CBF Changes Research Articles

Regional Cerebral Blood Flow and Cerebrovascular Reactivity in IDDM

To investigate both rCBF and cerebrovascular reactivity, evaluated as pre- and post-ACZ rCBF differences in a group of IDDM patients with differences in duration of disease and severity of complications. rCBF was measured by the 133Xenon inhalation method in 20 IDDM patients and in 15 healthy control subjects before and after an intravenous injection of ACZ, a carbonic anhydrase inhibitor commonly used to assess cerebrovascular reactivity. Basal global CBF (the mean of 32 regional values) was within the normal range in all patients but 1, who showed slight hyperperfusion; moreover, in 3 patients with long-lasting disease, some hypoperfused regions were found. ANOVA showed an inverse correlation between basal global CBF (P < 0.01) and duration of diabetes, but no correlation with Hb, MABP, serum glucose concentration, or GHb. Compared with control subjects, the percentage of global CBF increment after ACZ administration was significantly impaired in 4 patients and gave a borderline response in 2 patients; 4 of these poor ACZ responders had retinopathy, and 1 had suffered from a TIA. Duration of diabetes, Hb, MABP, serum glucose concentration, and GHb did not correlate with the percentage of post-ACZ global CBF changes, and did not differ among the 6 poor ACZ responders and the other diabetic patients or control subjects. These results confirm that global CBF is within the normal range in most IDDM patients, although it is significantly influenced by the duration of diabetes; pathophysiological correlates of the altered cerebrovascular reactivity need to be further investigated. rCBF measurements, before and after ACZ administration, seem to represent a safe and reliable tool for assessing cerebrovascular function in IDDM.

Types of Traumatic Brain Injury and Regional Cerebral Blood Flow Assessed by &lt;SUP&gt;99m&lt;/SUP&gt;Tc-HMPAO SPECT

To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

Optical access to the brain: how artificial are cranial window techniques?

Observation of brain surface vessels through a cranial window, implanted into the skull of anesthetized animals, is a standard technique for investigation of the cerebral circulation. It has been suggested that changes in pial vascular diameter in response to vasoactive stimuli are qualitatively similar to those of the cerebral circulation as a whole and that changes in cerebral blood flow may be estimated from the reaction of pial vessels (Rosenblum and Kontos, 1974). The assumption, however, that intraparenchymal vessels repond as pial vessels do, has not been proven. In addition, large cerebral arteries may dilate while pial arterioles constrict, thereby preventing a cerebral blood flow response (Faraci and Heistad, 1990). Pial arteriolar diameter reactivity is not predictive of CBF changes, therefore. The technique, however, is most valuable in the investigation of the mechanisms of arteriolar reactivity in the brain.

Propofol-Induced Changes in CBF are Related to EEG Slowing, Not To Systemic Hypotension

Propofol-Induced Changes in CBF are Related to EEG Slowing, Not To Systemic Hypotension

Regional cerebral blood flow after marijuana smoking.

Regional CBF was measured with the 133Xe inhalation technique before and thrice after smoking marijuana of two strengths and placebo in 20 physically and mentally healthy male volunteers with a previous history of exposure to marijuana. They were drug-free at the time of the study. Blood pressure, pulse rate, end-tidal carbon dioxide, end-tidal carbon monoxide, and forehead skin perfusion were quantified during the CBF measurements. Blood samples were drawn for quantification of plasma levels of delta 9-tetrahydrocannabinol (THC) before and during the 2 h after smoking marijuana or placebo. Drug-induced intoxication and changes in mood were quantified with rating scales. Marijuana smoking was associated with bilateral CBF increase, which was maximal 30 min later. Greater CBF increases were seen in the frontal region and right hemisphere. No significant CBF changes were seen after placebo. Pulse rate and respiration increased significantly after marijuana but not placebo. Both marijuana and placebo smoking were associated with increased end-tidal carbon monoxide. CBF increase in both hemispheres correlated significantly with degree of intoxication, plasma levels of THC, and pulse rate.

Vibration-induced regional cerebral blood flow responses in normal aging.

