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Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation.Physiological Reviews Oct 2021Brain function critically depends on a close matching between metabolic demands, appropriate delivery of oxygen and nutrients, and removal of cellular waste. This... (Review)
Review
Brain function critically depends on a close matching between metabolic demands, appropriate delivery of oxygen and nutrients, and removal of cellular waste. This matching requires continuous regulation of cerebral blood flow (CBF), which can be categorized into four broad topics: ) autoregulation, which describes the response of the cerebrovasculature to changes in perfusion pressure; ) vascular reactivity to vasoactive stimuli [including carbon dioxide (CO)]; ) neurovascular coupling (NVC), i.e., the CBF response to local changes in neural activity (often standardized cognitive stimuli in humans); and ) endothelium-dependent responses. This review focuses primarily on autoregulation and its clinical implications. To place autoregulation in a more precise context, and to better understand integrated approaches in the cerebral circulation, we also briefly address reactivity to CO and NVC. In addition to our focus on effects of perfusion pressure (or blood pressure), we describe the impact of select stimuli on regulation of CBF (i.e., arterial blood gases, cerebral metabolism, neural mechanisms, and specific vascular cells), the interrelationships between these stimuli, and implications for regulation of CBF at the level of large arteries and the microcirculation. We review clinical implications of autoregulation in aging, hypertension, stroke, mild cognitive impairment, anesthesia, and dementias. Finally, we discuss autoregulation in the context of common daily physiological challenges, including changes in posture (e.g., orthostatic hypotension, syncope) and physical activity.
Topics: Animals; Cerebrovascular Circulation; Cerebrovascular Disorders; Homeostasis; Humans; Nervous System Diseases; Neurovascular Coupling
PubMed: 33769101
DOI: 10.1152/physrev.00022.2020 -
Nature Neuroscience Sep 2021The brain is supplied by an elaborate vascular network that originates extracranially and reaches deep into the brain. The concept of the neurovascular unit provides a... (Review)
Review
The brain is supplied by an elaborate vascular network that originates extracranially and reaches deep into the brain. The concept of the neurovascular unit provides a useful framework to investigate how neuronal signals regulate nearby microvessels to support the metabolic needs of the brain, but it does not consider the role of larger cerebral arteries and systemic vasoactive signals. Furthermore, the recently emerged molecular heterogeneity of cerebrovascular cells indicates that there is no prototypical neurovascular unit replicated at all levels of the vascular network. Here, we examine the cellular and molecular diversity of the cerebrovascular tree and the relative contribution of systemic and brain-intrinsic factors to neurovascular function. Evidence supports the concept of a 'neurovascular complex' composed of segmentally diverse functional modules that implement coordinated vascular responses to central and peripheral signals to maintain homeostasis of the brain. This concept has major implications for neurovascular regulation in health and disease and for brain imaging.
Topics: Animals; Brain; Cerebrovascular Circulation; Homeostasis; Humans; Neurovascular Coupling
PubMed: 34354283
DOI: 10.1038/s41593-021-00904-7 -
Journal of Cerebral Blood Flow and... Dec 2018Administration of anesthetic agents fundamentally shifts the responsibility for maintenance of homeostasis from the patient and their intrinsic physiological regulatory... (Review)
Review
Administration of anesthetic agents fundamentally shifts the responsibility for maintenance of homeostasis from the patient and their intrinsic physiological regulatory mechanisms to the anesthesiologist. Continuous delivery of oxygen and nutrients to the brain is necessary to prevent irreversible injury and arises from a complex series of regulatory mechanisms that ensure uninterrupted cerebral blood flow. Our understanding of these regulatory mechanisms and the effects of anesthetics on them has been driven by the tireless work of pioneers in the field. It is of paramount importance that the anesthesiologist shares this understanding. Herein, we will review the physiological determinants of cerebral blood flow and how delivery of anesthesia impacts these processes.
