41+/-7.61 in the 0.6 mg/kg infection group vs 8.00+/-0.36 in the control group; P<0.01). The number of trials to criterion in the Y type maze test in the infection groups was much more than that in the control group [117.8+/-8.7 (0.3 mg/kg infection group) and 194.4+/-13.7 (0.6 mg/kg infection group) vs 56.8+/-3.7 (control group); P<0.01]. The number of correct reactions in memory retaining in the infection groups was lower than that in the control group (0.62+/-0.09 in the 0.3 mg/kg infection group and 0.37+/-0.09 in the 0.6 mg/kg infection group vs 0.92+/-0.06 in the control group; P<0.05).
CONCLUSIONSIntrauterine infection can cause fetal rats' neural cell apoptosis and affect adversely long-term brain development of neonatal rats.
Animals ; Apoptosis ; Bacterial Infections ; physiopathology ; Blood-Brain Barrier ; Brain ; growth & development ; pathology ; Female ; Maze Learning ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Rats ; Rats, Wistar ; Uterus ; microbiology