Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation

Abstract

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: 1) autoregulation, which describes the response of the cerebrovasculature to changes in perfusion pressure, 2) vascular reactivity to vasoactive stimuli [including carbon dioxide (CO2)], 3) neurovascular coupling (NVC), i.e., the CBF response to local changes in neural activity (often standardized cognitive stimuli in humans), and 4) 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 CO2 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 inter-relationships 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.

The Effect of Data Length on the Assessment of Dynamic Cerebral Autoregulation with Transfer Function Analysis in Neurological ICU Patients

“…In neurological intensive care conditions, CA plays an important role in safeguarding adequate cerebral perfusion and reducing the risk of secondary brain injury. Moreover, the key role of BP control in the management of neurocritical care and the concept of optimal BP make the assessment of CA increasingly clinically important [ 15 ]. However, patients in the neurological intensive care unit (neuro-ICU) are notably different from those in the general population [ 15 ], and obtaining stable TFA parameters is relatively difficult under such conditions.…”

“…Moreover, the key role of BP control in the management of neurocritical care and the concept of optimal BP make the assessment of CA increasingly clinically important [ 15 ]. However, patients in the neurological intensive care unit (neuro-ICU) are notably different from those in the general population [ 15 ], and obtaining stable TFA parameters is relatively difficult under such conditions. For example, they are vulnerable to motion artifacts because of poor cooperation and clinical procedures.…”

The new frontier in pure autonomic failure: getting a grip on cerebral blood flow

“…Rather, these symptoms are directly determined by changes in cerebral blood flow (CBF) and oxygen delivery to the brain. While it is undisputed that the large and sudden changes in BP in PAF are the main driver of these changes in CBF, mechanisms such as cerebral autoregulation mediate the relationship between BP and CBF [2]. This means that if, for the same change in BP, some patients experience more symptoms than others, this difference may be explained by how effective autoregulation is at restoring CBF [2].…”

“…While it is undisputed that the large and sudden changes in BP in PAF are the main driver of these changes in CBF, mechanisms such as cerebral autoregulation mediate the relationship between BP and CBF [2]. This means that if, for the same change in BP, some patients experience more symptoms than others, this difference may be explained by how effective autoregulation is at restoring CBF [2]. With this in mind, it would make sense to measure changes in CBF, and not only in BP, in patients with PAF and other disorders characterized by efferent baroreflex failure (i.e., neurogenic orthostatic hypotension and supine hypertension).…”

“…In other words, in addition to the well-characterized peripheral changes, impairing systemic arterial vasoconstriction, the increase in CBF may be mediated by impaired sympathetic autonomic vasoconstriction. Although the autonomic nervous system has only limited direct innervation to cerebral blood vessels (only the proximal large vessels), and is thought to have a minor role in autoregulation, most work suggests that sympathetic cerebral vasoconstriction may protect against hyperperfusion in acute bouts of hypertension [2]. Thus, autonomic failure may reduce the cerebrovascular protection against the sudden large increase in BP from standing to supine in a PAF patient, causing a rise in CBF.…”