Task-induced changes in regional CBF (rCBF) can be measured with positron emission tomography (PET) and provide a powerful tool to map brain function. Many studies using these techniques have investigated responses in healthy young subjects. Since many pathological conditions occur more commonly in older subjects, it is necessary to compare blood flow responses in these patients with appropriately age-matched controls. Furthermore, the effects of normal aging on such blood flow responses remain unknown. For both reasons, we designed this study to determine whether vibration-induced CBF responses change with advancing age in normals. CBF was measured with PET and bolus-administered H2(15)O in 26 subjects from 20 to 72 years old (mean = 39; SD = 19). Regional responses were identified by subtraction-image analysis. Left and right hand vibration produced consistent responses in contralateral primary sensorimotor area (PSA) and supplementary motor area (SMA). Response magnitudes were compared to age by linear regression. There were no substantial relationships between age and responses to vibration for PSA or SMA (PSA r = -0.28, p = 0.054; SMA r = -0.33, p = 0.13). Power analysis demonstrates a high degree of confidence (99.7% for PSA and 87% for SMA) for detecting at least a moderate correlation (r = 0.6) between response magnitude and age. We conclude that the rCBF responses to vibrotactile hand stimulation do not change with normal aging.

Effect of 2-chloroadenosine on cerebrovascular reactivity to hypercapnia in newborn pig.

The effect of local administration of vasodilative concentrations of the adenosine receptor agonist 2-chloroadenosine (2-CADO) on the hyperemic responses of the pial and parenchymal microcirculations to graded hypercapnia was determined. The cranial window and brain microdialysis-hydrogen clearance techniques were utilized in two groups of isoflurane-anesthetized newborn pigs to measure changes in pial diameters and local CBF, respectively, in response to graded hypercapnia in the absence and presence of 2-CADO. Progressive size-dependent dilations of pial arterioles [small = 41 +/- 7 microns (mean +/- SD), intermediate = 78 +/- 13 microns, and large = 176 +/- 57 microns in diameter] occurred in response to graded hypercapnia alone (PaCO2 = 58 and 98 mm Hg) and to superfusions of 2-CADO (10(-5) M) during normocapnia; the magnitude of the dilative response to each of these stimuli was inversely proportional to vessel size. When hypercapnia was induced concomitantly with 2-CADO superfusion, the dilative effects of each stimulus were directly additive. Similarly, local microdialysis infusion of 10(-5) M 2-CADO, which doubled CBF during normocapnia, did not affect the hyperemic response of the parenchymal circulation to graded hypercapnia (PaCO2 = 69 and 101 mm Hg). Our findings are consistent with the participation of adenosine in the mediation of cerebral hypercapnic hyperemia. If, however, adenosine is not involved in this dilative response, our results indicate that concomitant vascular and neuromodulatory actions induced by adenosine receptor stimulation do not affect the mechanism responsible for the hypercapnic hyperemic response.

Changes in neuropeptide Y after experimental traumatic brain injury in the rat.

We utilized a model of fluid percussion (FP) brain injury in the rat to examine the hypothesis that alterations in brain neuropeptide Y (NPY) concentrations occur following brain injury. Male rats (n = 44) were subjected to FP traumatic brain injury. One group of animals (n = 38) was killed at 1 min, 15 min, 1 h, or 24 h after brain injury, and regional brain homogenates were analyzed for NPY concentrations using radioimmunoassay. A second group of animals (n = 6) was killed for NPY immunocytochemistry. Concentrations of NPY in the injured left parietal cortex were significantly elevated at 15 min post injury (p less than 0.05). No changes were observed in other brain regions. NPY-immunoreactive fibers were seen at 15 min post injury predominantly in the injured cortex and adjacent hippocampus. These temporal changes in NPY immunoreactivity, together with previous observations concerning posttraumatic changes in regional CBF in these same areas, suggest that an increase in region NPY concentrations after brain injury may be involved in part in the pathogenesis of posttraumatic hypoperfusion.

CBF and cognitive evaluation of Alzheimer type patients before and after IMAO-B treatment: a pilot study

Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type, with a mild to moderate cognitive and behavioral impairment, were studied in a double blind design when taking for 60 days 5 mg twice a day of L-deprenyl or placebp. Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory, attention, and language efficiency measures and by SPECT- 99TcHMPAO procedure. Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency. At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF, while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF.

