scholarly journals Mode Switch of Ca2 + Oscillation-Mediated Uterine Peristalsis and Associated Embryo Implantation Impairments in Mouse Adenomyosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingzi Qu ◽  
Ping Lu ◽  
Karl Bellve ◽  
Lawrence M. Lifshitz ◽  
Ronghua ZhuGe
Keyword(s):  
Tissue Injury ◽  
Embryo Implantation ◽  
Peak Frequency ◽  
Mode Switch ◽  
Adult Mice ◽  
Receptor Modulator ◽  
Intracellular Ca ◽  
Injury And Repair ◽  
Uterine Peristalsis

Adenomyosis is a debilitating gynecological disease of the uterus with no medicinal cure. The tissue injury and repair hypothesis for adenomyosis suggests that uterine hyperperistalsis or dysperistalsis plays a pivotal role in establishing adenomyotic lesions. However, specific impairments in uterine peristalsis and the underlying cellular signals for these changes in adenomyosis remain elusive. Here, we report a precision-cut uterine slice preparation that preserves in vivo uterine architecture and generates peristalsis similar to that seen in the whole uterus. We found that uterine peristalsis in neonatal mice at day 14 and adult mice at day 55 presents as bursts with multiple peaks induced by intracellular Ca2+ oscillations. Using a mouse model of adenomyosis induced by tamoxifen, a selective estrogen receptor modulator, we discovered that uterine peristalsis and Ca2+ oscillations from adenomyotic uteri on days 14 and 55 become spikes (single peaks) with smaller amplitudes. The peak frequency of Ca2+ oscillations or peristalsis does not show a difference between control and adenomyotic mice. However, both the estimated force generated by uterine peristalsis and the total Ca2+ raised by Ca2+ oscillations are smaller in uteri from adenomyotic mice. Uteri from adenomyotic mice on day 14, but not on day 55, exhibit hyperresponsiveness to oxytocin. Embryo implantations are decreased in adenomyotic adult mice. Our results reveal a mode switch from bursts to spikes (rather than an increased peak frequency) of uterine Ca2+ oscillations and peristalsis and concurrent hyperresponsiveness to oxytocin in the neonatal stage are two characteristics of adenomyosis. These characteristics may contribute to embryo implantation impairments and decreased fertility in adenomyosis.

A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2153-2161 ◽  
Author(s):  
Ryang Hwa Lee ◽  
Shu Ching Hsu ◽  
James Munoz ◽  
Jin Sup Jung ◽  
Na Rea Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Adult Stem Cells ◽  
Tissue Injury ◽  
Marrow Stromal Cells ◽  
Immunodeficient Mice ◽  
Adult Mice

Controversies have arisen as to whether adult stem cells or progenitor cells from bone marrow can engraft into nonhematopoietic tissues in vivo. To resolve some of the controversies, we developed a highly sensitive polymerase chain reaction-based single nucleotide polymorphism (PCR-SNP) assay for competitive engraftment of mixtures of stem/progenitor cells. We used the assay to follow engraftment in immunodeficient mice of subpopulations of the stem/progenitor cells from human bone marrow referred to as either mesenchymal stem cells or marrow stromal cells (MSCs). The engraftment into adult mice without induced tissue injury was low and variable, but there was preferential engraftment of a subpopulation of rapidly self-renewing MSCs (RS-MSCs) compared with a subpopulation of slowly renewing MSCs (SR-MSCs). After intravenous infusion, there was a tendency for the cells to engraft into the hippocampal region that was previously designated a “vascular niche.” Migration assays suggested that preferential engraftment of RS-MSCs was in part explained by their expression of CXCR4 and CX3R1, the receptors for SDF-1 and fractalkine.

scholarly journals Somatic calcium level reports integrated spiking activity of cerebellar interneurons in vitro and in vivo

2011 ◽  
Vol 106 (4) ◽  
pp. 1793-1805 ◽  
Author(s):  
Romain Franconville ◽  
Gaëlle Revet ◽  
Guadalupe Astorga ◽  
Beat Schwaller ◽  
Isabel Llano
Keyword(s):  
Time Course ◽  
Molecular Layer ◽  
Concentration Data ◽  
Two Photon Microscopy ◽  
Adult Mice ◽  
Intracellular Ca ◽  
The Relationship ◽  
Spiking Activity

