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Precapillary sphincters maintain perfusion in the cerebral cortex.

ABSTRACT: Active nerve cells release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling and the basis of BOLD functional neuroimaging signals. Here, we reveal a mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and first order capillary, linking blood flow in capillaries to the arteriolar inflow. The sphincters are encircled by contractile mural cells, which are capable of bidirectional control of the length and width of the enclosed vessel segment. The hemodynamic consequence is that precapillary sphincters can generate the largest changes in the cerebrovascular flow resistance of all brain vessel segments, thereby controlling capillary flow while protecting the downstream capillary bed and brain tissue from adverse pressure fluctuations. Cortical spreading depolarization constricts sphincters and causes vascular trapping of blood cells. Thus, precapillary sphincters are bottlenecks for brain capillary blood flow.

SUBMITTER: Grubb S

PROVIDER: S-EPMC6971292 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Precapillary sphincters maintain perfusion in the cerebral cortex.

Grubb Søren S Cai Changsi C Hald Bjørn O BO Khennouf Lila L Murmu Reena Prity RP Jensen Aske G K AGK Fordsmann Jonas J Zambach Stefan S Lauritzen Martin M

Nature communications 20200120 1

Active nerve cells release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling and the basis of BOLD functional neuroimaging signals. Here, we reveal a mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and first order capillary, linking blood flow in capillaries to the arteriolar inflow. The sphincters are encircled by contractile mural cells, which are capa ...[more]

PMID: 31959752

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Project description:Departures of normal blood flow and metabolite distribution from the cerebral microvasculature into neuronal tissue have been implicated with age-related neurodegeneration. Mathematical models informed by spatially and temporally distributed neuroimage data are becoming instrumental for reconstructing a coherent picture of normal and pathological oxygen delivery throughout the brain. Unfortunately, current mathematical models of cerebral blood flow and oxygen exchange become excessively large in size. They further suffer from boundary effects due to incomplete or physiologically inaccurate computational domains, numerical instabilities due to enormous length scale differences, and convergence problems associated with condition number deterioration at fine mesh resolutions. Our proposed simple finite volume discretization scheme for blood and oxygen microperfusion simulations does not require expensive mesh generation leading to the critical benefit that it drastically reduces matrix size and bandwidth of the coupled oxygen transfer problem. The compact problem formulation yields rapid and stable convergence. Moreover, boundary effects can effectively be suppressed by generating very large replica of the cortical microcirculation in silico using an image-based cerebrovascular network synthesis algorithm, so that boundaries of the perfusion simulations are far removed from the regions of interest. Massive simulations over sizeable portions of the cortex with feature resolution down to the micron scale become tractable with even modest computer resources. The feasibility and accuracy of the novel method is demonstrated and validated with in vivo oxygen perfusion data in cohorts of young and aged mice. Our oxygen exchange simulations quantify steep gradients near penetrating blood vessels and point towards pathological changes that might cause neurodegeneration in aged brains. This research aims to explain mechanistic interactions between anatomical structures and how they might change in diseases or with age. Rigorous quantification of age-related changes is of significant interest because it might aide in the search for imaging biomarkers for dementia and Alzheimer's disease.

Project description:Purpose: The present study used near-infrared spectroscopy to investigate the relationships between cerebral oxygen metabolism and perfusion in the prefrontal cortex (PFC) during exercises of different intensities. Methods: A total of 12 recreationally active men (age 24 ± 6 years) were enrolled. They performed 17 min of low-intensity exercise (ExL), followed by 3 min of moderate-intensity exercise (ExM) at constant loads. Exercise intensities for ExL and ExM corresponded to 30% and 45% of the participants' heart rate reserve, respectively. Cardiovascular and respiratory parameters were measured. We used near-infrared time-resolved spectroscopy (TRS) to measure the cerebral hemoglobin oxygen saturation (ScO2) and total hemoglobin concentration ([HbT]), which can indicate the cerebral blood volume (CBV). As the cerebral metabolic rate for oxygen (CMRO2) is calculated using cerebral blood flow (CBF) and ScO2, we assumed a constant power law relationship between CBF and CBV based on investigations by positron emission tomography (PET). We estimated the relative changes in CMRO2 (rCMRO2) and CBV (rCBV) from the baseline. During ExL and ExM, the rate of perceived exertion was monitored, and alterations in the subjects' mood induced by exercise were evaluated using the Profile of Moods Scale-Brief. Results: Three minutes after exercise initiation, ScO2 decreased and rCMRO2 surpassed rCBV in the left PFC. When ExL changed to ExM, cardiovascular variables and the sense of effort increased concomitantly with an increase in [HbT] but not in ScO2, and the relationship between rCMRO2 and rCBV was dissociated in both sides of the PFC. Immediately after ExM, [HbT], and ScO2 increased, and the disassociation between rCMRO2 and rCBV was prominent in both sides of the PFC. While blood pressure decreased and a negative mood state was less prominent following ExM compared with that at rest, ScO2 decreased 15 min after exercise and rCMRO2 surpassed rCBV in the left PFC. Conclusion: Dissociated coupling between cerebral oxidative metabolism and perfusion in the PFC was consistent with the effort required for increased exercise intensity and associated with post-exercise hypotension and altered mood status after exercise. Our result demonstrates the first preliminary results dealing with the coupling between cerebral oxidative metabolism and perfusion in the PFC using TRS.

Project description:IntroductionThe pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.MethodsWe investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100beta, and cortisol were measured during each data acquisition.ResultsData from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100beta (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).ConclusionIn this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100beta and cortisol in the diagnosis of sepsis-associated delirium are warranted.Trial registrationClinicalTrials.gov NCT00410111.

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Precapillary sphincters maintain perfusion in the cerebral cortex.

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Precapillary sphincters maintain perfusion in the cerebral cortex.

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