scholarly journals Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shusaku Maeda ◽  
Shigeru Miyagawa ◽  
Takuji Kawamura ◽  
Takashi Shibuya ◽  
Kenichi Watanabe ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Tissue Perfusion ◽  
Human Mesenchymal Stem Cell ◽  
Capillary Density ◽  
Adductor Muscle ◽  
Notch Signaling Pathway ◽  
Hindlimb Ischemia ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Whole Transcriptome Analysis

AbstractNotch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague–Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 105 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter  > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.

Exercise training and its effects with renal hypertensive rats

1985 ◽  
Vol 59 (5) ◽  
pp. 1410-1415 ◽  
Author(s):  
K. D. Marcus ◽  
C. M. Tipton
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Capillary Density ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vo2 Max ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Resting Blood Pressure ◽  
Renal Hypertensive Rats

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120–140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150–170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190–230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50–70% of their VO2 max values for 8–12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12–15%) and muscle cytochrome-c oxidase activities (33–78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20–30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.

scholarly journals Effect of diaspirin cross-linked hemoglobin on normal and postischemic microcirculation of the rat pancreas

1999 ◽  
Vol 276 (6) ◽  
pp. G1507-G1514 ◽  
Author(s):  
Ernst von Dobschuetz ◽  
Tomas Hoffmann ◽  
Clemens Engelschalk ◽  
Konrad Messmer
Keyword(s):  
Detrimental Effect ◽  
Oxygen Carrier ◽  
Capillary Density ◽  
Control Group ◽  
Leukocyte Adherence ◽  
Sprague Dawley ◽  
Rat Pancreas ◽  
Sprague Dawley Rats ◽  
Pancreatic Ischemia ◽  
Complete Restoration

Microcirculatory alterations with reduced nutritive supply to the pancreas could be the cause of hyperamylasemia, which occurs in some patients receiving the vasoactive oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in clinical studies. Therefore, the effects of DCLHb on rat pancreas microcirculation were evaluated. Anesthetized Sprague-Dawley rats received one of the following treatments during baseline conditions ( n = 7 rats/group): 10% hydroxyethyl starch (HAES) (0.4 ml/kg), DCLHb (400 mg/kg), or DCLHb (1,400 mg/kg). After 1 h of complete, reversible pancreatic ischemia, other animals received 10% HAES (0.4 ml/kg) or DCLHb (400 mg/kg) during the onset of reperfusion. The number of red blood cell-perfused capillaries (functional capillary density, FCD) and the level of leukocyte adherence in postcapillary venules in the pancreas were assessed by means of intravital microscopy during 2 h after treatment. In the nonischemic groups, FCD was 18% greater after DCLHb (1,400 mg/kg) than after 10% HAES treatment without any increase in leukocyte adherence. In the inschemia-reperfusion (I/R) 10% HAES group, FCD was significantly ( P < 0.05) lowered, leukocyte adherence enhanced, and mean arterial pressure (MAP) reduced by 31% compared with nonischemic animals. DCLHb treatment in the I/R group resulted in a slight increase in FCD, a significant ( P < 0.05) reduction of leukocyte adherence, and a complete restoration of MAP compared with the animals of the I/R control group. Thus our data provide no evidence for a detrimental effect on the pancreatic microcirculation or an enhanced risk of postischemic pancreatitis by DCLHb.

scholarly journals Dynamic Evaluation of Notch Signaling-Mediated Angiogenesis in Ischemic Rats Using Magnetic Resonance Imaging

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Jia-qi Tian ◽  
Jia-jun Zheng ◽  
Xiao-zhu Hao ◽  
Le-kang Yin ◽  
Xiao-xue Zhang ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Notch Signaling ◽  
Butyl Ester ◽  
Notch Signaling Pathway ◽  
Control Group ◽  
Vascular Density ◽  
Resonance Imaging ◽  
Sprague Dawley ◽  
Mri Scans

