Non-uniform response of regional cerebral blood flow to stimulation of cervical sympathetic nerve

Regional cerebral blood flow (CBF) was measured by an autoradiographic method in nine adult cats, using antipyrine-¹⁴C as a diffusible indicator. In seven of the cats, CBF measurements were made during stimulation of a cervical sympathetic trunk. Stimulation caused minor regional decreases of CBF in at least five of these seven cats. The decreases were non-uniform and occurred almost exclusively in cortical structures. Although constriction of cervical arteries probably accounts for some of the effects of sympathetic stimulation, the present study indicates that there is also an effect on cerebral regulatory arterioles. However, there is no convincing evidence that function of the autonomic nervous system is necessary for the normal regulation of the cerebral circulation.     

Sustained cerebral vasoconstriction during bilateral sympathetic stimulation in anesthetized rabbits

Temporal aspects of bilateral sympathetic nerve stimulation on cerebral blood flow (CBF) were examined in anesthetized rabbits (n = 7). CBF ranged from 32 to 50 ml/min per 100 g. Bilateral stimulation reduced blood flow by 17-31% to cerebrum, diencephalon-mesencephalon and cerebellum, and responses were constant between 2 and 6 min of stimulation. Sustained cerebral vasoconstriction is consistent with an important role for sympathetic nerves in the regulation of CBF.     

Pial vascular behavior during bilateral and contralateral cervical sympathetic stimulation

The present study in cats investigates the effect of cervical sympathetic stimulation on changes of diameter of pial arteries and veins, CBF, and intracranial pressure (ICP) using the cranial window and hydrogen clearance techniques. During 20 min of bilateral stimulation, pial arteries maximally constricted by 12%, veins by 13-15%. While the constriction of the large arteries remained stable during the whole 20-min period of bilateral stimulation, small arteries escaped after some 2 min. A similar though weaker trend was noted for the veins. CBF was reduced at 2 min by 31%, and was not different from resting at 18 min. Contralateral stimulation for 20 min induced early constriction only in small arteries, while all other vessels remained more or less unreactive. This phenomenon is explained by interhemispheric arterial collaterals that bring sympathetic fibers mainly to small arteries contralaterally. ICP was lowered initially by 47 +/- 12% during bilateral and by 23 +/- 5% during contralateral stimulation. ICP escaped after 2 and 5 min during bilateral and contralateral stimulation, respectively, and even started to rise after some 10 min. From these data, it is concluded that the sympathoadrenergic system exerts a short-lasting protective effect upon cerebral vascular volume. Small arteries escape from constriction as a consequence of primarily myogenic counteraction of pial and intraparenchymal vessels, and probably additional metabolic dilatation of intraparenchymal vessels.     

Role of prostaglandins in modulating sympathetic vasoconstriction in the cerebral circulation in anesthetized rabbits

The effects of the interaction between sympathetic nerves and prostaglandins in the cerebral circulation were examined. The hypothesis tested was that inhibition of prostaglandin synthesis by indomethacin would potentiate decreases in CBF caused by sympathetic nerve stimulation. In anesthetized rabbits, following administration of either indomethacin (10 mg/kg) or vehicle, CBF was measured with 15-micron microspheres prior to stimulation and following 3-5 min of electrical stimulation (4, 8, 16 Hz) of both superior cervical ganglia. In the vehicle group, CBF was 33-42 ml/min/100 g prior to stimulation. Bilateral sympathetic stimulation reduced blood flow to the cerebrum by 12 +/- 6% (mean +/- SEM) (p less than 0.05) at 4 Hz (n = 8), by 20 +/- 4% (p less than 0.05) at 8 Hz (n = 12), and 21 +/- 6% (p less than 0.05) at 16 Hz (n = 11). In the indomethacin group, CBF was 37-48 ml/min/100 g prior to stimulation. Bilateral stimulation decreased blood flow to the cerebrum by 7 +/- 5% (NS) at 4 Hz (n = 8), by 25 +/- 3% (p less than 0.05) at 8 Hz (n = 6), and by 20 +/- 6% (NS) at 16 Hz (n = 6). Decreases in CBF during nerve stimulation were blocked by prazosin, an alpha-adrenergic antagonist. In additional experiments, cerebral vascular constrictor responses to hypocapnia were found to be similar in the vehicle and indomethacin groups. This study provides evidence that sympathetic nerves can decrease CBF substantially even at low stimulation frequencies. Further, results of this study indicate that prostaglandins do not attenuate the effects of sympathetic stimulation on the cerebral circulation.     

