scholarly journals Aerobic exercise prevents rarefaction of pial collaterals and increased stroke severity that occur with aging

2017 ◽  
Vol 37 (11) ◽  
pp. 3544-3555 ◽  
Author(s):  
Wojciech Rzechorzek ◽  
Hua Zhang ◽  
Brian K Buckley ◽  
Kunjie Hua ◽  
Daniel Pomp ◽  
...  
Keyword(s):  
Wheel Running ◽  
Infarct Volume ◽  
Inflammatory Marker ◽  
Fold Increase ◽  
Vascular Wall ◽  
Stroke Severity ◽  
Markers Of Inflammation ◽  
Collateral Arteries ◽  
Intracranial Arteries

Variation in extent of the brain’s collateral circulation is an important determinant of variation in the severity of stroke and efficacy of revascularization therapies. However, the number and diameter of pial collateral “arterioles” decrease with aging in associated with reduced eNOS and increased oxidative stress. We tested whether exercise reduces this aging-induced rarefaction. Twelve-month-old mice were randomized to sedentary or voluntary wheel-running. At 26 months’ age, permanent MCA occlusion was followed 72 h later by determination of infarct volume and vascular casting after maximal dilation. The decline in collateral number and diameter and 2.4-fold increase in infarct volume evident in 26-versus 3-month-old sedentary mice were prevented by exercise-training. In contrast, number and diameter of the posterior communicating collateral “arteries” were unaffected by aging or exercise. Interestingly, diameter of the primary intracranial arteries increased with aging. Mechanistically, genetic overexpression of eNOS inhibited age-induced collateral rarefaction, and exercise increased eNOS and SOD2 and decreased the inflammatory marker NFkB assessed in hindlimb arteries. In conclusion, exercise prevented age-induced rarefaction of pial collaterals and reduced infarct volume. Aging also promoted outward remodeling of intracranial arteries. These effects were associated with increased eNOS and reduced markers of inflammation and aging in the vascular wall.

Abstract 222: Exercise Training Prevents Rarefaction of Pial Collaterals, Promotes Cerebral Arterial Remodeling, and Lessens Severity of Stroke in Aging Brain

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wojciech J Rzechorzek ◽  
Brian K Buckley ◽  
Kunji Hua ◽  
Daniel Pomp ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Exercise Training ◽  
Wheel Running ◽  
Important Determinant ◽  
Fiber Type ◽  
Infarct Volume ◽  
Cerebral Arteries ◽  
Aging Brain ◽  
Old Mice

Variation in anatomic extent of the collateral circulation is an important determinant of variation in the severity of ischemic stroke and efficacy of revascularization therapies. Yet pial collateral number and lumen diameter decrease with age, at least in mice. It is not known if this can be mitigated. We tested whether exercise training can accomplish this and if it also affects diameter of the posterior communicating collalterals (PComs) and primary cerebral arteries (ICA, BA, MCA, ACA, PCA). We randomized 30 male and 30 female, 12 months-old (~40 human years, hy) C57BL/6J mice to either sedentary or voluntary wheel-running (daily distance run was measured). At 25 mos-age (~70 hy), permanent MCA occlusion was followed 24h later by vascular casting after maximal dilation and by determination of infarct volume. Controls for aging were 3 mos-old sedentary mice (~16 hy). Training effect was confirmed by muscle fiber-type switching, body weight and cardiac hypertrophy (all p<0.05). Exercise prevented age-associated loss of collateral number and diameter (p=0.049 and 0.005, n=13-14) and reduced infarct volume by 50%, ie, to that seen in 3 months-old mice (p=0.01, n=7). Unlike pial collaterals, PCom diameter and number (ie, present bilaterally, unilaterally or absent) were unaffected by exercise. Of further interest, diameter of the primary cerebral arteries increased with aging alone (119 ± 1 vs 134 ± 5 μm averaged combined diameter, p=0.02, n=10-14); this effect tended to increase further with exercise (143 ± 4 μm, p=0.07, n=13). Mechanistically, exercise increased vascular expression (assessed by immunohisto-chemistry) of total eNOS (p=0.03, n=5-6), phospho-eNOS (p=0.004, n=5) and a marker of anti-oxidative stress (SOD, p=0.008, n=5-6; but not HO-1, p=0.40, n=6). It did not alter a marker of aging (p16, p=0.42, n=5); analysis of additional targets is underway. In conclusion, exercise training prevented age-induced rarefaction of pial collaterals and reduced infarct volume. In addition and unexpectedly, aging also caused outward remodeling of the primary cerebral arteries, and exercise training tended to further augment this. These benefits of regular aerobic exercise were associated with increased eNOS bioavailability and reduced oxidative stress.