CBF changes during CCK-4-panic in normals : C. Benkelfat, J. Bradwejn, E. Meyer, M. Ellenbogen, S. Milot, A. Gjedde, A. Evans McGill University, Montreal, Canada

CBF changes during CCK-4-panic in normals : C. Benkelfat, J. Bradwejn, E. Meyer, M. Ellenbogen, S. Milot, A. Gjedde, A. Evans McGill University, Montreal, Canada

Attention and sentence processing deficits in Parkinson's disease: the role of anterior cingulate cortex.

Parkinson's disease (PD) is a complex neurodegenerative condition involving a motor disorder that is related to reduced dopaminergic input to the striatum. Intellectual deficits are also seen in PD, but the pathophysiology of these difficulties is poorly understood. Regional cerebral blood flow (rCBF) was studied in neurologically intact subjects during the performance of attention-demanding, sentence processing tasks using positron emission tomography (PET). The results demonstrated significantly increased rCBF in a distributed set of cerebral regions during the detection of an adjective or a particular agent in a sentence, including anterior cingulate cortex, left inferior and middle frontal cortex, left inferior temporo-occipital cortex, posterolateral temporal cortex, left caudate, and left thalamus. We identified defects in this cerebral network by studying PD patients with two PET techniques. Resting PET studies revealed a significant correlation between regional cerebral glucose metabolism in anterior cingulate cortex and deficits in attending to subtle grammatical aspects of sentences. Studies of PD patients with the PET activation technique revealed little change in anterior cingulate and left frontal CBF during performance of the adjective detection or agent detection tasks. These data suggest that a defect in anterior cingulate cortex contributes to the cognitive impairments observed in PD.

Reduction in focal cerebral ischemia by agents acting at imidazole receptors.

Treatment with the alpha 2-adrenergic antagonist idazoxan (IDA) can provide protection from global cerebral ischemia. However, IDA also recognizes another class of receptors, termed imidazole (IM) receptors, which differ from alpha 2-adrenergic receptors and are responsible for the hypotensive actions of some centrally acting agents such as the oxazole rilmenidine (RIL). We therefore sought to determine whether RIL, an agent highly selective for IM receptors, offered protection from focal cerebral ischemia elicited in rat by ligation of the middle cerebral artery (MCA). We compared the effects of RIL with the effects of IDA and the selective non-IM alpha 2-antagonist SKF 86466 (SKF). In addition, we examined whether the neuroprotective effects of RIL and IDA could be attributed to changes in local CBF (LCBF). The MCA was occluded and animals either received immediate administration of drug while arterial pressure was maintained for 1 h or had local CBF increased to 200% of control for 1 h by hypercapnia or hypertension. RIL elicited a significant dose-dependent preservation of tissue to 33% of control at optimal dose (0.75 mg/kg). IDA (3 mg/kg) significantly reduced the size of ischemic infarction by 22%. In contrast, SKF (15 mg/kg) as well as doubling of LCBF did not preserve ischemic tissue. We conclude that both RIL and IDA can reduce focal ischemic infarction but that the mechanism does not appear secondary to antagonism of alpha 2-adrenergic receptors or elevation of LCBF. Occupation of IM receptors, either in the ischemic zone or at remote brain sites, may be responsible for neuroprotection of RIL and IDA.

The Effects of a Competitive NMDA Receptor Antagonist (CGS-19755) on Cerebral Blood Flow and pH in Focal Ischemia

We report the effects of intravenous infusion of CGS-19755, a potent competitive N-methyl-D-aspartate (NMDA) antagonist, on local cerebral pH (LCpH) and local CBF (LCBF) in rats with occluded left middle cerebral and common carotid arteries. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique 4 h after vascular occlusion in three groups: no treatment, carrier infused, and a group receiving CGS-19755 at 10 mg/kg bolus immediately after occlusion followed by infusion at 5 mg kg-1 h-1 for 4 h. Compared with rats receiving carrier, several cortical structures on the side of occlusions showed significantly higher CBF in rats receiving CGS-19755. This drug also corrected the pH in several left cortical structures to values significantly higher than in the rats receiving carrier. The correction in LCpH was not limited to those regions showing significant elevations in LCBF. In the nonoccluded hemisphere, CGS-19755 significantly increased the hemispheric mean blood flow from 122 +/- 17 to 221 +/- 64 ml 100 g-1 min-1 (mean +/- SD of all structures, p less than 0.01) without any changes in LCpH. Cortical but not basal ganglia infarct volume was significantly smaller in rats receiving CGS-19755 than in the carrier-treated group. These results suggest that, at least partially, the neuroprotective effect of CGS-19755 in ischemia may be related to changes in CBF and pH in addition to its antagonist effect on the NMDA receptor.