We examined the relationship between somatic Ca2+ signals and spiking activity of cerebellar molecular layer interneurons (MLIs) in adult mice. Using two-photon microscopy in conjunction with cell-attached recordings in slices, we show that in tonically firing MLIs loaded with high-affinity Ca2+ probes, Ca2+-dependent fluorescence transients are absent. Spike-triggered averages of fluorescence traces for MLIs spiking at low rates revealed that the fluorescence change associated with an action potential is small (1% of the basal fluorescence). To uncover the relationship between intracellular Ca2+ concentration ([Ca2+]i) and firing rates, spikes were transiently silenced with puffs of the GABAA receptor agonist muscimol. [Ca2+]i relaxed toward basal levels following a single exponential whose amplitude correlated to the preceding spike frequency. The relaxation time constant was slow (2.5 s) and independent of the probe concentration. Data from parvalbumin (PV)−/− animals indicate that PV controls the amplitude and decay time of spike-triggered averages as well as the time course of [Ca2+]i relaxations following spike silencing. The [Ca2+]i signals were sensitive to the L-type Ca2+ channel blocker nimodipine and insensitive to ryanodine. In anesthetized mice, as in slices, fluorescence traces from most MLIs did not show spontaneous transients. They nonetheless responded to muscimol iontophoresis with relaxations similar to those obtained in vitro, suggesting a state of tonic firing with estimated spiking rates ranging from 2 to 30 Hz. Altogether, the [Ca2+]i signal appears to reflect the integral of the spiking activity in MLIs. We propose that the muscimol silencing strategy can be extended to other tonically spiking neurons with similar [Ca2+]i homeostasis.

scholarly journals Spontaneous Calcium Waves in Bergman Glia Increase with Age and Hypoxia and may Reduce Tissue Oxygen

2012 ◽  
Vol 33 (2) ◽  
pp. 161-169 ◽  
Author(s):  
Claus Mathiesen ◽  
Alexey Brazhe ◽  
Kirsten Thomsen ◽  
Martin Lauritzen
Keyword(s):  
Oxygen Tension ◽  
Cerebellar Cortex ◽  
Energy Homeostasis ◽  
Oxygen Metabolism ◽  
Wave Activity ◽  
Blood Oxygen Saturation ◽  
Brain Oxygen ◽  
Adult Mice ◽  
Intracellular Ca

Glial calcium (Ca2+) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca2+ waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O2 tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca2+ activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

1108: Treatment Strategy Improves the in Vivo Stone Comminution Efficiency and Reduces Renal Tissue Injury During Shock Wave Lithotripsy

2005 ◽  
Vol 173 (4S) ◽  
pp. 300-301
Author(s):  
Michaella E. Maloney ◽  
Pei Zhong ◽  
Charles G. Marguet ◽  
Yufeng F. Zhou ◽  
Jeffrey C. Sung ◽  
...  
Keyword(s):  
Shock Wave ◽  
Treatment Strategy ◽  
Shock Wave Lithotripsy ◽  
Tissue Injury ◽  
Renal Tissue

Factors Influencing Leukocyte Adherence in Microvessels

1977 ◽  
Vol 38 (04) ◽  
pp. 0823-0830 ◽  
Author(s):  
Mayrovttz N. Harvey ◽  
Wiedeman P. Mary ◽  
Ronald F. Tuma
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Tissue Injury ◽  
Threshold Value ◽  
In Vivo Studies ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Subsequent Behavior ◽  
Flow Stasis

SummaryIn vivo studies of the microcirculation of an untraumatized and unanesthetized animal preparation has shown that leukocyte adherence to vascular endothelium is an extremely rare occurrence. Induction of leukocyte adherence can be produced in a variety of ways including direct trauma to the vessels, remote tissue injury via laser irradiation, and denuding the epithelium overlying the observed vessels. The role of blood flow and local hemodynamics on the leukocyte adherence process is quite complex and still not fully understood. From the results reported it may be concluded that blood flow stasis will not produce leukocyte adherence but will augment pre-existing adherence. Studies using 2 quantitative measures of adherence, leukocyte flux and leukocyte velocity have shown these parameters to be affected differently by local hemodynamics. Initial adherence appears to be critically dependent on the magnitude of the blood shear stress at the vessel wall as evidenced by the lack of observable leukocyte flux above some threshold value. Subsequent behavior of the leukocytes as characterized by their average rolling velocity shows no apparent relationship to shear stress but, for low velocities, may be related to the linear blood velocity.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury

1982 ◽  
Vol 60 (11) ◽  
pp. 1415-1424 ◽  
Author(s):  
H. B. Demopoulos ◽  
E. S. Flamm ◽  
M. L. Seligman ◽  
D. D. Pietronigro ◽  
J. Tomasula ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Free Radical ◽  
Tissue Injury ◽  
Functional Restoration ◽  
Radical Reactions ◽  
Free Radical Reactions ◽  
Cord Injury

The hypothesis that pathologic free-radical reactions are initiated and catalyzed in the major central nervous system (CNS) disorders has been further supported by the current acute spinal cord injury work that has demonstrated the appearance of specific, cholesterol free-radical oxidation products. The significance of these products is suggested by the fact that: (i) they increase with time after injury; (ii) their production is curtailed with a steroidal antioxidant; (iii) high antioxidant doses of the steroidal antioxidant which curtail the development of free-radical product prevent tissue degeneration and permit functional restoration. The role of pathologic free-radical reactions is also inferred from the loss of ascorbic acid, a principal CNS antioxidant, and of extractable cholesterol. These losses are also prevented by the steroidal antioxidant. This model system is among others in the CNS which offer distinctive opportunities to study, in vivo, the onset and progression of membrane damaging free-radical reactions within well-defined parameters of time, extent of tissue injury, correlation with changes in membrane enzymes, and correlation with readily measurable in vivo functions.

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