scholarly journals P042 Diagnostic and prognostic value of soluble adhesion molecules in patients with ulcerative colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S152-S152
Author(s):  
G Tarasova ◽  
N Dobaeva ◽  
A Iakovlev ◽  
A Volkov
Keyword(s):  
Ulcerative Colitis ◽  
Adhesion Molecules ◽  
Experimental Studies ◽  
Fold Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Moderate Increase ◽  
Soluble Adhesion Molecules ◽  
Markers Of Inflammation ◽  
Remission Phase

Abstract Background Experimental studies have shown that cell adhesion molecules contribute to the constant induction of pro-inflammatory cytokines (interleukin (6, 8, 10), necrosis factor of tumor-α), providing the chronicity of immune-mediated inflammation at ulcerative colitis (UC). Determination of the importance of molecules of integrin adhesion (sVCAM-1) and mucosal adressin (sMAdCAM-1) for evaluating the effectiveness of treatment of patients with UC. Methods 119 patients with UC were examined: 17 (14.3%) with proctitis, 44 (37%) with left-sided localization, 58 (48.7%) with the total form. The comparison group consisted of 20 healthy volunteers. Determination of serum sVCAM and sMAdCAM was carried out by quantitative enzyme-linked immunosorbent assay (ELISA) based on a system for multiplex analysis using flow fluorimetry — Luminex MAGPIX (USA), ICAM-1 kit (Cusabio, USA). The indicators were assessed before the start of the basic therapy course, in accordance with national recommendations, and 12 weeks after its completion. Results In patients with left-sided and total UC, a 3.2 and 4.7-fold increase in sVCAM expression and a 2.8, 3.6-fold increase in sMAdCAM expression was recorded, averaging: 386.6 + 21.2 ng/ml, 623.4 + 11.1 ng/ml; 116.5 + 13.6 ng/ml, 193.8 + 15.2 ng/ml, respectively (p &lt;0.001). In the group with rectal lesions, there was a moderate increase in the expression of adhesion molecules: 157.1 + 11.3 ng/ml, 84.5 + 18.8 ng/ml, respectively (p&lt;0.07). Against the background of a 12-week treatment course, clinical and endoscopic remission was recorded in 84 (70.6%) patients. In the groups of patients with left-sided and total UC in the drug remission phase, there was a decrease in the expression of sVCAM (194.6 + 9.2 ng/ml, 236.7 + 14.1 ng/ml) and sMAdCAM (72.4 + 8.1 ng/ml, 98.2 + 9.7 ng/ml), respectively (p &lt;0.02). In cases with UC activity, increased levels of adhesion molecules persisted. Conclusion The soluble adhesion molecules of sVCAM and sMAdCAM are modern markers of inflammation that can be used for assessing the effectiveness of course therapy of UC.

scholarly journals Multimarker method in the study of laboratory predictors of vascular wall elasticity as the basis for the development of a personalized approach to the treatment of socially significant diseases

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
T Petelina ◽  
K Avdeeva ◽  
N Musikhina ◽  
L Gapon ◽  
S Bykova ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Postmenopausal Women ◽  
Ldl Cholesterol ◽  
Blood Pressure Monitoring ◽  
Vascular Inflammation ◽  
Fold Increase ◽  
Endothelin 1 ◽  
T Score ◽  
Markers Of Inflammation

