Abstract P604: Astrocyte-dependent Regulation of Vascular Tone: Role in Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Juan Manuel Ramiro-Diaz ◽  
Ki Jung Kim ◽  
Jessica A Filosa
Keyword(s):  
Vascular Tone ◽  
Structural Changes ◽  
Neurovascular Unit ◽  
Brain Slices ◽  
Vascular Cognitive Impairment ◽  
Vascular Density ◽  
Aqp4 Expression ◽  
Functional Changes ◽  
Functional Studies ◽  
Underlying Mechanisms

Clinical studies support that untreated hypertension (HT) accelerates the development of vascular cognitive impairment (VCI). Yet, the underlying mechanisms for VCI are not known. In a recent study we demonstrated the role of astrocytes in the regulation of parenchymal arteriole (PA) steady-state vascular tone. Here we hypothesized hypertension results in structural and functional changes to the neurovascular unit resulting in enhanced astrocytic TRPV4 channel-dependent Ca 2+ increases contributing to augmented pressure-induced PA constriction . Functional studies were conducted in brain slices from angiotensin II (AngII) treated mice (600 ng/Kg/min, 28 days). PA arterioles within brain slices were perfused and pressurized and myogenic-evoked diameter changes measured using video microscopy. In addition, using the GLAST-CreERT2 ; R26-lsl-GCaMP3 mice we measure myogenic-evoked Ca 2+ changes in perivascular astrocytes. We demonstrate that HT increases pressure-induced PA tone by 11.14% at 30 mmHg and 12.97% at 60 mmHg (10.88 to 22.02 and 15.46 to 28.43% of tone, P<0.05 and P<0.01, respectively). In ANG II-treated mice, PA myogenic-evoked responses significantly increased astrocytic Ca 2+ oscillations frequency (119.4%, 0.0366 to 0.0803 Hz, P<0.0001). A significant increase in astrocytic Ca 2+ oscillation frequency was also observed after 2 min of AngII (500 nM) bath application (44.8%, 0.0366 to 0.053 Hz, P<0.01) in brain slices from AngII treated mice. Furthermore, using the model of spontaneous hypertensive rat (SHR) we observed that HT differentially increases vascular density and the number of vascular pericytes in cortical layers with highest neuronal densities (L III-V). Finally, while aquaporin 4 (AQP4) expression pattern was not different in the gray matter of SHR compared with WKY rats, a significant increase in unpolarized AQP4 expression was observed in the white matter of SHR. Taken together, this evidence indicates that HT induces functional and structural changes to the neurovascular unit favoring the development of regional brain hypoperfusion likely contributing to the development of VCI.

Macular capillary plexuses after macular hole surgery: an optical coherence tomography angiography study

2017 ◽  
Vol 102 (7) ◽  
pp. 966-970 ◽  
Author(s):  
Yoon Jeon Kim ◽  
Jaehyuck Jo ◽  
Joo Yong Lee ◽  
Young Hee Yoon ◽  
June-Gone Kim
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Hole ◽  
Structural Changes ◽  
Foveal Avascular Zone ◽  
Vascular Density ◽  
Optical Coherence ◽  
Foveal Thickness ◽  
Functional Changes ◽  
Spectral Domain Oct ◽  
En Face

AimsTo investigate the structural changes of the superficial capillary plexuses (SCP) and deep capillary plexuses (DCP) using optical coherence tomography (OCT) angiography (OCTA) in patients with idiopathic macular hole (MH) after surgery, determine the factors related to changes of macular capillary plexuses and evaluate its association with postoperative visual outcomes.MethodsThirty-three patients with unilateral MH who were followed for ≥6 months after surgery were included. Ophthalmologic evaluations included best corrected visual acuity (BCVA) and spectral-domain OCT before surgery and 6 months postsurgery. En face OCTA images were obtained for both eyes at 6 months postsurgery, and the postoperative foveal avascular zone (FAZ) area and parafoveal vascular density were identified.ResultsCompared with fellow eyes, eyes after MH surgery had a smaller FAZ area in both SCP and DCP (p<0.05 for all). The FAZ area was positively correlated with postoperative foveal thickness of the whole, inner and outer layers (p<0.05 for all). In the parafoveal region, eyes after MH surgery had a tendency to have lower parafoveal vascular density, particularly in DCP (p=0.019). The parafoveal vascular density in DCP was positively correlated with retinal thickness of the whole, inner and outer layers (p<0.05 for all). Correlations between BCVA and FAZ area in both SCP and DCP were significant 6 months after MH surgery (p<0.05 for all).ConclusionAssessment of macular capillary plexuses using OCTA may be useful for monitoring retinal structural and functional changes in MH.