Brain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. prolonged effects at high and low levels of stimulation

PURPOSE: To measure vagus nerve stimulation (VNS)-induced cerebral blood flow (CBF) effects after prolonged VNS and to compare these effects with immediate VNS effects on CBF. METHODS: Ten consenting partial epilepsy patients had positron emission tomography (PET) with intravenous [15O]H2O. Each had three control scans without VNS and three scans during 30 s of VNS, within 20 h after VNS began (immediate-effect study), and repeated after 3 months of VNS (prolonged study). After intrasubject subtraction of control from stimulation scans, images were anatomically transformed for intersubject averaging and superimposed on magnetic resonance imaging (MRI) for anatomic localization. Changes on t-statistical maps were considered significant at p < 0.05 (corrected for multiple comparisons). RESULTS: During prolonged studies, CBF changes were not observed in any regions that did not have CBF changes during immediate-effect studies. During both types of studies, VNS-induced CBF increases were similarly located in the bilateral thalami, hypothalami, inferior cerebellar hemispheres, and right postcentral gyrus. During immediate-effect studies, VNS decreased bilateral hippocampal, amygdalar, and cingulate CBF and increased bilateral insular CBF; no significant CBF changes were observed in these regions during prolonged studies. Mean seizure frequency decreased by 25% over a 3-month period between immediate and prolonged PET studies, compared with 3 months before VNS began. CONCLUSIONS: Seizure control improved during a period over which some immediate VNS-induced CBF changes declined (mainly over cortical regions), whereas other VNS-induced CBF changes persisted (mainly over subcortical regions). Altered synaptic activities at sites of persisting VNS-induced CBF changes may reflect antiseizure actions.     

Umweltabhängigkeit der frühkindlichen zentralnervösen entwicklung: (Schriftenreihe aus dem gebiete des öffentlichen gesundheitswesens,vol. 34), by J. Pechstein,xii + 189 pages, 54 illustrations, 32 tables,Georg Thieme Verlag,Stuttgart, 1974, DM 18.50

Cerebral blood flow (CBF) was measured by a ¹³³Xe inhalation technique in 8 patients with chronic high spinal cord injuries. Six patients had a physiologically complete cervical cord transection and 1 subject had an incomplete C4–5 lesion but with evidence of interruption of sympathetic pathways. CBF and arterial blood pressure (BP) were measured in the supine position and then in the sitting, or feet up, position to produce a change of BP. In 4 patients CBF was measured during a suction manoeuvre applied to the lower half of the body to produce a fall of BP. There was no significant change of CBF in the patients during hypo- and hypertension. The response of CBF to hyperventilation for 5 min was measured in the supine position and did not differ significantly from that of 13 normal “control” subjects and 1 patient with a lesion at T2–3. It is concluded that the responses of the cerebral circulation to change of blood pressure and to hypocapnia are normal in patients with high spinal cord transection. The mechanisms involved in these responses are therefore independent of control via cervical sympathetic pathways.     

Role of sympathetic nervous system in activity-induced cerebral perfusion

Several studies have suggested that autonomic neural control plays a role in regulation of cerebral blood flow (CBF), although the exact role of the sympathetic nervous system on CBF remains debated. The effects of sympathetic innervation on activity-induced cerebral perfusion changes in humans have not been studied. The aims of this study were therefore (a) to investigate patients with an “intrinsic” sympathetic deficit after stroke and healthy controls with regard to activity-induced cerebral perfusion changes, and (b) to investigate possible differences in functional CBF regulation between the anterior and posterior circulation. Cerebral blood flow velocity in the medial cerebral artery (MCA) and posterior cerebral artery (PCA) was investigated in 21 healthy controls and 17 patients with Wallenberg’s syndrome using transcranial Doppler sonography during cortical activation of MCA and PCA territories, respectively. Patients with a central sympathetic deficit had a prolonged decrease of resistance in the MCA and showed a slower and less pronounced decrease of resistance in the PCA upon cortical activation. No difference was observed between the side with and without sympathetic deficit. Results suggest that (a) sympathetic efferents are involved in economisation of activity-induced changes of cerebral perfusion in the anterior circulation, (b) activity-induced sympathetic regulation of blood flow differs between the anterior and posterior vascular territories in humans and (c) a possible resting sympathetic tonus on extraparenchymal vessel might exist in the posterior circulation.     