Abstract Funding Acknowledgements Type of funding sources: None. Aim To investigate the role of markers of vascular inflammation, vitamin D, parathyroid hormone as predictors of increased pulse-wave velocity (PWV) and degenerative bone changes in postmenopausal women with arterial hypertension (AH). Methods 164 females were examined. Gr.1 included 42 healthy individuals, Gr.2 - 58 patients with AH and Gr.3 - 64 postmenopausal women with AH and osteoporosis. Parameters of blood pressure monitoring; PWV, osteodensitometry (T-Score); inflammatory markers: hsCRP, TNFα, homocysteine, IL-1β, 6, 8, endothelin-1; lipid profile parameters; sex and parathyroid hormones, vitamin D  were measured. Results In Gr.3 excess levels of PWV, hsCRP, homocysteine, IL8, total cholesterol, LDL cholesterol, endothelin-1 and parathyroid hormone was detected with decrease in the level of sex hormones and vitamin D. Besides, negative correlations of T-Score with age, PWV, duration of menopause, IL-6, hsCRP were registered; positive correlations between PWV with IL6, LDL cholesterol, hsCRP, endothelin-1, DBP variability were found. The logistic regression method revealed the main markers that affect increase of PWV, such as hsCRP and endothelin-1.Rise of each marker by unit of measurement leads to increase in PWV by 1.3 times and 2.4%, respectively. In Gr.2 increase in PWV level of more than 12.05 m/s was associated with 3.8-fold increase in the risk of osteoporosis. In Gr.3 increase in PWV level on 1 m/s was associated with 6 fold increase in the risk of osteoporosis. Conclusions Elevated levels of PWV are associated with markers of inflammation, levels of parathyroid hormone, vitamin D, T-Score and may be part of the pathogenesis of the cardiovascular continuum in postmenopausal women, which will require an individual approach to the treatment of AH with comorbid metabolic disorders.

Abstract TMP90: Frequency and Risk Factors for Early Neurological Deterioration Among Hyperacute Cerebral Ischemia Patients Treated With and Without Thrombolysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Christa D Brown ◽  
Gilda Avila-Rinek ◽  
Nerses Sanossian ◽  
Sidney Starkman ◽  
Scott Hamilton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cerebral Ischemia ◽  
Fold Increase ◽  
Information Criteria ◽  
Neurological Deterioration ◽  
Stroke Severity ◽  
Acute Cerebral Ischemia ◽  
Early Neurological Deterioration ◽  
Prior Stroke ◽  
Iv Tpa

Background: Early neurological deterioration (END) is a feared complication of acute cerebral ischemia. However, estimates of END frequency vary widely, rates have not been systematically examined in hyperacute patients presenting within the first 2h of onset, nor separately in patients treated with and without thrombolysis, and risk factors for END have not been well delineated. Methods: We analyzed patients with a final diagnosis of acute cerebral ischemia in the NIH FAST-MAG Phase 3 multicenter clinical trial. END was defined as worsening post-admission by ≥ 4 NIHSS points up to Day 4. We separately analyzed patients who did and did not receive IV tPA. Results: Among 1245 acute cerebral ischemia patients transported by EMS to 55 stroke centers, time from last known well (LKW) to ED arrival was median 59 mins (IQR 80-46), and 36.1% received IV tPA. Overall, 211 (16.9%) experienced END by Day 4, with a greater proportion of END in tPA than non-tPA patients (21.2% vs 14.5%, p=0.003). In multivariate analysis, from 26 candidate variables, among tPA recipients, independent predictors of END were: age (OR 1.03/year, 95%CI 1.01-1.05), diastolic BP (OR 1.01/mm Hg, 95%CI 1.00-1.03), prior stroke (OR 1.65, 95%CI 0.98-2.77), glucose (OR 11.06/10 fold increase, 95%CI 1.90-64.44), and worse ASPECTS score (OR 0.85/point, 95%CI 0.78-0.92). Among non-tPA recipients, independent predictors of END were: more severe NIHSS (OR 1.08/point, 95%CI 1.05-1.11), glucose (OR 8.88/10 fold increase, 95%CI 1.83-43.12), and h/o hypertension (OR 2.62/mm Hg, 95%CI 1.25-5.48), with Akaike information criteria identifying SBP, shorter LKW-to-ED time, and absence of anticoagulant agents as additional contributors. C statistics for these models were 0.68 for tPA patients and 0.73 for non-tPA patients. Conclusions: Among hyperacute cerebral ischemia patients, END occurs in 1 in 5 who receive tPA, and 1 in 7 who do not receive tPA. Greater initial stroke severity (on neurologic exam or imaging), higher glucose, and hypertension increase risk of END for both lytic and non-lytic patients, with older age and prior stroke additionally increasing END risk with tPA. Models based on these risk factors show fair to good performance identifying patients who will experience END after hospital admission.