Alterations of local cerebral blood flow and glucose uptake by electroconvulsive shock in rats

The effects of single and repeated electroconvulsive shock (ECS) treatments on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind-brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given “ceiling” keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF.

The acute effect of nimodipine on cerebral blood flow, its CO2 reactivity, and cerebral oxygen metabolism in human volunteers

The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO2 reactivity, and CMRO2. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO2 reactivity tests changes in CBF were estimated by the arterio-venous-oxygen-difference method. Median CBF was 52 ml/100 g/min (48-53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92-99). MABP was slightly reduced, by 8 mmHg (7-9), and 9 mmHg (4-11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO2, revealed a slight increase after 4 hours (p = 0.08). CMRO2 was 3.5 ml/100g/min (3.2-3.5) and was not changed by the infusion of NIM. At arterial CO2 tensions ranging from 4.0 to 6.5 Kpa the CO2 reactivity was 3.0% CBF/0.1 kPa (2.6-3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8-3.2) after the infusion of NIM for 3 hours (p = 0.02). The median slope of the LnCBFsat/PaCO2 relationship was 1.5 at baseline compared to 1.3 after NIM (p less than 0.01). No side effects were observed. The present study shows a decreased CO2 of the cerebral vessels and a maintained coupling of CBF and CMRO2 during the infusion of nimodipine.

Spinal cord stimulation and cerebral haemodynamics

An increase of regional cerebral blood flow (rCBF) has been shown to occur in man during spinal cord stimulation (SCS) by Hosobuchi (1986) and by Meglio et al. (1988) using the 133-Xenon wash-out technique. In this paper we report the effects of SCS on CBF as measured by two different techniques: 8 patients were studied with the 133-Xe method and 28 with the transcranial doppler sonography (TCD), in two cases both studies were performed. The aim of our study was to: 1-verify the effect of SCS on CBF, 2-compare observations made by two different methods, and 3-evaluate a possible correlation between the stimulated spinal segmental level and the modification of CBF. The results of our study confirm that SCS interacts with the mechanisms of regulation of CBF. The stimulation of different spinal cord levels in the same patient can produce different effects and such effects are reproducible. An increase of CBF is more likely to occur with the stimulation of the cervical spinal cord. In patients studied by both methods the sign of CBF changes induced by SCS was the same. Finally, in two patients the effect of SCS on CO2 autoregulation was studied with TCD. The results of such a study, although preliminary, suggest that CO2 and SCS have a competitive effect upon the mechanisms of regulation of CBF.

Regional Cerebral Blood Flow during Spreading Cortical Depression in Conscious Rats

Spreading cortical depression (SCD) of EEG activity was induced in one cerebral hemisphere of conscious restrained rats by direct current stimulation of the lateral frontal cortex. Regional CBF was measured using [14C]iodoantipyrine and brain dissection. An early phase of increased CBF was not measured in conscious rats, but an early relative hyperperfusion was measured if the resting CBF was first reduced by treatment with pentobarbital or indomethacin. A long-lasting reduction in CBF was measured in conscious rats following the passage of SCD. This flow reduction resolved after 3 h. In conscious rats, CBF decreased in the striatum and thalamus ipsilateral to the SCD, paralleling the CBF changes occurring in the cortex. The CBF change in these deep structures was abolished by pentobarbital. An early transient increase in regional CBF was measured in the cerebral cortex contralateral to the hemisphere involved with SCD in conscious rats. This early contralateral hyperperfusion was also abolished by pentobarbital or indomethacin but not by atropine or propranolol. The vascular response to SCD in conscious rats differs from that which occurs in anesthetized rats.

