Endorphinergic mechanisms in cerebral blood flow autoregulation

The influence of naturally occurring opioid peptides (Met-enkephalin (Met-Enk), dynorphin (DYN), β-endorphin (β-EP)) as well as morphine and the opiate antagonist naloxone and specific antisera on cerebral blood flow autoregulation was studied in anesthetized, artificially ventillated rats. Local hypothalamic blood flow (CBF, H₂-gas clearance technique) and total cerebral blood volume (CBV, photoelectric method) were simultaneously recorded. Autoregulation was tested by determining CBF and CBV during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Resting CBF decreased following Met-Enk, DYN, β-EP or morphine administration without simultaneous changes in CBV. Naloxone administration, on the contrary, increased CBV without affecting local CBF. Autoregulation of cerebral blood flow was maintained until 80 mm Hg, but not completely at 60 and 40 mm Hg arterial pressure in the control group. General opiate receptor blockade by 1 mg/kg s.c. naloxone abolished autoregulation at all levels, since CBF and CBV passively followed the arterial pressure changes. Intracerebroventricularly injected naloxone (1 μg/kg) as well as a specific antiserum against β-EP, but not against Met-Enk or DYN, resulted in the very same effect as peripherally injected naloxone. The present findings suggest that central, periventricular β-endorphinergic mechanisms might play a major role in CBF autoregulation.     

Anxiety and cerebral blood flow

The relationship between anxiety and cerebral blood flow (CBF) is of considerable clinical and research significance. Although a considerable amount of information is available on mechanisms through which anxiety may influence CBF, this topic has not received much attention in psychiatry. Earlier techniques for the measurement of CBF were cumbersome and invasive. With the advent of noninvasive techniques, study of CBF in psychiatric disorders, including anxiety, became easier, and a number of such studies have been conducted. In this article the literature on psychophysiological and clinical aspects of changes in CBF associated with anxiety is reviewed.     

Quantitative measurement of cerebral blood flow and cerebral blood volume after cerebral ischaemia

CBF obtained by the hydrogen clearance technique and cerebral blood volume (CBV) calculated from the [14C]dextran space were measured in three groups of rats subjected to temporary four-vessel occlusion to produce 15 min of ischaemia, followed by 60 min of reperfusion. In the control animals, mean CBF was 93 +/- 6 ml 100 g-1 min-1, which fell to 5.5 +/- 0.5 ml 100 g-1 min-1 during ischaemia. There was a marked early postischaemic hyperaemia (262 +/- 18 ml 100 g-1 min-1), but 1 h after the onset of ischaemia, there was a significant hypoperfusion (51 +/- 3 ml 100 g-1 min-1). Mean cortical dextran space was 1.58 +/- 0.09 ml 100 g-1 prior to ischaemia. Early in reperfusion there was a significant increase in CBV (1.85 +/- 0.24 ml 100 g-1) with a decrease during the period of hypoperfusion (1.33 +/- 0.03 ml 100 g-1). Therefore, following a period of temporary ischaemia, there are commensurate changes in CBF and CBV, and alterations in the permeability-surface area product at this time may be due to variations in surface area and not necessarily permeability.     

Regional cerebral blood flow in children--normal value and regional distribution of cerebral blood flow in childhood

The changes in CBF and rCBF through the entire age range include the rapid period in childhood was reported. Sixteen children between the ages of 1 and 15 and 14 adults were studied. These 30 subjects were either volunteers of out-patients without CT and EEG abnormalities. rCBF was measured by the 133Xe intravenous injection method using Varmet rCBF analyzer. Ther relationship between age and CBF, the correlation coefficient was calculated based on the regression equations and the regression curve with the highest correlation was chosen. For the analysis of rCBF, he mean rCBF values (ISI) of 3 channels corresponding to the frontal, temporal, parietal and occipital lobes were expressed as a percentage of the hemispheric CBF. The hemispheric blood flow (ISI and CBF gray) of children less than 5 years of age was approximately twice that found in adults. This value decreased rapidly with age and in the 10-15 years the blood flow was approximately 1.3-fold that of adults. Thereafter, there was a slow decrease and a negative correlation with age was found. The decrease showed the correlation on the following equations; y = 146.5 - 58.5 log x. (r = -0.903) for ISI and log y = 2.26 - 0.29 log x. (r = -0.881) for CBF gray, which was statistically significant. In contrast, the CBF white showed a slightly higher value in the 1-2 years old children, but thereafter the CBF did not show a notable decreases with age. Through the entire age range, a best fit for the Fw values was found with : y = 18.3 + 37.5/x. (r = 0.798), which was also statistically significant.     