Daily short-period gravitation can prevent functional and structural changes in arteries of simulated microgravity rats

2004 ◽  
Vol 97 (3) ◽  
pp. 1022-1031 ◽  
Author(s):  
Biao Sun ◽  
Li-Fan Zhang ◽  
Fang Gao ◽  
Xiao-Wu Ma ◽  
Miao-Li Zhang ◽  
...  
Keyword(s):  
Structural Changes ◽  
Simulated Microgravity ◽  
Functional Changes ◽  
Functional Studies ◽  
Morphological Studies ◽  
Gravitational Loading ◽  
Tibial Arteries ◽  
Short Period ◽  
Anterior Tibial ◽  
Head Up Tilt

This study was designed to clarify whether simulated microgravity-induced differential adaptational changes in cerebral and hindlimb arteries could be prevented by daily short-period restoration of the normal distribution of transmural pressure across arterial vasculature by either dorsoventral or footward gravitational loading. Tail suspension (Sus) for 28 days was used to simulate cardiovascular deconditioning due to microgravity. Daily standing (STD) for 1, 2, or 4 h, or +45° head-up tilt (HUT) for 2 or 4 h was used to provide short-period dorsoventral or footward gravitational loading as countermeasure. Functional studies showed that Sus alone induced an enhancement and depression in vasoconstrictor responsiveness of basilar and femoral arterial rings, respectively, as previously reported. These differential functional alterations can be prevented by either of the two kinds of daily gravitational loading treatments. Surprisingly, daily STD for as short as 1 h was sufficient to prevent the differential functional changes that might occur due to Sus alone. In morphological studies, the effectiveness of daily 4-h HUT or 1-h STD in preventing the differential remodeling changes in the structure of basilar and anterior tibial arteries induced by Sus alone was examined by histomorphometry. The results showed that both the hypertrophic and atrophic changes that might occur, respectively, in cerebral and hindlimb arteries due to Sus alone were prevented not only by daily HUT for 4 h but also by daily STD even for 1 h. These data indicate that daily gravitational loading by STD for as short as 1 h is sufficient to prevent differential adaptational changes in function and structure of vessels in different anatomic regions induced by a medium-term simulated microgravity.

scholarly journals Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment

GeroScience ◽  
2021 ◽  
Author(s):  
Ki Jung Kim ◽  
Juan Ramiro Diaz ◽  
Jessica L. Presa ◽  
P. Robinson Muller ◽  
Michael W. Brands ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Pyramidal Neurons ◽  
Ex Vivo ◽  
Neurovascular Unit ◽  
Vascular Cognitive Impairment ◽  
Early Event ◽  
Functional Changes ◽  
Post Surgery ◽  
Arteriolar Tone

AbstractChronic hypoperfusion is a key contributor to cognitive decline and neurodegenerative conditions, but the cellular mechanisms remain ill-defined. Using a multidisciplinary approach, we sought to elucidate chronic hypoperfusion-evoked functional changes at the neurovascular unit. We used bilateral common carotid artery stenosis (BCAS), a well-established model of vascular cognitive impairment, combined with an ex vivo preparation that allows pressurization of parenchymal arterioles in a brain slice. Our results demonstrate that mild (~ 30%), chronic hypoperfusion significantly altered the functional integrity of the cortical neurovascular unit. Although pial cerebral perfusion recovered over time, parenchymal arterioles progressively lost tone, exhibiting significant reductions by day 28 post-surgery. We provide supportive evidence for reduced adenosine 1 receptor-mediated vasoconstriction as a potential mechanism in the adaptive response underlying the reduced baseline tone in parenchymal arterioles. In addition, we show that in response to the neuromodulator adenosine, the action potential frequency of cortical pyramidal neurons was significantly reduced in all groups. However, a significant decrease in adenosine-induced hyperpolarization was observed in BCAS 14 days. At the microvascular level, constriction-induced inhibition of pyramidal neurons was significantly compromised in BCAS mice. Collectively, these results suggest that BCAS uncouples vessel-to-neuron communication—vasculo-neuronal coupling—a potential early event in cognitive decline.