Microvascular Changes during the Early Phase of Experimental Bacterial Meningitis

We investigated the temporal profile of the changes in regional CBF (rCBF) and intracranial pressure (ICP) during the early phase of pneumococcal meningitis in the rat. rCBF, as measured by laser-Doppler flowmetry, and ICP were continuously monitored during 6 h post infection (p.i.). Brain edema formation was assessed by brain water content determinations. Meningitis was induced by intracisternal injection of 75 microliters of 10(7) colony-forming units/ml pneumococci (n = 7). In control animals (n = 6), saline was injected. There was no change in the rCBF or ICP of controls throughout the experiment. However, there was a dramatic increase in rCBF and ICP associated with brain edema formation in untreated meningitis animals. rCBF increased to 135.3 +/- 33.8% (mean +/- SD) in the untreated animals at 1 h p.i. and reached 211.1 +/- 40.5% at 6 h p.i. (p less than 0.05 compared with controls). ICP increased from 2.9 +/- 1.4 to 10.4 +/- 4.7 mm Hg at 6 h p.i. (p less than 0.05 compared with controls). Brain water content was significantly elevated (79.69 +/- 0.24 compared with 78.94 +/- 0.16% in the control group, p less than 0.05). We investigated the effect of dexamethasone (3 mg/kg i.p.), which was given prior to the induction of meningitis (n = 3) or at 2 h after pneumococcal injection (n = 5), indomethacin (10 mg/kg i.v., n = 5), and superoxide dismutase (SOD; 132,000 U/kg i.v. per 6 h, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous Monitoring of Cerebrocortical Blood Flow during Stimulation of the Cerebellar Fastigial Nucleus: A Study by Laser-Doppler Flowmetry

Laser-Doppler flowmetry was used to continuously monitor cortical CBF during electrical stimulation of the fastigial nucleus (FN). Rats were anesthetized with isoflurane (0.75-5%), paralyzed, and artificially ventilated. The LDF probe was placed over a target region of the parietal cortex through a burr hole. The hypertension associated with FN stimulation was prevented by spinal cord transection at C1 with arterial pressure maintained by i.v. infusion of phenylephrine. After cord transection, CBF changed linearly with changes in arterial pco2 (r = 0.93; n = 23). FN stimulation (50-100 microA, 50 Hz, 1 s on/1 s off) produced sustained increases in CBF that developed slowly, reaching 50% of maximum within 24 +/- 1 s of stimulation (n = 17). After stimulation, CBF returned to baseline gradually within a time period (84-540 s) proportional to the duration of the stimulation (r = 0.93; n = 15). The CBF response was stimulus frequency and intensity dependent, was elicited only from restricted sites in FN, and was abolished by atropine (1 mg/kg, i.v.) or pentobarbital (30 mg/kg, i.v.). The slow temporal profile of the cerebrovasodilation is compatible with the hypothesis that in cerebral cortex local neurons mediate the vasodilation by interstitial release of vasoactive agents rather than by a direct action of neural processes on blood vessels. LDF is an effective technique for monitoring phasic change in CBF and may be useful in studies of the intrinsic neurogenic control of the cerebral circulation.

The Effect of Fosinopril Sodium on Cerebral Blood Flow in Moderate Essential Hypertension

The effect of the angiotensin converting enzyme (ACE) inhibitor fosinopril sodium on regional cerebral blood flow (rCBF) was investigated in 8 patients with moderate essential hypertension. A constant dose of chlorthalidone (25 mg/day) was given to stimulate the renin angiotensin system, and fosinopril sodium was given in incremental doses (10 to 40 mg/day) with the aim of obtaining a diastolic blood pressure at or below 90 mm Hg. Regional CBF was measured with xenon-133 inhalation tomography. Repetitive measurements were made at the start of treatment and again after 4 to 12 weeks treatment in the resting supine position, and during lower body negative pressure (LBNP) as a substitute for the upright position. Four hours after the first 10 mg dose of fosinopril the mean arterial pressure (MAP) had been reduced from 127 +/- 13 mm Hg to 105 +/- 9 mm Hg (P less than .01) without any significant change in mean CBF (55 +/- 9 mL/(100 g X min) at baseline versus 52 +/- 9 mL/(100 g X min) after fosinopril). After prolonged treatment with chlorthalidone and fosinopril, mean CBF was still unchanged from baseline levels, when measured 4 and 24 h after a single dose of fosinopril, despite a 10% reduction in MAP (P less than .01). LBNP did not lead to any significant change in rCBF. The regional distribution of CBF was normal in all patients throughout the study. We conclude that treatment with fosinopril sodium causes a moderate fall in blood pressure without any adverse effects on rCBF.