Abstract TP20: Longer Procedural Times Are Independently Associated with Symptomatic Intracranial Hemorrhage in Large Vessels Occlusion Stroke Patients Undergoing Thrombectomy

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Omar Kass-Hout ◽  
Tareq Kass-Hout ◽  
Michael R. Frankel ◽  
Fadi Nahab ◽  
Samir R. Belagaje ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Infarct Volume ◽  
P Value ◽  
Procedure Time ◽  
Entire Cohort ◽  
Radiographic Outcomes ◽  
Academic Center ◽  
Procedural Time ◽  
Symptomatic Intracranial Hemorrhage

Background and Purpose: Time to reperfusion is an essential factor in determination of outcomes in (AIS). We sought to establish the effect of the procedural time on the clinical and radiographic outcomes of AIS patients undergoing intra-arterial therapy. Methods: Retrospective review of a prospectively collected database of endovascularly treated large vessel AIS in a large academic center. Data from all consecutive patients who underwent mechanical thrombectomy from September 2010 to July 2012 were analyzed. The variable of interest was procedural time (defined as time from groin puncture to end of procedure). Outcome measures included the rates of symptomatic intracebral hemorrhage (sICH, defined as any parenchymal hematoma e.g. PH-1/PH-2), final infarct volume, 90-day mortality, and independent functional outcomes (modified Rankin Scale, mRS 0-2) at 90 days. Results: The entire cohort included 242 patients with a mean age of 65.5+/- 14.2 and median baseline NIHSS 20. Of the patients 49.38% were females. The median ASPECTS score was 8. The mean procedure time was significantly shorter in patients with good outcome (86.73 vs. 73.13 respectively, P-value: 0.0228). However, after controlling for ASPECTS score, type of retrieval device, TICI score, volume of infarct, interval from symptoms onset to puncture, and co-morbidities, this association did not prove to be significant (P-value = 0.7101). Patients with SICH had significantly higher mean procedure time than patients without SICH (79.65 vs. 104.5 respectively; P-value: 0.0319) which remained significant when controlling to the previous factors (OR = 0.974 with a 95 % CI of (0.957, 0.991). There was no correlation between the volume of infarction and the procedure time (r = 0.10996, P-value: 0.0984). There was no association between procedure time and 90-day mortality (77.8 vs. 88.2 minutes in survivals vs. deaths respectively; P-value: 0.0958). Conclusion: Our data support an association between the risk of SICH and a longer procedure time while no definite association between procedural times and the final infarction volume or long-term functional outcomes was found after adjustment for multiple imbalances.

Abstract 11511: Genetic Variation in Retinal Vascular Patterning Predicts Variation in Pial Collateral Extent and Infarct Volume After Middle Cerebral Artery Occlusion

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pranay Prabhakar ◽  
Hua Zhang ◽  
De Chen ◽  
Stephen Lockett ◽  
James E Faber
Keyword(s):  
Genetic Variation ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Genetic Background ◽  
Infarct Volume ◽  
Indirect Evidence ◽  
Artery Occlusion ◽  
Stroke Severity ◽  
Cerebral Artery Occlusion