Neurogenic control of cerebral blood flow

In experiments on 15 isolated dog brains, cerebral blood flow could be influenced by short (20 sec) supramaximal, unilateral electrical stimulation of the vagoysympathetic trunk, the trigeminal nerve and the medulla oblongata. The changes in cerebral vascular resistance and cerebral oxygen consumption developed 2 sec after onset of the stimulation, reaching their peak 30 sec later and lasted up to 3 min. During sympathetic stimulation cerebral blood flow decreased from 47.2 ml to $\text{42.0 ml}\text{100 g}$ tissue/min and cerebral vascular resistance increased about 18%. This constrictor effect was completely blocked by phentolamine. During vagal stimulation no effect could be observed. During trigeminal stimulation cerebral blood flow increased from 44.0 ml to $\text{48.9 ml}\text{100 g}$ tissue/min, cerebral vascular resistance decreased about 19%, and cerebral oxygen consumption increased about 12%. Reliable inhibition of this dilating response was not achieved with either propranolol or atropine and it is assumed that there are no vasodilator fibers in the trigeminal nerve. During medullary stimulation cerebral blood flow increased from 42.0 ml to $\text{54.7 ml}\text{100 g}$ tissue/min, cerebral vascular resistance decreased about 45% and cerebral oxygen consumption increased about 23%. The diminishing effects of propranolol and atropine on this dilating response was not statistically significant. A restricted region in the medulla is presented from which changes in cerebral blood flow produced by electrical stimulation were not associated with changes in the electrical pattern of the brain. Observations that the vascular and functional reactions of the brain can be dissociated point to a role of the medulla in regulating cerebral blood flow, but do not elucidate the mechanism. In general, the results support evidence that a double—metabolic and neurogenic—mechanism is involved in the control of cerebral blood flow. It is suggested that the effects during vagosympathetic stimulation are completely neurogenic, the effects during trigeminal stimulation mainly metabolic, and the effects during medullary stimulation both metabolic and neurogenic in origin.     

Regional cerebral blood flow in depression

Regional cerebral blood flow (rCBF) was measured in patients with endogenous depression by the single photon emission computed tomography (SPECT) using N-isopropyl-p-[123I]iodoamphetamine (IMP). The subjects were 32 patients with endogenous depression and 20 normal controls. These 32 patients, who were divided into 10 unmedicated group and 22 medicated group, were reexamined when the depressed patients reverted to a euthymic state (remission). The value of rCBF was assessed by the corticocerebellar ratio (CCR), which was expressed as a ratio of activity per pixel in the cerebral regions of interests (ROIs) to the activity per pixel in the cerebellum. The depressive patients showed a decrease in rCBF all over the cerebral regions and, especially, the lower rCBF in the left than in the right hemisphere. These changes turned toward normal in a remitted state following treatments, though there was no significant difference in rCBF between the medicated and unmedicated patients. There was a significantly negative correlation between the severity of depressive symptoms and the mean rCBF in a total of patients with depression. These results suggest that psychiatric symptoms in the depressive patients might be related to the left hemispheric dysfunction.     

Regional cerebral blood flow in neuropsychology

Measurements of regional cerebral blood flow (rCBF) provide information about the metabolic and functional level of the cortex. Different techniques for measurement of rCBF are described and their potentials and limitations are outlined. Typical results from measurements in normals during performance of mental tasks are shown and as well as clinical measurements in patients with organic dementia. Future improvements of the techniques regarding spatial as well as temporal resolution are outlined. It is concluded that measurements of rCBF are likely to be of great value in the future exploration of brain-behaviour relationships.     

Substance abuse and cerebral blood flow

OBJECTIVE AND METHOD: This paper reviews acute and chronic effects of drugs of abuse on cerebral blood flow (CBF) and metabolism and their clinical significance. The most important source of information for the review is human research reports published in refereed journals. A few animal studies, book chapters, and abstracts that are especially relevant are also included. RESULTS: In humans, ethanol in small doses produces cerebral vasodilation; higher doses induce cerebral vasoconstriction. Chronic alcoholism is associated with reduced CBF and cerebral metabolism. Sedatives and antianxiety drugs lead to global reduction in CBF and cerebral metabolism. Caffeine, even in small doses, is a potent cerebral vasoconstrictor. Cerebral vasodilation is seen immediately after cigarette smoking, but chronic smokers show global reduction in CBF. Changes in CBF after marijuana smoking are variable; both increases and decreases are seen. Chronic marijuana smoking, however, seems to reduce CBF. Most inhalants and solvents are vasodilators; chronic abuse is accompanied by a decrease in CBF. A number of drugs of abuse, including ethanol, amphetamines, cocaine, nicotine, and caffeine-phenylpropanolamine combinations, increase the risk for stroke. Reduction in CBF associated with chronic use of ethanol, nicotine, inhalants, and solvents is at least partially reversible upon abstinence. CONCLUSIONS: Topics for future research include regional brain function, which mediates drug-induced mood changes (euphoria); CBF concomitants of psychological and physiological characteristics that increase addiction potential; changes in CBF that accompany withdrawal syndromes; mechanisms responsible for drug-induced stroke; and effects of functional and organic complications on CBF.