Intra-carotid arterial transfusion of circulatory-derived autologous endothelial progenitor cells in rodent after ischemic stroke — evaluating the impact of therapeutic time points on prognostic outcomes

2020 ◽  
Author(s):  
Kun-Chen Lin ◽  
Han-Tan Chai ◽  
Kuan-Hung Chen ◽  
Pei‐Hsun Sung ◽  
John Y. Chiang ◽  
...  

Abstract Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x106 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.

2020 ◽  
Author(s):  
Kun-Chen Lin ◽  
Han-Tan Chai ◽  
Kuan-Hung Chen ◽  
Pei‐Hsun Sung ◽  
John Y. Chiang ◽  
...  

Abstract Background: This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results: Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x10 6 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day-14 IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (BIV) (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial cell markers at protein and cellular levels, and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein and cellular levels of inflammation, and protein levels of oxidative stress, autophagy and apoptosis, were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein and cellular levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 4 to 7 (all p<0.0001). Conclusion: Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.


2020 ◽  
Author(s):  
Kun-Chen Lin ◽  
Han-Tan Chai ◽  
Kuan-Hung Chen ◽  
Pei‐Hsun Sung ◽  
John Y. Chiang ◽  
...  

Abstract Background This study tested the optimal time point for left intra-carotid arterial (LICA) administration of circulatory-derived autologous endothelial progenitor cells (EPCs) for improving the outcome in rat after acute ischemic stroke (IS). Methods and Results Adult-male SD rats (n=70) were equally categorized into group 1 (sham-operated control), group 2 (IS), group 3 (IS+EPCs/1.2x10 6 cells/by LICA administration 3h after IS), group 4 (IS+EPCs/LICA administration post-day-3 IS), group 5 (IS+EPCs/LICA administration post-day-7 IS), group 6 (IS+EPCs/LICA administration post-day 14-IS) and group 7 (IS+EPCs/LICA administration post-day-28 IS). The brain-infarct volume (at day 60/MRI) was lowest in group 1, highest in group 2 and significantly progressively increased from groups 3 to 7, whereas among the IS animals, the neurological function (i.e., by corner test) was significantly preserved in groups 3 to 6 than in groups 2 and 7 post-day-60 IS (all p<0.0001). By day 60, the endothelial markers at protein (CD31/vWF) and cellular levels (CD31+/vWF+), and number of small vessels exhibited an opposite pattern of BIV among the groups (all p<0.0001). The protein (IL-1ß/TNF-α/p-NF-κB/MMP-9) and cellular (GFAP+/microglial+) inflammatory levels, oxidative stress (NOX-1/NOX-2/oxidized protein/p22phox), autophagic (LC3B-III/LC3B-I/Beclin-1/Atg-5) and apoptotic (mitochondrial-Bax/caspase-3/PARP), were highest in group 2, lowest in group 1 and progressively increased from groups 3 to 7 (all p<0.0001). The angiogenesis biomarkers at protein (VEGF/SDF-1α/CXCR4) and cellular (SDF-1α+/CXCR4+) levels were significantly progressively increased from groups 1 to 3, then significantly progressively decreased from groups 3 to 7 (all p<0.0001).Conclusion Early EPC administration provided better benefits on improving functional/image/molecular-cellular outcomes after acute IS in rat.


2021 ◽  
Vol 74 (8) ◽  
pp. 1910-1916
Author(s):  
Oleksandr O. Pushko

The aim: Was to evaluate the impact of active rehabilitation treatment in the scheme of comprehensive therapy of patients with cerebral hemispheric ischemic stroke on the dynamics of recovery of cognitive and psychoemotional disorders, as well as to study their correlations. Materials and methods: The study involved 138 patients: 30 apparently healthy individuals (control group, CG, n = 30) without acute cerebrovascular disorders (anamnestic and neuroimaging), of whom 53.33% were men (n = 16) and 46.67% women (n = 14), the average age of patients in the group was 57.9 ± 1.45 years; 108 people diagnosed with cerebral hemispheric ischemic stroke (n = 108), of whom 62.96% were men (n = 68) and 37.04% women (n = 40), the average age of patients in the group was 58.4 ± 0.76 years. The neurocognitive assessment was performed using the international standardized scales: MMSE, MoCa were used to assess the cognitive sphere, and BDI, STAI (STAI SA, STAI TA) were used to assess psychoemotional disorders. Results: Patients in the comprehensive treatment scheme were additionally prescribed and given two courses of rehabilitation treatment using active rehabilitation methods after the first and third examinations, recovery of cognitive and psychoemotional disorders was significantly faster and better than in group 1, where “classical” measures were applied with the predominance of medicinal therapy. Thus, the average score on the MoCa scale during examination on days 3-7 after cerebral hemispheric ischemic stroke in group 1 was 19.71 ± 0.62 points, in group 2 – 19.17 ± 0.54 points, and during evaluation after 6 months in group 2 – 24.72 ± 0.26 points against 22.19 ± 0.41 points (p <0.0001) in group 1. According to the MMSE scale during examination on days 3-7 after cerebral hemispheric ischemic stroke, the average indicator in group 1 was 22.56 ± 0.43 points, in group 2 – 22.47 ± 0.37 points, and when evaluated after 6 months in group 2 – 25.83 ± 0.23 points against 24.35 ± 0.27 points (p = 0.0001) in group 1. Conclusions: The use of methods for active rehabilitation in the treatment of patients in acute and recovery periods of cerebral hemispheric ischemic stroke significantly contributes to the acceleration and enhancement of the recuperation of cognitive and psychoemotional functions after the acute cerebral accident. The obtained results can find practical application in improving the effectiveness of therapeutic and rehabilitation programs in patients with cerebral hemispheric ischemic stroke to reduce their post-stroke deficit.