Introduction: The presence of a native (pre-existing) collateral circulation in tissues lessens injury in stroke and other occlusive diseases. However, differences in genetic background are accompanied by wide variation in the number and diameter (extent) of native collaterals in mice, resulting in large variation in protection. Indirect evidence suggests a similar wide variation also exists in humans. However, methods of measurement in humans are indirect, invasive and not widely available. Hypothesis: We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal circulation, and if these differences predict differences in collateral extent and, in turn, differences in severity of ischemic stroke. Methods: Patterning metrics were obtained for the retinal arterial trees of 10 mouse strains (n=8 per strain) that differ widely in collateral extent in brain and other tissues. We also obtained pial collateral number and diameter, and infarct volume 24h after permanent middle cerebral artery occlusion. Forward- and reverse-stepwise multivariate regression analysis was conducted and model performance assessed using K-fold cross-validation. Results: Twenty-one metrics varied significantly with genetic strain (p<0.01). Ten metrics (eg, vessel caliber, bifurcation angle, lacunarity, optimality, branch length) strongly predicted collateral number and diameter across 7 regression models. The best models closely predicted (p<0.0001) collateral number (K-fold R 2 =0.83-0.98), diameter (0.73-0.88) and infarct volume (0.85-0.87). Conclusions: Differences in retinal tree patterning are specified by genetic background and closely predict genetic variation in pial collateral extent and, in turn, stroke severity. If these findings can be confirmed in humans, and given that genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could be developed as a biomarker for collateral extent in brain and other tissues. This could aid prediction of the risk-severity of tissue injury in occlusive disease as well as stratification of patients for treatment options and enrollment in clinical studies.

scholarly journals Pathogenetic significance of endothelial dysfunction in formation of vascular wall hypertonia in local cold trauma

2020 ◽  
pp. 54-61
Author(s):  
М.И. Михайличенко ◽  
К.Г. Шаповалов ◽  
В.А. Мудров ◽  
С.А. Фигурский ◽  
Р.С. Емельянов
Keyword(s):  
Control Level ◽  
Lower Extremities ◽  
Fold Increase ◽  
Vascular Wall ◽  
Cold Injury ◽  
Circulating Endothelial Cells ◽  
Control Group ◽  
Blood Levels ◽  
Control Value ◽  
Local Cold Injury

Актуальность. В структуре общего травматизма местная холодовая травма имеет большой удельный вес. Выявление новых маркеров криоповреждения способствует более ранней диагностике глубины поражений тканей при обморожении, созданию новых подходов к хирургическому лечению и ускоренной реабилитации пострадавших. Цель исследования - изучение в динамике содержания оксида азота, асимметричного диметиларгинина и циркулирующих эндотелиальных клеток в сыворотке крови у пациентов с местной холодовой травмой. Методика. В исследование включено 80 пациентов с обморожениями нижних конечностей III-IV степени в позднем реактивном периоде и периоде гранулирования и эпителизации. Использован мультиплексный анализ сыворотки крови набором реагентов фирмы Biomedical (США), методом Hladovec (1978) и методом П.П. Голикова (2004) соответвенно. Результаты. У пациентов с криотравмой во всех исследуемых группах установлено снижение уровня оксида азота относительно контроля. У пострадавших с местной холодовой травмой на 5-е сут отмечено значительное снижение в крови уровня асимметричного диметиларгинина. на 30-е сут с момента криоповреждения уровень асимметричного диметиларгинина не отличался от показателей контрольной группы. При обморожении дистальных сегментов стоп концентрация асимметричного диметиларгинина в крови не менялась относительно контроля. У пациентов с тяжелыми обморожениями нижних конечностей уровень асимметричного диметиларгинина в крови снижался в 3,6 раза. У пациентов с местной холодовой травмой на 5-е сут установлено увеличение в крови уровня циркулирующих эндотелиальных клеток в 5,2 раза, на 30-е сут с момента криоповреждения уровень циркулирующих эндотелиальных клеток снижался, но, по-прежнему, превышал контрольные значения. У пострадавших с обморожением дистальных сегментов стоп содержание в крови циркулирующих эндотелиальных клеток увеличилось в 2,7 раза, с поражением проксимальных сегментов нижних конечностей - в 6,7 раза относительно здоровых добровольцев. У пациентов с наиболее тяжелыми обморожениями нижних конечностей уровень циркулирующих эндотелиальных клеток в крови повышался в 9 раз. The relevance of local cold injury remains high. In the structure of general injury prevalence, proportion of freeze burns is great. Identification of new markers of cold injury will help earlier determination of tissue lesion depth, development of new approaches in the surgical treatment of deep freeze burns of extremities, and promote rehabilitation of patients. The aim of this study was to elucidate the dynamics of the serum content of nitric oxide (NO), asymmetric dimethylarginine (ADMA), and circulating endothelial cells (CEC) in patients with local cold injury. Methods. The study included 80 patients with III-IV degree frostbite of the lower extremities in the late reactive period and the period of granulation and epithelization. Multiplex analyses of blood serum were performed with Biomedical (USA) reagent kits, according to methods by Hladovec (1978) and Golikov (2004). Results. In all groups of patients with frostbite, NO level was decreased compared to the control. Patients with local cold trauma displayed significant decreases in blood levels of ADMA on day 5; on day 30 after the cold trauma, the ADMA level did not differ from the control group. In patients with frostbite of the distal foot segments, the blood concentration of ADMA did not change from the control level. In patients with the most severe frostbite of the lower extremities, serum ADMA decreased 3.6 times. Patients with local cold trauma had a 5.2-fold increase in the blood level of CEC on day 5. On day 30 after the freeze burn, the amount of CEC was decreased but still remained above the control value. In patients with frostbite of the distal foot segments, the content of CEC increased 2.7 times compared to the control. In patients with lesions of more proximal segments of the lower extremities, the CEC index was increased 6.7 times compared to healthy volunteers. In patients with the most severe frostbite of the lower extremities, the blood content of CEC was 9 times increased.