Objective. The Notch signaling pathway is involved in angiogenesis induced by brain ischemia and can be efficiently inhibited by the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). The aim of the present study was to noninvasively investigate the effect of DAPT treatment on angiogenesis in brain repair after stroke using magnetic resonance imaging (MRI). Methods. Sprague-Dawley rats (n=40) were subjected to 90 minutes of transient middle cerebral artery (MCA) occlusion and treated with PBS (n=20) or DAPT (n=20) at 72 hours after the onset of ischemia. MRI measurements including T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and cerebral blood flow (CBF) were performed at 24 hours after reperfusion and weekly up to 4 weeks using a 3-Tesla system. Histological measurements were obtained at each time point after MRI scans. Results. SWI showed that DAPT treatment significantly enhanced angiogenesis in the ischemic boundary zone (IBZ) with respect to the control group, with local CBF in the angiogenic area elevated, along with increases in vascular density confirmed by histology. Conclusion. Treatment of ischemic stroke with DAPT significantly augments angiogenesis, which promotes poststroke brain remodeling by elevating CBF level, and these processes can be dynamically monitored and evaluated by MRI.

scholarly journals Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

2009 ◽  
Vol 201 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Marina Komrakova ◽  
Carsten Werner ◽  
Michael Wicke ◽  
Ba Tiep Nguyen ◽  
Stephan Sehmisch ◽  
...  
Keyword(s):  
Gastrocnemius Muscle ◽  
Cell Metabolism ◽  
Capillary Density ◽  
Mitochondrial Activity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Level Versus ◽  
Morphological Differences ◽  
Tibia Osteotomy ◽  
Estradiol 17Β

The effect of daidzein (D), 4-methylbenzylidene camphor (4-MBC) or estradiol-17β-benzoate (E2) on muscle of osteoporotic rats during fracture healing was studied. After performing a metaphyseal tibia osteotomy in 96 osteoporotic 5-month-old female Sprague–Dawley rats, they received daily 50 mg D, 200 mg 4-MBC or 0.4 mg E2 per kg body weight, or soy free (SF) diet up to 36 and 72 days. Mitochondrial activity, fiber area, and capillary density were analyzed in M. gastrocnemius. Osseous callus bridging of fracture was observed in half of the rats after 36 days. By day 72, fracture was healed in most of the animals. State 3 mitochondrial respiration significantly enhanced in E2, 4-MBC and D groups versus SF after 36 days (30, 32 and 32 vs 23 pmol O2/s per mg). It declined after 72 days, however, in E2 group it was still at a higher level versus SF (25, 23 and 21 vs 20 pmol O2/s per mg). Size of fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers, capillary density did not differ significantly between the groups, however, at day 36 an increase in D and 4-MBC groups was detectable. FOG diameter was 64, 66, 68, and 58 μm and FG diameter was 88, 98, 95, and 89 μm in SF, D, 4-MBC, and E2 groups. The ratio of capillaries to muscle fiber was 1.1, 1.4, 1.3, and 1.1 in SF, D, 4-MBC and E2 groups by day 36. D and 4-MBC react similar to estrogen thereby improving oxidative cell metabolism in severe osteoporotic rats. The level of mitochondrial activity was higher, though no significant morphological differences could be shown.

Effects of exercising rats during pregnancy

1980 ◽  
Vol 48 (1) ◽  
pp. 34-40 ◽  
Author(s):  
N. C. Wilson ◽  
C. V. Gisolfi
Keyword(s):  
Blood Flow ◽  
Left Ventricle ◽  
Maximal Oxygen Consumption ◽  
Capillary Density ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Response To Stress ◽  
Maternal Exercise ◽  
The Right ◽  
Exercise During Pregnancy

