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Journal ArticleDOI

Cerebral Blood Flow During

01 Nov 1970-JAMA Neurology (American Medical Association)-Vol. 23, Iss: 5, pp 394-403
TL;DR: The pH hypothesis is physiologically attractive, but evidence against it comes from a series of experiments in several laboratories in which prolonged passive hyperventilation of animals and man producing sustained, constant arterial hypocapnia is produced.
Abstract: IT IS WELL established that the arterial carbon dioxide tension (Pco2) is an important factor controlling cerebral vascular resistance (CVR) and cerebral blood flow (CBF) in healthy animals and man. An acute rise in Pco2causes a decrease in CVR which increases the CBF, and a fall in Pco2has the opposite effect. However, during sustained alteration of Pco2, the CBF and absolute carbon dioxide tension often fail to correlate closely, and much recent evidence summarized by Lassen1suggests that alterations of the pH of the brain's extracellular space mediate the cerebral vascular response to carbon dioxide and that brain interstitial fluid pH is the major regulator of CBF. The pH hypothesis is physiologically attractive, but evidence against it comes from a series of experiments in several laboratories in which prolonged passive hyperventilation of animals2-5and man6producing sustained, constant arterial hypocapnia
Citations
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TL;DR: Neuroimaging, with its unique metabolic perspective, has alerted us to the ongoing and costly intrinsic activity within brain systems that most likely represents the largest fraction of the brain's functional activity.
Abstract: Functional brain imaging with positron emission tomography and magnetic resonance imaging has been used extensively to map regional changes in brain activity. The signal used by both techniques is based on changes in local circulation and metabolism (brain work). Our understanding of the cell biology of these changes has progressed greatly in the past decade. New insights have emerged on the role of astrocytes in signal transduction as has an appreciation of the unique contribution of aerobic glycolysis to brain energy metabolism. Likewise our understanding of the neurophysiologic processes responsible for imaging signals has progressed from an assumption that spiking activity (output) of neurons is most relevant to one focused on their input. Finally, neuroimaging, with its unique metabolic perspective, has alerted us to the ongoing and costly intrinsic activity within brain systems that most likely represents the largest fraction of the brain's functional activity.

1,495 citations

Journal ArticleDOI
01 Sep 1974-Stroke
TL;DR: The relationships between cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral vascular mean transit time (t®v) during acute changes in the PaCO2 over a range of 15 to 76 torr were investigated in vivo in rhesus monkeys by serially determining themean transit time of a vascular tracer, 15O-labeled carboxyhemoglobin, and the mean transitTime of a diffusible tracer
Abstract: The relationships between cerebral blood volume (CBV), cerebral blood flow (CBF), and the cerebral vascular mean transit time (t v ) during acute changes in the PaCO 2 over a range of 15 to 76 torr were investigated in vivo in rhesus monkeys by serially determining the mean transit time of a vascular tracer, 15 O-labeled carboxyhemoglobin, and the mean transit time of a diffusible tracer, 15 O-labeled water. Over this range of PaCO 2 , a significant linear relationship of CBV = 0.041 PaCO 2 + 2.0 was found. For each one torr change in PaCO 2 , there is a change in CBV of 0.041 ml/100 gm of perfused tissue. At a normocarbic value of PaCO 2 (37 torr), an average value of 3.5 ml/100 gm was found. A nonlinear relationship of CBV and CBF was found. This relationship is expressed in the equation, CBV = 0.80 CBF 0.38 . A significant linear relationship was found between CBF and PaCO 2 . This was described by the equation, CBF = 1.8 PaCO 2 - 16.75. For each one torr change in the PaCO 2 , there is a 1.8 ml/100 gm per minute change in the CBF. At a normocarbic value of PaCO 2 (37 torr), an average value of CBF of 50 ml/100 gm per minute was found. The relationship of CBV and t v was nonlinear and was expressed in the equation, t C15O = 41 CBF -0.62 .

1,021 citations

Journal ArticleDOI
TL;DR: It is argued that the alternative possibility that brain functions are mainly intrinsic, involving information processing for interpreting, responding to and predicting environmental demands best captures the essence of brain function.