scholarly journals Astroglial Integrins in the Development and Regulation of Neurovascular Units

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hironobu Tanigami ◽  
Takayuki Okamoto ◽  
Yuichi Yasue ◽  
Motomu Shimaoka
Keyword(s):  
Central Nervous System ◽  
Cell Adhesion Molecules ◽  
Energy Demand ◽  
Vascular Tone ◽  
Neurovascular Unit ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
The Brain ◽  
Signaling Activity ◽  
Cerebral Vascular

In the neurovascular units of the central nervous system, astrocytes form extensive networks that physically and functionally connect the neuronal synapses and the cerebral vascular vessels. This astrocytic network is thought to be critically important for coupling neuronal signaling activity and energy demand with cerebral vascular tone and blood flow. To establish and maintain this elaborate network, astrocytes must precisely calibrate their perisynaptic and perivascular processes in order to sense and regulate neuronal and vascular activities, respectively. Integrins, a prominent family of cell-adhesion molecules that support astrocytic migration in the brain during developmental and normal adult stages, have been implicated in regulating the integrity of the blood brain barrier and the tripartite synapse to facilitate the formation of a functionally integrated neurovascular unit. This paper describes the significant roles that integrins and connexins play not only in regulating astrocyte migration during the developmental and adult stages of the neurovascular unit, but also in general health and in such diseases as hepatic encephalopathy.

scholarly journals Retinal functional imager (RFI): Non-invasive functional imaging of the retina

2013 ◽  
Vol 5 (2) ◽  
pp. 250-257 ◽  
Author(s):  
Sunil Ganekal
Keyword(s):  
Functional Imaging ◽  
Structural Changes ◽  
Imaging System ◽  
Retinal Blood Flow ◽  
Capillary Perfusion ◽  
Functional Changes ◽  
Non Invasive ◽  
Retinal Disorders ◽  
Retinal Blood Flow Velocity ◽  
Perfusion Maps

Retinal functional imager (RFI) is a unique non-invasive functional imaging system with novel capabilities for visualizing the retina. The objective of this review was to show the utility of non-invasive functional imaging in various disorders. Electronic literature search was carried out using the websites www.pubmed.gov and www.google.com. The search words were retinal functional imager and non-invasive retinal imaging used in combination. The articles published or translated into English were studied. The RFI directly measures hemodynamic parameters such as retinal blood-flow velocity, oximetric state, metabolic responses to photic activation and generates capillary perfusion maps (CPM) that provides retinal vasculature detail similar to flourescein angiography. All of these parameters stand in a direct relationship to the function and therefore the health of the retina, and are known to be degraded in the course of retinal diseases. Detecting changes in retinal function aid early diagnosis and treatment as functional changes often precede structural changes in many retinal disorders. Nepal J Ophthalmol 2013; 5(10): 250-257 DOI: http://dx.doi.org/10.3126/nepjoph.v5i2.8738

Vasodilatory effects and underlying mechanisms of the ethyl acetate extracts from Gastrodia elata

2017 ◽  
Vol 95 (5) ◽  
pp. 564-571 ◽  
Author(s):  
Rong Dai ◽  
Ting Wang ◽  
Xiaoqin Si ◽  
Yuanyuan Jia ◽  
Lili Wang ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Vascular Tone ◽  
Ethyl Acetate Extract ◽  
Chemical Compounds ◽  
Rat Aorta ◽  
Gastrodia Elata ◽  
Vasodilatory Effect ◽  
Intracellular Ca ◽  
Underlying Mechanisms ◽  
Ethyl Acetate Extracts