2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Yongfang Wang ◽  
Ke Ren ◽  
Lizhi Xie ◽  
Wenge Sun ◽  
Yi Liu ◽  
...  

Purpose. To determine the optimal time interval of repeated intravenous injections of iodixanol in rat model and to identify the injury location and causes of renal damage in vivo. Materials and Methods. Rats were randomly divided into Control group, Group 1 with one iodixanol injection, and Group 2 with two iodixanol injections. Group 2 was subdivided into 3 cohorts according to the interval between the first and second iodixanol injections as 1, 3, and 5 days, respectively. Blood oxygen level-dependent (BOLD) imaging and diffusion weighted imaging (DWI) were performed at 1 hour, 1 day, 3 days, 5 days, and 10 days after the application of solutions. Results. Compared with Group 1 (7.2%), Group 2 produced a remarkable R2⁎ increment at the inner stripe of the renal outer medulla by 15.37% (P=0.012), 14.83% (P=0.046), and 13.53% (P>0.05), respectively, at 1 hour after repeated injection of iodixanol. The severity of BOLD MRI to detect renal hypoxia was consistent with the expression of HIF-1α and R2⁎ was well correlated with HIF-1α expression (r=0.704). The acute tubular injury was associated with urinary NGAL and increased significantly at 1 day. Conclusions. Repetitive injection of iodixanol within a short time window can induce acute kidney injury, the impact of which on renal damage in rats disappears gradually 3–5 days after the injections.


Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yip Hon-Kan

Background and Purpose Endothelial progenitor cells (EPCs) migrate from bone marrow to systemic circulation in response to tissue ischemia where they differentiate into mature endothelial cells for in situ angiogenesis. This study tested the hypothesis that the level of circulating EPCs is substantially increased and predictive of prognostic outcomes after acute ischemic stroke. Methods The level of circulating EPCs [staining markers: CD31/CD34 (E 1 ), CD62E/CD34 (E 2 ) and KDR/CD34 (E 3 )] was examined using flow cytometry at 48 h after acute ischemic stroke in 138 consecutive patients. The EPC level was also evaluated once in twenty healthy volunteers and in forty at-risk controls. Results Level of circulating EPCs (E 1–3 ) was significantly higher in ischemic stroke patients than in at-risk control subjects ( p <0.05). Additionally, EPC (E 1–3 ) level was significantly lower in patients with severe neurological impairment [defined as a score ≥12 on the National Institute of Health Stroke Scale (NIHSS)] than in patients with less severe impairment (NIHSS < score 12) at 48 h after ischemic stroke ( p <0.0001). Moreover, the EPC (E 3 ) level was strongly correlated with improved NIHSS ≥ 4 on day 21 after ischemic stroke ( p =0.0004). Furthermore, low circulating EPC level was independently predictive of severe neurological impairment (NIHSS ≥ 12) at 48 h (E 1–3 ) and combined major adverse clinical outcomes (defined as recurrent ischemic stroke, any cause of death, or NIHSS of ≥ 12) on day 90 (E 1 ) following ischemic stroke ( p <0.001). Conclusions Level of circulating EPCs is independently predictive of prognosis after ischemic stroke.


2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  

For this study, peripheral blood samples were collected from human volunteers. Mononuclear cells (MNC) were separated by density centrifugation and were induced to differentiate into endothelial progenitor cells (EPCs) in vitro. Different concentrations of rapamycin and silymarin were introduced to the EPCs over 24 hours and then EPCs were analyzed for proliferation, migration, apoptosis and angiogenesis. Compared with the control group, rapamycin (1, 10, 100 ng/mL) inhibited the proliferation and migration of EPCs in a concentration dependent manner ( P<0.05). Silymarin (50, 100 μg/mL) enhanced the proliferation and migration of EPCs and inhibited apoptosis in a concentration dependent manner ( P<0.05). By adding rapamycin (1 ng/mL) and silymarin (25, 50, 100 μg/mL) over 24 hours, silymarin inhibited the pro-apoptotic effect of rapamycin on EPCs, and reversed the inhibition of proliferation, migration and angiogenesis of EPCs by rapamycin ( P<0.05).


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