Effect of locus coeruleus stimulation on regional cerebral oxygen consumption in the cat

Regional cerebral oxygen consumption was determined during stimulation of the intra-axial noradrenergic pathway to quantitate the metabolic effects of this manipulation on cerebral oxygen extraction, cerebral blood flow (CBF) and its regional distribution. Regional arterial and venous oxygen saturation were examined microspectrophotometrically. Regional CBF was examined using radioactively tagged microspheres (15 +/- 3 microns in diameter). Oxygen consumption was calculated as the regional product of CBF and oxygen extraction. Bipolar concentric electrodes were stereotaxically implanted bilaterally in the locus coeruleus of alpha-chloralose anesthetized, artificially respired adult mongrel cats. The control group was killed after hemodynamic and CBF measurements were taken. The experimental group was sacrificed after these same measurements were taken before and during 10 min of bilateral locus coeruleus stimulation. The cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic blood pressure was significantly increased during treatment. The heterogeneity of venous oxygen saturation was significantly reduced by stimulation. Average CBF and oxygen consumption were significantly decreased to 57% and 59% of control, respectively. Oxygen consumption was significantly reduced in the hypothalamus from 1.5 +/- 0.3 to 0.9 +/- 0.3 ml O2/min/100 g and from 3.5 +/- 0.9 to 1.2 +/- 0.4 ml O2/min/100 g in the cerebellum by treatment. Changes in the neuronal and/or synthetic cerebral activity produced regional decreases in cerebral oxygen consumption and secondarily altered CBF. These changes are probably due to interaction of the intraparenchymal noradrenergic pathways with other systems or processes in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noninvasive measurement of the cerebral blood flow response in human lateral geniculate nucleus with arterial spin labeling fMRI

To date, functional magnetic resonance imaging (fMRI) studies of the lateral geniculate nucleus (LGN) have primarily focused on measures of the blood oxygenation level dependent (BOLD) signal. Arterial spin labeling (ASL) is an MRI method that can provide direct measures of functional cerebral blood flow (CBF) changes. Because CBF is a well-defined physiological quantity that contributes to BOLD contrast, CBF measures can be used to improve the quantitative interpretation of fMRI studies. However, due in part to the low intrinsic signal-to-noise ratio of the ASL method, measures of functional CBF changes in the LGN are challenging and have not previously been reported. In this study, we demonstrate the feasibility of using ASL fMRI to measure the CBF response of the LGN to visual stimulation on a 3 T MRI system. The use of background suppression and physiological noise reduction techniques allowed reliable detection of LGN activation in all five subjects studied. The measured percent CBF response during activation ranged from 40 to 100%, assuming no interaction between the left and right LGN.     

Regional cerebral blood flow changes associated with ethanol intoxication

Regional cerebral blood flow (CBF) was measured via the 133Xenon inhalation technique in 26 healthy volunteers before and 60 minutes after the oral administration of ethyl alcohol or placebo on a double-blind basis. The cerebral blood flow values, corrected for test-retest differences in carbon dioxide showed a significant bilateral increase after ethanol administration. Blood levels of ethanol, estimated with a breath analyser, did not correlate with the CBF changes.     

Differential effects of intranasal insulin and caffeine on cerebral blood flow

Insulin is an important modulator of brain functions such as memory and appetite regulation. Besides the effect on neuronal activity, it is also possible that insulin has a direct vasodilatory effect on cerebral blood flow (CBF). We investigated the impact of increased insulin levels in the central nervous system on basal and task-induced CBF as well as blood oxygenation level-dependent (BOLD) response in the visual cortex using pulsed arterial spin-labeling MRI. An intranasal insulin application was used to avoid peripheral hyperinsulinaemia, which would lead to a cascade of hormonal changes. In a control experiment, caffeine was applied due to its well-known impact on the vasculature of the brain leading to a reliable reduction of CBF. Eight lean subjects were included in the study. On 2 separate days, intranasal human insulin or caffeine tablets were given to the subjects after fasting over night. On each day, basal CBF and task-induced CBF were measured before and 30 min after application of insulin or caffeine in each subject. During the task condition, a flickering checkerboard was presented. Insulin had no effect on basal CBF and task-induced CBF in comparison with drug-free baseline measurement in the visual cortex and control regions. After caffeine application, however, there was a significant decrease of CBF during stimulation in the visual cortex. The BOLD response was not altered by insulin or caffeine between pre- and postdose measurements. In conclusion, we found no evidence for a direct vasodilatory effect of intranasal insulin on the cerebral vascular system in this study.     