890 citations

Journal ArticleDOI
TL;DR: Hyperemia was found at all age levels (15 to 85 years), and there was a highly significant association between hyperemia and the occurrence of intracranial hypertension, defined as an intrusion above 20 mm Hg.
Abstract: ✓ Cerebral blood flow (CBF) measurements were made in 75 adult patients with closed head injuries (mean Glasgow Coma Scale score 6.2), using the xenon-133 intravenous injection method with eight detectors over each hemisphere. All patients were studied acutely within 96 hours of trauma, and repeatedly observed until death or recovery (total of 361 examinations). Arteriojugular venous oxygen differences (AVDO2) were obtained in 55 of the patients, which permitted assessment of the balance between metabolism and blood flow, and provided estimates of cerebral metabolic rate for oxygen (CMRO2). Based on mean regional CBF, the patients were classified into two groups: those who exhibited hyperemia on one or more examinations, and those who had a consistently reduced flow during their acute illness. “Hyperemia” was defined as a normal or supernormal CBF in the presence of coma, a definition that was independently confirmed by narrow AVDO2's indicative of “luxury perfusion.” During coma, all patients showed a si...

786 citations

Journal ArticleDOI
TL;DR: Striking regional variations in aerobic glycolysis in the normal human brain provide an opportunity to explore how brain systems differentially use the diverse cell biology of glucose in support of their functional specializations in health and disease.
Abstract: Aerobic glycolysis is defined as glucose utilization in excess of that used for oxidative phosphorylation despite sufficient oxygen to completely metabolize glucose to carbon dioxide and water. Aerobic glycolysis is present in the normal human brain at rest and increases locally during increased neuronal activity; yet its many biological functions have received scant attention because of a prevailing energy-centric focus on the role of glucose as substrate for oxidative phosphorylation. As an initial step in redressing this neglect, we measured the regional distribution of aerobic glycolysis with positron emission tomography in 33 neurologically normal young adults at rest. We show that the distribution of aerobic glycolysis in the brain is differentially present in previously well-described functional areas. In particular, aerobic glycolysis is significantly elevated in medial and lateral parietal and prefrontal cortices. In contrast, the cerebellum and medial temporal lobes have levels of aerobic glycolysis significantly below the brain mean. The levels of aerobic glycolysis are not strictly related to the levels of brain energy metabolism. For example, sensory cortices exhibit high metabolic rates for glucose and oxygen consumption but low rates of aerobic glycolysis. These striking regional variations in aerobic glycolysis in the normal human brain provide an opportunity to explore how brain systems differentially use the diverse cell biology of glucose in support of their functional specializations in health and disease.

565 citations

References
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Journal ArticleDOI
TL;DR: Evidence bearing on the intrinsic control of the human cerebral circulation as revealed by quantitative measurements is derived.
Abstract: A method for measuring quantitatively the volume of cerebral blood flow in man by inhalation of nitrous oxide (1) found its first application in a study of the cerebral circulatory effects of low CO2 tension achieved by hyperventilation; of high CO2 tension, and of high and low 02 tensions obtained by inhalation of appropriate gas mixtures (2). Only the first part of this study, the effects of active and passive hyperventilation, has been published in detail (3). The purpose of the present paper is to present the remainder of these findings and to derive from them, together with those of the hyperventilation experiments, evidence bearing on the intrinsic control of the human cerebral circulation as revealed by quantitative measurements.

1,768 citations

Journal ArticleDOI
TL;DR: The effect of arterial Pco2 in the control of cerebral hemodynamics over the full range of responsiveness of the cerebral vasculature was studied in the rhesus monkey.
Abstract: The effect of arterial Pco2 in the control of cerebral hemodynamics over the full range of responsiveness of the cerebral vasculature was studied in the rhesus monkey. Cerebral perfusion pressure a...

538 citations

Journal ArticleDOI
TL;DR: Cerebral blood flow appears to return to normal at the prevailing Paco2, probably because the pH of cerebrospinal fluid and of the extracellular fluid of cerebral vascular smooth muscle is kept normal by active transport across the ‘blood-brain’ barrier.
Abstract: Cerebral blood flow was determined by an N2O method in 7 normal men at sea level and after 6 to 12 hr and 3 to 5 days at 3810 m altitude. An infrared N2O analyzer was used both to measure end-tidal PN2O so that it could be kept constant for 15 min and to determine blood N2O, for which a simple gas extraction method was devised. In addition, acute changes in cerebral blood flow were estimated from cerebral A-V O2 differences. Control cerebral blood flow was 43 ml per 100 g per min; it increased 24% at 6 to 12 hours and 13% at 3 to 5 days at altitude. After 3 to 5 days, pH of cerebrospinal fluid was normal (7.31) in four subjects while arterial blood pH was alkaline (7.47); arterial blood Pco2 had fallen from 41 to 30 mm Hg. Acute correction of hypoxia restored cerebral blood flow to control while mean Pco2 was still 31 mm Hg. Addition of O2 and CO2 to inspired air raised cerebral blood flow 34% above control at Pao2 = 170, Paco2 = 35 mm Hg. Values obtained by extrapolation suggest that if arterial Pco2 was...

272 citations