scholarly journals Optogenetic Stimulation of GABA Neurons can Decrease Local Neuronal Activity While Increasing Cortical Blood Flow

2015 ◽  
Vol 35 (10) ◽  
pp. 1579-1586 ◽  
Author(s):  
Eitan Anenberg ◽  
Allen W Chan ◽  
Yicheng Xie ◽  
Jeffrey M LeDue ◽  
Timothy H Murphy

We investigated the link between direct activation of inhibitory neurons, local neuronal activity, and hemodynamics. Direct optogenetic cortical stimulation in the sensorimotor cortex of transgenic mice expressing Channelrhodopsin-2 in GABAergic neurons (VGAT-ChR2) greatly attenuated spontaneous cortical spikes, but was sufficient to increase blood flow as measured with laser speckle contrast imaging. To determine whether the observed optogenetically evoked gamma aminobutyric acid (GABA)-neuron hemodynamic responses were dependent on ionotropic glutamatergic or GABAergic synaptic mechanisms, we paired optogenetic stimulation with application of antagonists to the cortex. Incubation of glutamatergic antagonists directly on the cortex (NBQX and MK-801) blocked cortical sensory evoked responses (as measured with electroencephalography and intrinsic optical signal imaging), but did not significantly attenuate optogenetically evoked hemodynamic responses. Significant light-evoked hemodynamic responses were still present after the addition of picrotoxin (GABA-A receptor antagonist) in the presence of the glutamatergic synaptic blockade. This activation of cortical inhibitory interneurons can mediate large changes in blood flow in a manner that is by and large not dependent on ionotropic glutamatergic or GABAergic synaptic transmission. This supports the hypothesis that activation of inhibitory neurons can increase local cerebral blood flow in a manner that is not entirely dependent on levels of net ongoing neuronal activity.

2011 ◽  
Vol 300 (2) ◽  
pp. F319-F329 ◽  
Author(s):  
Niels-Henrik Holstein-Rathlou ◽  
Olga V. Sosnovtseva ◽  
Alexey N. Pavlov ◽  
William A. Cupples ◽  
Charlotte Mehlin Sorensen ◽  
...  

Tubuloglomerular feedback (TGF) has an important role in autoregulation of renal blood flow and glomerular filtration rate (GFR). Because of the characteristics of signal transmission in the feedback loop, the TGF undergoes self-sustained oscillations in single-nephron blood flow, GFR, and tubular pressure and flow. Nephrons interact by exchanging electrical signals conducted electrotonically through cells of the vascular wall, leading to synchronization of the TGF-mediated oscillations. Experimental studies of these interactions have been limited to observations on two or at most three nephrons simultaneously. The interacting nephron fields are likely to be more extensive. We have turned to laser speckle contrast imaging to measure the blood flow dynamics of 50–100 nephrons simultaneously on the renal surface of anesthetized rats. We report the application of this method and describe analytic techniques for extracting the desired data and for examining them for evidence of nephron synchronization. Synchronized TGF oscillations were detected in pairs or triplets of nephrons. The amplitude and the frequency of the oscillations changed with time, as did the patterns of synchronization. Synchronization may take place among nephrons not immediately adjacent on the surface of the kidney.


2018 ◽  
Vol 12 (1) ◽  
pp. e201800100 ◽  
Author(s):  
Wenzhi Lv ◽  
Yang Wang ◽  
Xiao Chen ◽  
Xiaoxi Fu ◽  
Jinling Lu ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ewa Grudzińska ◽  
Monika Modrzejewska

Myopia is the most common refractive error and the subject of interest of various studies assessing ocular blood flow. Increasing refractive error and axial elongation of the eye result in the stretching and thinning of the scleral, choroid, and retinal tissues and the decrease in retinal vessel diameter, disturbing ocular blood flow. Local and systemic factors known to change ocular blood flow include glaucoma, medications and fluctuations in intraocular pressure, and metabolic parameters. Techniques and tools assessing ocular blood flow include, among others, laser Doppler flowmetry (LDF), retinal function imager (RFI), laser speckle contrast imaging (LSCI), magnetic resonance imaging (MRI), optical coherence tomography angiography (OCTA), pulsatile ocular blood flowmeter (POBF), fundus pulsation amplitude (FPA), colour Doppler imaging (CDI), and Doppler optical coherence tomography (DOCT). Many researchers consistently reported lower blood flow parameters in myopic eyes regardless of the used diagnostic method. It is unclear whether this is a primary change that causes secondary thinning of ocular tissues or quite the opposite; that is, the mechanical stretching of the eye wall reduces its thickness and causes a secondary lower demand of tissues for oxygen. This paper presents a review of studies assessing ocular blood flow in myopes.