Topics: Anesthesia; Anesthetics; Animals; Brain; Cerebrovascular Circulation; Humans; Neuroprotection
PubMed: 30009645
DOI: 10.1177/0271678X18789273 -
Critical Care (London, England) Sep 2016Volume infusions are one of the commonest clinical interventions in critically ill patients yet the relationship of volume to cardiac output is not well understood.... (Review)
Review
Volume infusions are one of the commonest clinical interventions in critically ill patients yet the relationship of volume to cardiac output is not well understood. Blood volume has a stressed and unstressed component but only the stressed component determines flow. It is usually about 30 % of total volume. Stressed volume is relatively constant under steady state conditions. It creates an elastic recoil pressure that is an important factor in the generation of blood flow. The heart creates circulatory flow by lowering the right atrial pressure and allowing the recoil pressure in veins and venules to drain blood back to the heart. The heart then puts the volume back into the systemic circulation so that stroke return equals stroke volume. The heart cannot pump out more volume than comes back. Changes in cardiac output without changes in stressed volume occur because of changes in arterial and venous resistances which redistribute blood volume and change pressure gradients throughout the vasculature. Stressed volume also can be increased by decreasing vascular capacitance, which means recruiting unstressed volume into stressed volume. This is the equivalent of an auto-transfusion. It is worth noting that during exercise in normal young males, cardiac output can increase five-fold with only small changes in stressed blood volume. The mechanical characteristics of the cardiac chambers and the circulation thus ultimately determine the relationship between volume and cardiac output and are the subject of this review.
Topics: Blood Circulation; Blood Pressure; Blood Volume; Cardiac Output; Humans; Stroke Volume
PubMed: 27613307
DOI: 10.1186/s13054-016-1438-7 -
Circulation Journal : Official Journal... Aug 2022Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant...
Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD ("primary" microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.
Topics: Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Humans; Microcirculation; Microvascular Angina; Myocardial Ischemia
PubMed: 34759123
DOI: 10.1253/circj.CJ-21-0848 -
Trends in Endocrinology and Metabolism:... Feb 2021Blood flow restriction resistance training (BFRT) employs partial vascular occlusion of exercising muscles via inflation cuffs. Compared with high-load resistance... (Review)
Review
Blood flow restriction resistance training (BFRT) employs partial vascular occlusion of exercising muscles via inflation cuffs. Compared with high-load resistance training, mechanical load is markedly reduced with BFRT, but induces similar gains in muscle mass and strength. BFRT is thus an effective training strategy for people with physical limitations. Recent research indicates that BFRT has beneficial effects on glucose and mitochondrial metabolism. BFRT may therefore qualify as a valuable exercise alternative for individuals with type 2 diabetes (T2D), a disorder characterized by impaired glucose metabolism, musculoskeletal decline, and exacerbated progression of sarcopenia. This review covers the effects of BFRT in healthy populations and in persons with impaired physical fitness, the mechanisms of action of this novel training modality, and possible applications for individuals with T2D.
Topics: Blood Circulation; Diabetes Mellitus, Type 2; Humans; Muscle Strength; Muscle, Skeletal; Resistance Training
PubMed: 33358931
DOI: 10.1016/j.tem.2020.11.010 -
Neurology India 2021Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and... (Review)
Review
BACKGROUND
Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions.
OBJECTIVE
This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus.
CONCLUSIONS
Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.
Topics: Cerebrovascular Circulation; Hemodynamics; Humans; Hydrocephalus; Models, Theoretical
PubMed: 35102977
DOI: 10.4103/0028-3886.332259 -
Journal of the American Heart... Jun 2023Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular...
Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. Methods and Results Mice implanted with chronic cranial windows were trained for awake head-fixation before experiments. One-hour occlusion of the anterior middle cerebral artery branch was induced using single-vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion-fixed tissue by labeling lectin and platelet-derived growth factor receptor β. Arterial occlusion induced multiple spreading depolarizations over 1 hour associated with substantially reduced blood flow in the peri-ischemic cortex. Approximately half of the capillaries in the peri-ischemic area were no longer perfused at the 3- and 24-hour follow-up (45% [95% CI, 33%-58%] and 53% [95% CI, 39%-66%] reduction, respectively; <0.0001), which was associated with contraction of an equivalent proportion of peri-ischemic capillary pericytes. The capillaries in the peri-ischemic cortex that remained perfused showed increased point prevalence of dynamic flow stalling (0.5% [95% CI, 0.2%-0.7%] at baseline, 5.1% [95% CI, 3.2%-6.5%] and 3.2% [95% CI, 1.1%-5.3%] at 3- and 24-hour follow-up, respectively; =0.001). Whisker stimulation at the 3- and 24-hour follow-up led to reduced neurovascular coupling responses in the sensory cortex corresponding to the peri-ischemic region compared with that observed at baseline. Conclusions Arterial occlusion led to contraction of capillary pericytes and capillary flow stalling in the peri-ischemic cortex. Capillary dysfunction was associated with neurovascular uncoupling. Neurovascular coupling impairment associated with capillary dysfunction may be a mechanism that contributes to futile recanalization. Hence, the results from this study suggest a novel treatment target to improve neurological outcome after stroke.
Topics: Mice; Animals; Ischemic Stroke; Microcirculation; Brain; Stroke; Brain Ischemia; Arterial Occlusive Diseases; Cerebrovascular Circulation
PubMed: 37232244
DOI: 10.1161/JAHA.123.029527 -
Journal of Neurochemistry Jan 2022Stroke is a serious neurological disorder caused by blockage or rupture of cerebral blood vessels. Two main aims in acute stroke therapy include the restoration of...
Disturbed cerebral circulation and metabolism matters: A preface to the special issue "Stroke and Energy Metabolism": A preface to the special issue "Stroke and Energy Metabolism".
Stroke is a serious neurological disorder caused by blockage or rupture of cerebral blood vessels. Two main aims in acute stroke therapy include the restoration of cerebral blood flow in order to preserve energy supply to neurons and other brain cells, and minimizing neuronal loss. Maintenance of energy homeostasis in the brain drives neural network dynamics, which preserves normal brain function under physiological conditions. As such, cerebral energy homeostasis is a key target in stroke therapy. The various articles in this special issue highlight energy metabolism changes following stroke, including disturbed cerebral blood circulation, mitochondrial dysfunction, programmed neuronal cell death and cell-cell communication in brain metabolism. Collectively, this series of articles provides insight and presents new avenues for further research to improve the clinical management of stroke patients.
Topics: Animals; Brain; Cerebrovascular Circulation; Humans; Stroke
PubMed: 34894153
DOI: 10.1111/jnc.15552 -
Journal of Cardiovascular Magnetic... Apr 2016Arterial spin labeling (ASL) is a cardiovascular magnetic resonance (CMR) technique for mapping regional myocardial blood flow. It does not require any contrast agents,... (Review)
Review
Arterial spin labeling (ASL) is a cardiovascular magnetic resonance (CMR) technique for mapping regional myocardial blood flow. It does not require any contrast agents, is compatible with stress testing, and can be performed repeatedly or even continuously. ASL-CMR has been performed with great success in small-animals, but sensitivity to date has been poor in large animals and humans and remains an active area of research. This review paper summarizes the development of ASL-CMR techniques, current state-of-the-art imaging methods, the latest findings from pre-clinical and clinical studies, and future directions. We also explain how successful developments in brain ASL and small-animal ASL-CMR have helped to inform developments in large animal and human ASL-CMR.
Topics: Animals; Contrast Media; Coronary Circulation; Heart Diseases; Humans; Magnetic Resonance Imaging; Models, Animal; Myocardial Perfusion Imaging; Predictive Value of Tests; Prognosis; Regional Blood Flow; Spin Labels
PubMed: 27071861
DOI: 10.1186/s12968-016-0235-4