scholarly journals Anti-VEGF therapy prevents Müller intracellular edema by decreasing VEGF-A in diabetic retinopathy

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Tianqin Wang ◽  
Chaoyang Zhang ◽  
Hai Xie ◽  
Mengmeng Jiang ◽  
Haibin Tian ◽  
...  
Keyword(s):  
Intracellular Sodium ◽  
Diabetic Rat ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Sodium Potassium ◽  
Intracellular Potassium ◽  
Sprague Dawley Rats ◽  
Endothelial Growth Factor ◽  
Inwardly Rectifying

Abstract Background Although vascular endothelial growth factor A (VEGF-A) is known to play a key role in causing retinal edema, whether and how VEGF-A induces intracellular edema in the retina still remains unclear. Methods Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin. Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset. rMC-1 cells (rat Müller cell line) were treated with glyoxal for 24 h with or without ranibizumab. The expression levels of inwardly rectifying K+ channel 4.1 (Kir4.1), aquaporin 4 (AQP4), Dystrophin 71 (Dp71), VEGF-A, glutamine synthetase (GS) and sodium-potassium-ATPase (Na+-K+-ATPase) were examined using Western blot. VEGF-A in the supernatant of the cell culture was detected with ELISA. The intracellular potassium and sodium levels were detected with specific indicators. Results Compared with normal control, protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas, which were prevented by ranibizumab. The above changes were recapitulated in vitro. Similarly, the intracellular potassium level in glyoxal-treated rMC-1 cells was increased, while the intracellular sodium level and Na+-K+-ATPase protein level remained unchanged, compared with control. However, ranibizumab treatment decreased intracellular sodium, but not potassium. Conclusion Ranibizumab protected Müller cells from diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A. It also caused a reduction in intracellular osmotic pressure.

Sevoflurane Preconditioning Attenuates the Fall in Adenosine Triphosphate Levels, but Does Not Alter the Changes in Sodium and Potassium Levels during Hypoxia in Rat Hippocampal Slices

2013 ◽  
Vol 119 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Brandon R. Esenther ◽  
Zhijun Ge ◽  
Fanli Meng ◽  
James E. Cottrell ◽  
Ira S. Kass
Keyword(s):  
Adenosine Triphosphate ◽  
Hippocampal Slices ◽  
Intracellular Sodium ◽  
Sprague Dawley ◽  
Sodium Potassium ◽  
Atp Levels ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Sevoflurane Preconditioning ◽  
Sodium And Potassium

Abstract Background: Sevoflurane preconditioning improves recovery after hypoxia. Sevoflurane administered before and during hypoxia improved recovery and attenuated the changes in intracellular sodium, potassium, and adenosine triphosphate (ATP) levels during hypoxia. In this study, the authors examine the effects of sevoflurane applied only before hypoxia on sodium, potassium, and ATP. Methods: Hippocampal slices from adult male Sprague–Dawley rats were pretreated with 4% sevoflurane, washed, and then subjected to hypoxia (n ≥ 8 animals/group). The cornus ammonis 1 regions of the hippocampal slices were micro-dissected and sodium, potassium, and ATP concentrations measured. Results: Pretreatment with sevoflurane for 15 or 60 min did not attenuate the increase in intracellular sodium or the decrease in intracellular potassium during hypoxia. After 60 min of preconditioning and 5 min of hypoxia, sodium increased 57% (vs. nonpreconditioned hypoxia 54% increase) and potassium decreased 31% (vs. 26%). These changes were not statistically significant versus untreated hypoxia. The 60-min sevoflurane preconditioning group had statistically significant higher ATP levels at 5 min of hypoxia (3.8 nmol/mg dry wt.) when compared to untreated hypoxic tissue (2.1 nmol/mg). There was no significant difference in ATP levels between the sevoflurane preconditioned and the untreated tissue before hypoxia (8.9 vs. 8.5 nmoles/mg, respectively). Conclusion: Preconditioning with sevoflurane for 60 min before hypoxia does not alter changes in intracellular sodium and potassium during hypoxia but does attenuate the fall in intracellular ATP levels during hypoxia. Thus, there are differences between anesthetic preconditioning and when anesthetics are present before and during hypoxia.