颈髓电刺激增加脑血流的作用机制研究

目的 尽管颈髓电刺激（SCS）在许多动物实验中已被证实能增加脑血流,但其作用机理还不甚明了。本文将从脑血管的交感和副交感通路方面探讨SCS对脑血流的影响机理。方法 对SD大鼠给予SCS并用激光多普勒（LDF）实时记录脑血流。动物分成5组,对照组：不对神经纤维和神经节作任何手术处理;V1组：切断双侧鼻睫状神经及其副交感节后纤维;SCS组：切断双侧颈上神经节;V1＋SCG：切断双侧鼻睫状神经及其副交感节后纤维及双侧颈上神经节;假手术组：手术暴露双侧鼻睫状神经和其副交感节后纤维及双侧颈上神经节,但不切断神经纤维或神经节。结果 SCS时的LDF变化在对照组、V1和SCG组间没有显著性差异。但在V1＋SCG组中,SCS的升脑血流效应却被明显抑制了。结论 SCS的升脑血流效应可能是通过交感和副交感双重通路实现的。     

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.     

Regional cerebral blood flow during hypotension in normotensive and stroke-prone spontaneously hypertensive rats: effect of sympathetic denervation

This study was performed to determine whether, in hypertensive and normotensive rats, chronic sympathetic denervation impairs cerebral vasodilator responses during hypotension, and to determine whether there are regional differences in the autoregulatory response of brain vessels during hypotension. The superior cervical ganglion was removed on one side in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive (WKY) rats. Cerebral blood flow (CBF) was measured with microspheres when the rats were 5-6 months old. Chronic sympathetic denervation had little or no effect on cerebral vasodilator responses during acute hypotension in SHRSP and WKY. We suggest that the increase in incidence of ischemic infarction that we have observed previously after chronic sympathetic denervation in SHRSP probably is not the result of ischemia during episodes of hypotension. We also observed major regional differences in the response of cerebral vessels during acute hypotension in SHRSP: blood flow to brainstem was preserved better than flow to cerebrum and cerebellum. Thus the "lower limit" of the autoregulatory plateau differs in various regions of the brain in SHRSP.     

Nonlinear temporal dynamics of the cerebral blood flow response

The linearity of the cerebral perfusion response relative to stimulus duration is an important consideration in the characterization of the relationship between regional cerebral blood flow (CBF), cerebral metabolism, and the blood oxygenation level dependent (BOLD) signal. It is also a critical component in the design and analysis of functional neuroimaging studies. To study the linearity of the CBF response to different duration stimuli, the perfusion response in primary motor and visual cortices was measured during stimulation using an arterial spin labeling technique with magnetic resonance imaging (MRI) that allows simultaneous measurement of CBF and BOLD changes. In each study, the perfusion response was measured for stimuli lasting 2, 6, and 18 sec. The CBF response was found in general to be nonlinearly related to stimulus duration, although the strength of nonlinearity varied between the motor and visual cortices. In contrast, the BOLD response was found to be strongly nonlinear in both regions studied, in agreement with previous findings. The observed nonlinearities are consistent with a model with a nonlinear step from stimulus to neural activity, a linear step from neural activity to CBF change, and a nonlinear step from CBF change to BOLD signal change.     

Cerebrovascular effects of sodium nitroprusside in the anaesthetized baboon: a positron emission tomographic study.

The effects of sodium nitroprusside (SNP), a potent hypotensive agent, on cerebral blood flow (CBF) have been extensively studied in clinical and experimental situations but the results remain controversial. Whereas its properties would predict a dilatation of cerebral blood vessels, most studies report either no change or a decrease in CBF. The aim of this study was to investigate the effects of SNP on CBF, cerebral blood volume (CBV), and cerebral oxygen metabolism (CMRO2), by means of positron emission tomography in the anaesthetized baboon. Measurements were performed during normotension (mean arterial pressure (MABP): 97+/-16 mm Hg) and repeated following SNP-induced hypotension (MABP: 44+/-9 mm Hg). Sodium nitroprusside led to an increase in CBF and CBV (+30% and +37%, respectively, P<0.05), whereas no change in CMRO2 was noted. Linear regression analysis of CBF values as a function of MABP confirmed that CBF increases when MABP is reduced by SNP. The comparison between these cerebrovascular changes and those found during trimetaphan-induced hypotension in our previously published studies further argues for a direct dilatatory effect of SNP on cerebral blood vessels.     

Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat.

In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated is not known. Alterations in several parameters may possibly explain the increase in CBF and the resetting of the relation between CBF and cerebral metabolism. To study this phenomenon further, we measured global CBF and global cerebral metabolism with the Kety-Schmidt technique in the wakeful rat before and during infusion of ketone bodies. During acute hyperketonemia (average concentration of beta-hydroxybutyrate: 6 mmol/L), global CBF increased 65% from 108 to 178 mL/100 g min and the cerebral metabolic rates for both oxygen and glucose remained constant. This resetting of the relation between CBF and cerebral metabolism could not be explained by alterations in blood pH or arterial CO2 tension. By measuring cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy, it could further be concluded that the brain pH was unchanged during acute hyperketonemia. These observations indicate that the mechanism responsible for the increase in CBF is rather a direct effect on the cerebral endothelium than via some metabolic interactions.     