The objective of this study was to assess the ethyl acetate extracts of Gastrodia elata Blume (GEB) on vascular tone and the mechanisms involved. GEB was extracted with 95% EtOH followed by a further extraction with ethyl acetate. The effects of GEB and its ingredients on the isometric tensions of the aortic rings from rats were measured. The ethyl acetate extract of GEB induced a vasodilatory effect on rat aorta, which was partially dependent on endothelium. Four chemical compounds isolated from GEB were identified as 3,4-dihydroxybenzaldehyde (DB), 4-hydroxybenzaldehyde (HB), 4-methoxybenzyl alcohol (MA), and 4,4′-dihydroxydiphenyl methane (DM), respectively. All of these compounds induced vasodilatations, which were dependent on the endothelium to different degrees. After pretreatment with Nω-nitro-l-arginine methyl ester, indomethacin, or methylene blue, the vasodilatations induced by DB, HB, and MA were significantly decreased. In addition, the contractions of the rat aortic rings due to Ca2+ influx and intracellular Ca2+ release were also inhibited by DM. Furthermore, the administration of DB significantly enhanced the productions of nitric oxide (NO) and the activities of the endothelial NO synthase in aorta and in endothelial cells. Thus, GEB may play an important role in the amelioration of hypertension by modulating vascular tones.

Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling

2005 ◽  
Vol 99 (2) ◽  
pp. 634-641 ◽  
Author(s):  
Linhong Deng ◽  
Nigel J. Fairbank ◽  
Darren J. Cole ◽  
Jeffrey J. Fredberg ◽  
Geoffrey N. Maksym
Keyword(s):  
Smooth Muscle ◽  
Mechanical Stress ◽  
Applied Stress ◽  
Airway Smooth Muscle ◽  
Cell Activation ◽  
Structural Changes ◽  
Muscle Tone ◽  
Residual Effects ◽  
Cell Stiffness ◽  
Functional Changes

The application of mechanical stresses to the airway smooth muscle (ASM) cell causes time-dependent cytoskeletal stiffening and remodeling (Deng L, Fairbank NJ, Fabry B, Smith PG, and Maksym GN. Am J Physiol Cell Physiol 287: C440–C448, 2004). We investigated here the extent to which these behaviors are modulated by the state of cell activation (tone). Localized mechanical stress was applied to the ASM cell in culture via oscillating beads (4.5 μm) that were tightly bound to the actin cytoskeleton (CSK). Tone was reduced from baseline level using a panel of relaxant agonists (10−3 M dibutyryl cAMP, 10−4 M forskolin, or 10−6 M formoterol). To assess functional changes, we measured cell stiffness (G′) using optical magnetic twisting cytometry, and to assess structural changes of the CSK we measured actin accumulation in the neighborhood of the bead. Applied mechanical stress caused a twofold increase in G′ at 120 min. After cessation of applied stress, G′ diminished only 24 ± 6% (mean ± SE) at 1 h, leaving substantial residual effects that were largely irreversible. However, applied stress-induced stiffening could be prevented by ablation of tone. Ablation of tone also inhibited the amount of actin accumulation induced by applied mechanical stress ( P < 0.05). Thus the greater the contractile tone, the greater was applied stress-induced CSK stiffening and remodeling. As regards pathobiology of asthma, this suggests a maladaptive positive feedback in which tone potentiates ASM remodeling and stiffening that further increases stress and possibly leads to worsening airway function.

Myosin thick filament lability induced by mechanical strain in airway smooth muscle

2001 ◽  
Vol 90 (5) ◽  
pp. 1811-1816 ◽  
Author(s):  
Kuo-Hsing Kuo ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Lincoln E. Ford ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cross Sections ◽  
Structural Changes ◽  
Isometric Force ◽  
Mechanical Strain ◽  
Thick Filament ◽  
Functional Changes ◽  
Thick Filaments ◽  
Length Changes

Airway smooth muscle adapts to different lengths with functional changes that suggest plastic alterations in the filament lattice. To look for structural changes that might be associated with this plasticity, we studied the relationship between isometric force generation and myosin thick filament density in cell cross sections, measured by electron microscope, after length oscillations applied to the relaxed porcine trachealis muscle. Muscles were stimulated regularly for 12 s every 5 min. Between two stimulations, the muscles were submitted to repeated passive ±30% length changes. This caused tetanic force and thick-filament density to fall by 21 and 27%, respectively. However, in subsequent tetani, both force and filament density recovered to preoscillation levels. These findings indicate that thick filaments in airway smooth muscle are labile, depolymerization of the myosin filaments can be induced by mechanical strain, and repolymerization of the thick filaments underlies force recovery after the oscillation. This thick-filament lability would greatly facilitate plastic changes of lattice length and explain why airway smooth muscle is able to function over a large length range.