DITPA stimulates bFGF, VEGF, angiopoietin, and Tie-2 and facilitates coronary arteriolar growth

2003 ◽  
Vol 284 (2) ◽  
pp. H613-H618 ◽  
Author(s):  
Xinguo Wang ◽  
Wei Zheng ◽  
Lance P. Christensen ◽  
Robert J. Tomanek
Keyword(s):  
Growth Factor ◽  
Relative Number ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Sprague Dawley ◽  
Capillary Length ◽  
Sprague Dawley Rats ◽  
Hormone Analog ◽  
Endothelial Growth Factor ◽  
Angiopoietin 1

Previous studies from our laboratory and those of others have shown thyroxine to be a stimulator of coronary microvascular growth. The present study tested the hypothesis that 3,5-diiodothyropropionic acid (DITPA), a thyroid hormone analog with inotropic but not chronotopic characteristics, is angiogenic in the nonischemic heart. Daily injections (3.75 mg/kg sc) of DITPA to Sprague-Dawley rats affected protein increases in vascular endothelial growth factor (VEGF)164, VEGF188, basic fibroblast growth factor (bFGF) (FGF-2), angiopoietin-1, and Tie-2 during the first few days of treatment. After 3 wk of treatment, arteriolar length density and the relative number of terminal arterioles (<10 μm diameter) increased in the left ventricle as determined by image analysis of perfuse-fixed hearts. These findings occurred in hearts that did not undergo changes in mass nor in increases in capillary length density. We conclude that DITPA, which is known to improve ventricular function after infarction, is angiogenic in normal nonischemic hearts.

Endothelial molecular changes in a rodent model of arteriovenous malformation

2008 ◽  
Vol 109 (6) ◽  
pp. 1165-1172 ◽  
Author(s):  
Athula Karunanyaka ◽  
Jian Tu ◽  
Amy Watling ◽  
Kingsley P. Storer ◽  
Apsara Windsor ◽  
...  
Keyword(s):  
Animal Model ◽  
Arteriovenous Malformation ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Molecular Changes ◽  
Arteriovenous Fistulas ◽  
Sprague Dawley Rats ◽  
Fresh Frozen ◽  
Von Willebrand ◽  
Endothelial Growth Factor

Object The cellular and molecular processes underlying arteriovenous malformation (AVM) development and response to radiosurgery are largely unknown. An animal model mimicking the molecular properties of AVMs is required to examine these processses. This study was performed to determine whether the endothelial molecular changes in an animal model of arteriovenous fistula (AVF) are similar to those in human AVMs. Methods Arteriovenous fistulas were created in 18 Sprague–Dawley rats by end-to-side anastomosis of the left jugular vein to the common carotid artery creating a model “nidus” of arterialized branching veins that coalesce into a “draining vein” (sigmoid sinus). Six control animals underwent sham operations. Results After 1 or 3 days, or 1, 3, 6, or 12 weeks, fresh-frozen sections of the fistula, nidus vessels, and contralateral vessels were studied immunohistochemically for thrombomodulin, von Willebrand factor, E-selectin, P-selectin, and vascular endothelial growth factor. Conclusions The AVF model has a “nidus” with endothelial molecular changes similar to those observed in human AVMs, supporting its use as a model for studying the effects of radiosurgery on AVMs.

scholarly journals Progesterone Attenuates Hemorrhagic Transformation after Delayed tPA Treatment in an Experimental Model of Stroke in Rats: Involvement of the VEGF–MMP Pathway

2013 ◽  
Vol 34 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Soonmi Won ◽  
Jin Hwan Lee ◽  
Bushra Wali ◽  
Donald G Stein ◽  
Iqbal Sayeed
Keyword(s):  
Time Window ◽  
Culture Media ◽  
Hemorrhagic Transformation ◽  
Artery Occlusion ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Bbb Permeability ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for acute stroke, but its use remains limited. Progesterone (PROG) has shown neuroprotection in ischemia, but before clinical testing, we must determine how it affects hemorrhagic transformation in tPA-treated ischemic rats. Male Sprague–Dawley rats underwent middle cerebral artery occlusion with reperfusion at 4.5 hours and tPA treatment at 4.5 hours, or PROG treatment intraperitoneally at 2 hours followed by subcutaneous injection at 6 hours post occlusion. Rats were killed at 24 hours and brains evaluated for cerebral hemorrhage, swelling, blood–brain barrier (BBB) permeability, and levels of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor level (VEGF), and tight junction (TJ) proteins. We also evaluated PROG's efficacy in preventing tPA-induced impairment of transendothelial electrical resistance (TEER) and TJ proteins under hypoxia/reoxygenation in the endothelial cells. Delayed tPA treatment induced significant hemorrhagic conversion and brain swelling. Treatment with PROG plus tPA ameliorated hemorrhage, hemispheric swelling, BBB permeability, MMP-9 induction, and VEGF levels compared with controls. Progesterone treatment significantly prevented tPA-induced decrease in TEER and expression of occludin and claudin-5, and attenuated VEGF levels in culture media subjected to hypoxia. The study concluded that PROG may extend the time window for tPA administration in ischemic stroke and reduce hemorrhagic conversion.

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