To determine the effects of exercise during pregnancy on the cardiovascular system of their progeny, female Sprague-Dawley rats were assigned to one of four groups: 1) trained-nontrained (T-NT) animals who ran for 7 wk at 35 m/min before but not during pregnancy; 2) T-T animals who ran at 35 m/min before and at 32 m/min during pregnancy; 3) control (C) animals who did not exercise; and 4) NT-T animals who only ran (16 m/min) during pregnancy. Significant increases in skeletal muscle cytochrome found between exercised (NT-T, T-T) and nonexercised (C, T-NT) mothers; C animals had significantly lower maximal oxygen consumption (VO2max) values than T-T animals at the end of pregnancy. Offspring mortality was greater (P less than 0.05) in the T-T compared with the C group during the 28 days following birth. Maternal exercise had no significant influence on VO2max in the offspring or on myocardial blood flow when these animals were ventilated with either hypoxic (10% O2) or normoxic (21% O2) gases. Right ventricular fiber areas were smaller (P less than 0.05) in T-T and NT-T animals compared with the T-NT group; no significant changes were observed in the left ventricle. Capillary density and fiber-to-capillary ratios were not different in either the right or left ventricle. These results indicate that mild or heavy exercise does not influence VO2max, coronary blood flow in response to stress, or myocardial structure in the male offspring of rats trained during pregnancy.

Skeletal muscle response to spaceflight, whole body suspension, and recovery in rats

1990 ◽  
Vol 69 (6) ◽  
pp. 2248-2253 ◽  
Author(s):  
X. J. Musacchia ◽  
J. M. Steffen ◽  
R. D. Fell ◽  
M. J. Dombrowski
Keyword(s):  
Muscle Mass ◽  
Muscle Metabolism ◽  
Capillary Density ◽  
Whole Body ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Muscle Plasticity ◽  
Sprague Dawley Rats ◽  
Muscle Mass Loss ◽  
Fast Twitch

Comparisons of soleus and extensor digitorum longus (EDL) muscles from male Sprague-Dawley rats (350-400 g) after 7 days of weightlessness, 7 and 14 days of whole body suspension (WBS), and 7 days of recovery from WBS and from vivarium controls were made. Muscle mass loss of approximately 30% was observed in soleus after 7 and 14 days of WBS. Measurement of slow- and fast-twitch fibers showed significant alterations. Reductions in cross-sectional areas and increases in fiber densities in soleus after spaceflight and WBS were related to previous findings of muscle atrophy during unloading. Capillary density also showed a marked increase with unloading. Seven days of weightlessness were sufficient to effect a 20 and 15% loss in absolute muscle mass in soleus and EDL, respectively. However, the antigravity soleus was more responsive in terms of cross-sectional area reductions. After 7 days of recovery from WBS, with normal ambulatory loading, the parameters studied showed a reversal to control levels. Muscle plasticity, in terms of fiber and capillary responses, indicated differences in responses in the two types of muscles and further amplified that antigravity posture muscles are highly susceptible to unloading. Studies of recovery from spaceflight for both muscle metabolism and microvascular modifications are further justified.

Abstract 13158: Impact of Enhancing Fetal Lung Vascular and Alveolar Development by Slow-release Novel Synthetic Prostacyclin Agonist for Treatment of Fetal Lung Hypoplasia

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Satoshi Umeda ◽  
Shigeru Miyagawa ◽  
Satsuki Fukushima ◽  
Akima Harada ◽  
Atsuhiro Saito ◽  
...  
Keyword(s):  
Placebo Group ◽  
Slow Release ◽  
Weight Ratio ◽  
Fetal Lung ◽  
Capillary Density ◽  
Maternal Blood ◽  
Lung Hypoplasia ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Medial Wall Thickness