scholarly journals Choroidal vessel density in unilateral hyperopic amblyopia using en-face optical coherence tomography

2020 ◽  
Author(s):  
Syunsuke Araki ◽  
Atsushi Miki ◽  
Katsutoshi Goto ◽  
Tsutomu Yamashita ◽  
Tsuyoshi Yoneda ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Normal Control ◽  
Structural Changes ◽  
Vascular Density ◽  
Optical Coherence ◽  
Swept Source ◽  
3 Dimensional ◽  
Face Images ◽  
En Face ◽  
Normal Controls

Abstract Background Structural changes of the choroid, such as choroidal thickening, have been indicated in amblyopic eyes with hyperopic anisometropia as compared to fellow or healthy eyes. The purpose of the present study was to investigate choroidal vascular density (CVD) in children with unilateral hyperopic amblyopia.Methods This study included 88 eyes of 44 patients with unilateral amblyopia due to hyperopic anisometropia with or without strabismus and 29 eyes of 29 age-matched normal controls. The CVD of Haller's layer was quantified from en-face images constructed by 3-dimensional swept-source optical coherence tomography images flattened relative to Bruch's membrane. The analysis area was a 3×3-mm square of macula after magnification correction. Relationships between CVD and other parameters [best-corrected visual acuity (BCVA), refractive error and subfoveal choroidal thickness (SFCT)] were investigated, and CVDs were compared between amblyopic, fellow, and normal control eyes.Results Mean CVD was 59.11 ± 0.66% in amblyopic eyes, 59.23 ± 0.81% in fellow eyes, and 59.29 ± 0.74% in normal control eyes. CVD showed a significant positive relationship with SFCT (p=0.004), but no relationships with other parameters. No significant differences in CVD were evident among amblyopic, fellow, and normal control eyes after adjusting for SFCT (p=0.502).Conclusions CVD was unrelated to BCVA, and CVD did not differ significantly among amblyopic, fellow and normal control eyes. These results suggest that the local CVD of Haller's layer is unaffected in unilateral hyperopic amblyopic eyes.

scholarly journals Regional synapse gain and loss accompany memory formation in larval zebrafish

2022 ◽  
Vol 119 (3) ◽  
pp. e2107661119
Author(s):  
William P. Dempsey ◽  
Zhuowei Du ◽  
Anna Nadtochiy ◽  
Colton D. Smith ◽  
Karl Czajkowski ◽  
...  
Keyword(s):  
Classical Conditioning ◽  
Structural Changes ◽  
Memory Formation ◽  
Excitatory Synapses ◽  
Microscopy Imaging ◽  
Functional Changes ◽  
Larval Zebrafish ◽  
Before And After ◽  
Synaptic Changes ◽  
With Memory

Defining the structural and functional changes in the nervous system underlying learning and memory represents a major challenge for modern neuroscience. Although changes in neuronal activity following memory formation have been studied [B. F. Grewe et al., Nature 543, 670–675 (2017); M. T. Rogan, U. V. Stäubli, J. E. LeDoux, Nature 390, 604–607 (1997)], the underlying structural changes at the synapse level remain poorly understood. Here, we capture synaptic changes in the midlarval zebrafish brain that occur during associative memory formation by imaging excitatory synapses labeled with recombinant probes using selective plane illumination microscopy. Imaging the same subjects before and after classical conditioning at single-synapse resolution provides an unbiased mapping of synaptic changes accompanying memory formation. In control animals and animals that failed to learn the task, there were no significant changes in the spatial patterns of synapses in the pallium, which contains the equivalent of the mammalian amygdala and is essential for associative learning in teleost fish [M. Portavella, J. P. Vargas, B. Torres, C. Salas, Brain Res. Bull. 57, 397–399 (2002)]. In zebrafish that formed memories, we saw a dramatic increase in the number of synapses in the ventrolateral pallium, which contains neurons active during memory formation and retrieval. Concurrently, synapse loss predominated in the dorsomedial pallium. Surprisingly, we did not observe significant changes in the intensity of synaptic labeling, a proxy for synaptic strength, with memory formation in any region of the pallium. Our results suggest that memory formation due to classical conditioning is associated with reciprocal changes in synapse numbers in the pallium.

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