Mechanisms of pain-induced local cerebral blood flow changes in the rat sensory cortex and thalamus

It is a well-known phenomenon that cerebral blood flow is coupled to neural activation induced by non-noxious somatosensory stimulation. However, basic questions related to pain-induced cerebral blood flow changes remain unanswered. In the present study, the sciatic nerve of anesthetized rats was subjected to electric stimulation with noxious and non-noxious parameters. Changes in local cerebral blood flow and neuronal activity were determined simultaneously in the sensory cortex and in the thalamus by laser-Doppler flowmetry and c-fos immunohistochemistry, respectively. The role of different vasoregulatory mechanisms and the pain-induced increase in mean arterial blood pressure (MABP) were examined with specific blocking agents and by means of rapid intra-arterial transfusion. Noxious stimulation resulted in significant enhancement of neuronal activity both in the thalamus and in the somatosensory cortex indicated by marked c-fos expression in these areas. Cortical and thalamic blood flow (cBF and tBF) increased by 47±4 and 44±3% during the stimulation while the MABP elevated by 35±2%. Similar changes in MABP induced by intra-arterial transfusion had no effect on tBF, while cBF increased only by 18±5%. Blockade of ATP sensitive potassium channels (K⁺_ATP) and sympathetic β-receptors significantly attenuated the pain-induced blood flow increases in both investigated areas, while inhibition of nitric oxide synthase was effective only in the thalamus. The blockade of the sympathetic -receptors, opiate receptors, and the cyclooxygenase enzyme had no effect on the pain-induced cerebral blood flow elevations. These findings demonstrate that during noxious stimulation, cerebral blood flow is adjusted to the increased neural activity by the interaction of vasoconstrictor autoregulatory and specific vasodilator mechanisms, involving the activation of sympathetic β-receptors, K⁺_ATP-channels and the release of nitric oxide.     

Correlation of middle latency auditory evoked potentials and cerebral blood flow changes

Abstract  The purpose of this study is to find the correlation between middle latency auditory evoked potentials (MLAEP) and sound activated single photon emission computed tomography (SPECT) studies. This study was performed on six normal right-handed volunteers with a mean age of 35.2 ± 7.6 years, using the split-dose technique. First, a SPECT study was performed on subjects in blinded, awake and silent states. After bilateral ears were stimulated with a click sound, MLAEP and a second SPECT study were performed. Subtraction of the first SPECT from the second SPECT revealed a statistically significant increase of cerebral blood flow (CBF) in the bilateral superior temporal region. Bilateral Na amplitudes of MLAEP had a statistically significant and good correlation with the percentages of CBF changes in the bilateral superior temporal region. The superior temporal cerebral blood flow activation can be expressed by electrophysiological activation. Moreover, correlation during the left Na components and left frontal and occipital lobe are discussed.     

Regional cerebral blood flow autoregulation in normotensive and spontaneously hypertensive rats--effects of sympathetic denervation

The present study was designed to investigate the effect of acute sympathetic denervation on the regional cerebral blood flow (CBF) autoregulation during acute elevation of blood pressure in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). CBF to the parietal cortex and thalamus was measured by the hydrogen clearance method and, to test autoregulation, systemic arterial blood pressure was elevated by intravenous infusion of phenylephrine. Superior cervical ganglia were removed on both sides to interrupt sympathetic innervation in the deeper structures of the brain. Acute bilateral sympathetic denervation did not alter the resting blood pressure or CBF in either SHR or WKY. In innervated SHR, resting mean arterial pressure (MAP) was 165 +/- 5 mm Hg (mean +/- SEM) and the upper limit of autoregulation in the cortex was 210 +/- 3 mm Hg, which was significantly lower than that in the thalamus (229 +/- 3 mm Hg, p less than 0.02). In bilaterally denervated SHR, the upper limits were lowered to 193 +/- 4 mm Hg in the cortex (p less than 0.02 vs. innervated SHR) and to 207 +/- 5 mm Hg in the thalamus (p less than 0.02 vs. innervated). In WKY, resting MAP was approximately 55 mm Hg lower than that in SHR. Acute denervation reduced the upper limits from 142 +/- 3 mm Hg to 130 +/- 4 in the cortex (p less than 0.05) and from 158 +/- 4 to 145 +/- 4 in the thalamus (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)