Background: Lung hypoplasia and persistent pulmonary hypertension associated with critical pathologies, such as congenital diaphragmatic hernia (CDH), is the major cause of mortality in the neonates. Although prostaglandins pathway is known to play a pivotal role in the lung development, effectiveness of postnatal treatment by prostaglandin agonists was reported to be suboptimal. We hypothesized that prenatal treatment by ONO-1301SR, slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might promote development of lungs having hypoplasia in the fetal period. Methods: On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to produce a CDH-relating lung hypoplasia model, while normal rats (n=4) received vehicle only. At the same day, either ONO-1301SR or placebo was randomly given to the nitrofen-treated rats (placebo; n=7, ONO; n=5). On E21.5, the normal fetuses, and the fetuses having CDH were analyzed. Results: Prenatal ONO-1301SR administration had no influence on incidence of nitrofen-induced CDH. One-seventh of maternal blood concentration of ONO-1301 was transferred to fetal blood at E21.5, warranting efficient placental permeability of this molecule. Prostacyclin receptor was expressed in pulmonary arterial smooth muscle cells in the fetus. Lung-to-body weight ratio (%) in the ONO group (1.88±0.07) was greater than that in the placebo group (1.60±0.04, p<0.01). Histologically, medial wall thickness in the ONO group was two-third thinner than that in the placebo group (p<0.01). In addition, the number of Ttf-1-positive cells and capillary density were 1.5 times or more greater in the ONO group than that in the placebo group (p<0.05), associated with a greater expression of VEGF and SDF-1 in the ONO group, suggesting enhanced development of the alveolar and capillary network. Conclusions: Prenatal ONO-1301SR administration promoted efficient development of hypoplastic lungs associated with CDH in the nitrofen-induced rat model, indicating potential of this treatment for pathologies having lung hypoplasia.

Effects of PAF on isolated rat airways perfused with blood-free solution

1991 ◽  
Vol 260 (4) ◽  
pp. L260-L267
Author(s):  
N. M. Munoz ◽  
C. F. Kirchhoff ◽  
M. E. Strek ◽  
R. N. Blumenthal ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Platelet Activating Factor ◽  
Tissue Perfusion ◽  
Sprague Dawley ◽  
Response Curves ◽  
Peripheral Airways ◽  
Sprague Dawley Rats ◽  
Lung Resistance ◽  
Prior Administration

We examined the mechanism of constriction and muscarinic augmentation of contraction of airway smooth muscle caused by platelet-activating factor (PAF) in airways from 55 Sprague-Dawley rats perfused through the isolated bronchial circulation (BC) and pulmonary circulation (PC) and isometrically in tissue perfusion chambers. Dose-response curves were generated cumulatively by infusing 10(-10) to 10(-7) mol PAF dissolved in Krebs-Henseleit solution buffer containing 4% bovine serum albumin into the BC or PC. The efficacy of PAF in central airways (BC) was approximately twofold greater in increasing lung resistance (RL) than for more peripheral airways perfused by the PC (P less than 0.05). Tachyphylaxis was demonstrated in both BC and PC for preparations in which a second PAF dose-response curve was generated. Bolus injection of 10(-6) mol of the PAF antagonist, CV-6209, plus 10(-7) mol PAF caused 81% reversal of the maximal BC response. The same dose of CV-6209 reversed the response to PAF in the PC by 99.2%. Initial administration of 10(-6) mol CV-6209 with PAF prevented completely contraction elicited by PAF in the BC and PC. Concentration-response studies also were generated isometrically in tissue perfusion chambers from 64 tracheal smooth muscle strips. Maximal contraction elicited by 10(-6) M PAF was blocked completely with 10(-6) M CV-6209. In separate studies, addition of 10(-6) mol CV-6209 to the BC perfusate caused 93% blockade of the RL response to PAF and 100% inhibition when administered in the PC. Prior administration of PAF caused two- to fourfold augmentation of the contractile response to acetylcholine (ACh) within the same preparation; in the presence of CV-6209, the response to ACh was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

1982 ◽  
Vol 40 ◽  
pp. 216-217
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Microscopic Study ◽  
Pituitary Adenomas ◽  
Wistar Rats ◽  
Microscopic Level ◽  
Sprague Dawley ◽  
Prolactin Cells ◽  
Light Microscopic Level ◽  
Ultrastructural Investigation ◽  
Sprague Dawley Rats ◽  
Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

Early Development of Drug-Induced Hepatic Necrosis

1971 ◽  
Vol 29 ◽  
pp. 576-577
Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser
Keyword(s):  
Early Development ◽  
Hepatic Necrosis ◽  
Screening Tests ◽  
Dense Matrix ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Drug Induced ◽  
Hepatocellular Damage ◽  
Sprague Dawley Rats ◽  
Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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