Abstract 4579: Endogenous Brain Natriuretic Peptide (BNP) Protects Against Apoptosis of Ischemic Human Astrocytes in an Autocrine Fashion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chisato Katoh ◽  
Hirofumi Tomita ◽  
Norifumi Metoki ◽  
Genta Saitoh ◽  
Tomohiro Osanai ◽  
...  
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Early Stage ◽  
Infarct Volume ◽  
Fold Increase ◽  
Brain Diseases ◽  
Loss Of Function ◽  
Human Astrocytes ◽  
Apoptotic Effect ◽  
And Function

The plasma brain natriuretic peptide (BNP) level is increased in the acute phase of human stroke, but its source and function are unclear. Recently, we showed that the BNP level was higher in atherothrombotic cerebral infarction (69.1±9.4 pg/ml) than in control subjects (31.1±5.4 pg/ml), and that the BNP level in ischemic stroke was positively correlated with the NIH Stroke Scale (r=0.41, p<0.05) and infarct volume (r=0.34, p<0.05). Astrocytes provide metabolic and trophic support to neurons and modulate synaptic activities. At the early stage of brain ischemia, astrocytes are swollen, and their damage may compromise postischemic neuronal survival. We tested the hypothesis that human astrocytes produce BNP under hypoxia, and this endogenous BNP protects against apoptosis in an autocrine fashion. The human astrocyte cell line, U373MG, was exposed to hypoxia (O 2 ≤1%) for 24 hours. The ratio of BNP to GAPDH mRNA was increased by 7.7±.0 fold after 12-hour hypoxia and further increased by 8.6±1.6 fold after 24-hour hypoxia compared with that in 3-hour normoxia (both, p<0.01). The protein expression assessed by Western blot was increased by 2.0±0.4 fold at 24 hours (n=5, p<0.05). Tyrosine phosphorylation of c-Src was observed by 2.0±0.2-fold increase at 30 minutes. These responses to hypoxia were all blocked by pretreatment with PP1 at 50μM, an inhibitor of c-Src. Apoptosis was measured by detecting caspase activation by flow cytometry, and it was increased by 2.5±0.1 fold after 24-hour hypoxia compared with that in normoxia. To investigate the role of up-regulated BNP in apoptosis, we performed the loss of function test by transfecting a specific siRNA for NPPB that suppressed BNP by more than 80%. The activity of caspases in the BNP knockdown cells was increased by 3.2±0.2 fold after 24-hour hypoxia compared with that in normoxia (n=5, p<0.001), and it was greater than that in the cells transfected with non-targeting siRNA. These results indicate that hypoxia increases BNP gene expression through the c-Src-dependent signaling cascade in the human astrocytes. Endogenous BNP shows brain protection via the anti-apoptotic effect. BNP may be useful in the treatment of ischemic brain diseases.

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