Optogenetic interrogation of neurovascular coupling in the cerebral cortex of transgenic mice

Atry, Farid; Chen, Rex Chin-Hao; Pisaniello, Jane A.; Brodnick, Sarah K.; Suminski, Aaron J.; Novello, Joseph; Ness, Jared P.; Williams, Justin; Pashaie, Ramin

doi:10.1088/1741-2552/aad840

Cited by 9 publications

(13 citation statements)

References 58 publications

(82 reference statements)

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“…Although the dominant view is that blood pulsatility gets dampened before it reaches the microvasculature (O'Rourke and Safar, 2005), recent measurements have challenged this view. Indeed, significant pressure and velocity oscillations have been reported in capillaries down to 4 µm in diameter (Gu et al, 2018;Gurov et al, 2018;Koutsiaris, 2016), and 40-µm-diameter mouse brain arterioles have been shown to exhibit 10% strain at the heartbeat frequency, demonstrating that the pulse penetrates deep into the microvasculature (Atry et al, 2018).…”

Section: Forces Exerted On Pericytesmentioning

confidence: 99%

Pericyte mechanics and mechanobiology

Dessalles

Babataheri

Barakat

2021

Journal of Cell Science

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Pericytes are mural cells of the microvasculature, recognized by their thin processes and protruding cell body. Pericytes wrap around endothelial cells and play a central role in regulating various endothelial functions, including angiogenesis and inflammation. They also serve as a vascular support and regulate blood flow by contraction. Prior reviews have examined pericyte biological functions and biochemical signaling pathways. In this Review, we focus on the role of mechanics and mechanobiology in regulating pericyte function. After an overview of the morphology and structure of pericytes, we describe their interactions with both the basement membrane and endothelial cells. We then turn our attention to biophysical considerations, and describe contractile forces generated by pericytes, mechanical forces exerted on pericytes, and pericyte responses to these forces. Finally, we discuss 2D and 3D engineered in vitro models for studying pericyte mechano-responsiveness and underscore the need for more evolved models that provide improved understanding of pericyte function and dysfunction.

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Section: Forces Exerted On Pericytesmentioning

confidence: 99%

Pericyte mechanics and mechanobiology

Dessalles

Babataheri

Barakat

2021

Journal of Cell Science

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“…Importantly, these mechanical forces are highly dynamic due to blood flow pulsatility. Although pulsatility has traditionally been assumed to be completely dampened by the time blood reaches the microvasculature, recent data challenge this consensus and have reported significant velocity and diameter oscillations even in the smallest capillaries [18][19][20][21][22]. Interestingly, in diseases such as hypertension, the higher pulse pressure penetrates deeper into the vascular tree, further increasing pulsatility in the microvasculature [7,23].…”

Section: Introductionmentioning

confidence: 99%

Luminal flow actuation generates coupled shear and strain in a microvessel-on-chip

et al. 2021

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In the microvasculature, blood flow-derived forces are key regulators of vascular structure and function. Consequently, the development of hydrogel-based microvessel-on-chip systems that strive to mimic the in vivo cellular organization and mechanical environment has received great attention in recent years. However, despite intensive efforts, current microvesselon-chip systems suffer from several limitations, most notably failure to produce physiologically relevant wall strain levels. In this study, a novel microvessel-on-chip based on the templating technique and using luminal flow actuation to generate physiologically relevant levels of wall shear stress and circumferential stretch is presented. Normal forces induced by the luminal pressure compress the surrounding soft collagen hydrogel, dilate the channel, and create large circumferential strain. The fluid pressure gradient in the system drives flow forward and generates realistic pulsatile wall shear stresses. Rigorous characterization of the system reveals the crucial role played by the poroelastic behavior of the hydrogel in determining the magnitudes of the wall shear stress and strain. The experimental measurements are combined with an analytical model of flow in both the lumen and the porous hydrogel to provide an exceptionally versatile user manual for an application-based choice of parameters in microvessels-on-chip. This unique strategy of flow actuation adds a dimension to the capabilities of microvessel-on-chip systems and provides a more general framework for improving hydrogel-based in vitro engineered platforms.

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“…Optogenetics, an advanced method for cell-type-specific manipulation, has been applied to understanding the mechanism of neurovascular coupling. For example, optogenetic neuronal excitation was shown to induce vasodilation (Atry et al, 2018;Krawchuk et al, 2020;Mester et al, 2019;Uhlirova et al, 2016), which was accompanied by an intracellular Ca 2+ decrease in blood vessel cells (Hill et al, 2015). In addition, optogenetic astrocytic activation was shown to increase CBF independent of neural activation (Masamoto et al, 2015;Takata et al, 2018).…”

Section: Introductionmentioning

confidence: 99%