2018 ◽  
Vol 45 (2) ◽  
pp. 0207006
Author(s):  
李晨曦 Li Chenxi ◽  
陈文亮 Chen Wenliang ◽  
蒋景英 Jiang Jingying ◽  
范颖 Fan Ying ◽  
杨婧孜 Yang Jingzi ◽  
...  

2020 ◽  
Vol 318 (1) ◽  
pp. H110-H115 ◽  
Author(s):  
Jahyun Kim ◽  
Warren D. Franke ◽  
James A. Lang

One week of daily remote ischemic preconditioning (RIPC) improves cutaneous vasodilatory (VD) function. However, the underlying mechanisms and the number of sessions needed to optimize this adaptive response remain unclear. We hypothesized that the responses to localized heating of the skin will be greater after 2 wk as opposed to 1 wk of RIPC. Furthermore, 2 wk of repeated RIPC will augment cutaneous VD responses to thermal and pharmacological stimuli. In methods, twenty-four participants (24 ± 2 yr; 13 men, 11 women) performed repeated RIPC (7 daily sessions over 1 wk, n = 11; 12 sessions over 2 wk, n = 13), consisting of four repetitions of 5 min of arm blood flow occlusion separated by 5 min reperfusion. Laser speckle contrast imaging was used to measure skin blood flow responses, in perfusion units (PU), to local heating (Tloc = 42°C), acetylcholine (ACh), and sodium nitroprusside (SNP) before and after repeated RIPC. Data were expressed as cutaneous vascular conductance (CVC, in PU/mmHg). In results, the VD response to local heating increased after RIPC (∆CVC from baseline; 1 wk: 0.94 ± 0.11 to 1.19 ± 0.15, 2 wk: 1.18 ± 0.07 to 1.33 ± 0.10 PU/mmHg; P < 0.05) but the ∆CVC did not differ between weeks. SNP-induced VD increased after 2 wk of RIPC (∆CVC; 0.34 ± 0.07 to 0.63 ± 0.11 PU/mmHg; P < 0.05), but ACh-induced VD did not. In conclusion, repeated RIPC improves local heating- and SNP-mediated cutaneous VD. When compared with 1 wk of RIPC, 2 wk of RIPC does not induce further improvements in cutaneous VD function. NEW & NOTEWORTHY Repeated RIPC increases the cutaneous vasodilatory response to local heating and to sodium nitroprusside but not to acetylcholine. Thus, endothelial-independent and local heating-mediated cutaneous vasodilation are improved following RIPC. However, 2 wk of RIPC sessions are not more effective than 1 wk of RIPC sessions in enhancing local heating-mediated cutaneous vasodilation.


2015 ◽  
Vol 118 (3) ◽  
pp. 344-354 ◽  
Author(s):  
Claire A. Sand ◽  
Anna Starr ◽  
Catherine D. E. Wilder ◽  
Olena Rudyk ◽  
Domenico Spina ◽  
...  

Sepsis and sepsis-associated multiorgan failure represent the major cause of mortality in intensive care units worldwide. Cardiovascular dysfunction, a key component of sepsis pathogenesis, has received much research interest, although research translatability remains severely limited. There is a critical need for more comprehensive preclinical sepsis models, with more clinically relevant end points, such as microvascular perfusion. The purpose of this study was to compare microcirculatory blood flow measurements, using a novel application of laser speckle contrast imaging technology, with more traditional hemodynamic end points, as part of a multiparameter monitoring system in preclinical models of sepsis. Our aim, in measuring mesenteric blood flow, was to increase the prognostic sensitivity of preclinical studies. In two commonly used sepsis models (cecal ligation and puncture, and lipopolysaccharide), we demonstrate that blood pressure and cardiac output are compromised postsepsis, but subsequently stabilize over the 24-h recording period. In contrast, mesenteric blood flow continuously declines in a time-dependent manner and in parallel with the development of metabolic acidosis and organ dysfunction. Importantly, these microcirculatory perturbations are reversed by fluid resuscitation, a mainstay intervention associated with improved outcome in patients. These data suggest that global hemodynamics are maintained at the expense of the microcirculation and are, therefore, not sufficiently predictive of outcome. We demonstrate that microcirculatory blood flow is a more sensitive biomarker of sepsis syndrome progression and believe that incorporation of this biomarker into preclinical models will facilitate sophisticated proof-of-concept studies for novel sepsis interventions, providing more robust data on which to base future clinical trials.


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