Cerebral Blood Flow Levels Research Articles

Effect of hypothermia on brain multi-parametric activities in normoxic and partially ischemic rats

Hypothermia, as well as anesthesia, are known to protect the brain against ischemia, hypoxia and other pathological damages. One of the mechanisms of this improvement could be by lowering brain function, and thereby lowering oxygen demand. We examined the effect of hypothermia on brain function and blood supply in awake and anesthetized rats and studied the interaction between partial ischemia and the responses to hypothermia. The brain function multiprobe (BFM) used enabled simultaneous measurements of cerebral blood flow (CBF), mitochondrial NADH redox state, extracellular K + concentration, DC potential and ECoG from the cerebral cortex in rats whose brain temperature was lowered by 5 °C. Hypothermia was induced in awake, anesthetized and brain ischemic–anesthetized rats. In anesthetized and ischemic–anesthetized rats, the time required for lowering the brain temperature by 5 °C was five times less than in the normal awake animals. No significant changes in CBF and NADH levels were found in response to hypothermia in the awake animals. In contrast, a significant decrease in extracellular K + concentration was recorded under hypothermia, probably due to the lower rate of depolarization. Hypothermia in anesthetized and in ischemic–anesthetized rats did not significantly affect the levels of mitochondrial NADH, CBF and extracellular K +. Hypothermia under ischemia was expected to be more effective.

Alterations in Cerebral Blood Flow and Glucose Utilization in Mice Overexpressing the Amyloid Precursor Protein

We have used quantitative autoradiographic techniques to study the relationship between cerebral blood flow (CBF) and glucose utilization (CGU) in two lines of transgenic mice overexpressing Swedish mutant amyloid precursor protein (APP) and APP-derived Aβ peptides. Mice were studied at an age when there are no amyloid plaques. In the 2123 line, CBF was reduced only in telencephalic regions with no corresponding decrease in CGU. In 2576 transgenics, a line with higher levels of Aβ peptide, both CBF and CGU were reduced throughout the brain. The data indicate that Aβ induces alterations in resting CBF that are either associated with or independent of alterations in CGU and that occur in the absence of amyloid deposition in neuropil of blood vessels. These observations support the hypothesis that cerebrovascular and metabolic abnormalities are early events in the pathogenesis of Alzheimer's disease.

The ABC of Alzheimer's disease: cognitive changes and their management in Alzheimer's disease and related dementias.

Cognitive decline, commonly first recognized as memory impairment, is a typical feature of Alzheimer's disease (AD). Neuropathological changes in the cerebral cortex and limbic system lead to deficits in learning, memory, language, and visuospatial skills. The precise nature of cognitive dysfunction reflects the distribution of pathological changes in AD. These will vary along the disease severity continuum and may also depend on where the disease sits in the spectrum of dementia. For example, AD-related disorders such as Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) also show symptoms of cognitive decline and share several pathological features, including degeneration of cortical cholinergic and striatal dopaminergic neurons. In vascular dementia (VaD), there is often an unequal distribution of cognitive deficit, with severe impairment in some functions and relative sparing of others. Cholinesterase (ChE) inhibitors, which help restore acetylcholine levels in the brain, are licensed for the symptomatic treatment of AD and have shown additional benefit in related dementias. Physiological correlates of cholinergic function/dysfunction in the brain include regional cerebral blood flow, glucose metabolism, and cerebrospinal fluid levels of ChE enzymes. These variables represent valuable markers of the clinical efficacy of ChE inhibitors. However, direct assessment of cognitive improvement, stabilization or decline is usually considered the key efficacy parameter in clinical studies of ChE inhibitors in AD and related dementias. Large-scale, placebo-controlled clinical studies of ChE inhibitors have demonstrated efficacy in treating the cognitive impairments associated with AD. Randomized comparative studies of ChE inhibitors are now under way to directly compare symptomatic efficacy and effects on disease progression. Clinical trial data of the cognitive effects of ChE inhibitors in AD, LBD, PDD, and VaD are discussed in detail in this article. The benefits of long-term treatment on symptomatic improvement in cognition and further potential disease-modifying effects are highlighted.

Correlation of Sensorimotor Activation with Functional Magnetic Resonance Imaging and Magnetoencephalography in Presurgical Functional Imaging: A Spatial Analysis

In this study we investigated the spatial heterotopy of MEG and fMRI localizations after sensory and motor stimulation tasks. Both methods are frequently used to study the topology of the primary and secondary motor cortex, as well as a tool for presurgical brain mapping. fMRI was performed with a 1.5T MR system, using echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI activation was determined with a cross-correlation analysis. MEG source localization was performed with a single equivalent current dipole model and a current density localization approach. Distances between MEG and fMRI activation sites were measured within the same anatomical 3-D–MR image set. The central region could be identified by MEG and fMRI in 33 of 34 cases. However, MEG and fMRI localization results showed significantly different activation sites for the motor and sensory task with a distance of 10 and 15 mm, respectively. This reflects the different neurophysiological mechanisms: direct neuronal current flow (MEG) and secondary changes in cerebral blood flow and oxygenation level of activated versus non activated brain structures (fMRI). The result of our study has clinical implications when MEG and fMRI localizations are used for pre- and intraoperative brain mapping. Although both modalities are useful for the estimation of the motor cortex, a single modality may err in the exact topographical labeling of the motor cortex. In some unclear cases a combination of both methods should be used in order to avoid neurological deficits.

Neuropsychological assessments in relation to CBF after severe head injuries.

To determine whether neuropsychological outcome is related to cerebral blood flow (CBF) early in the recovery phase. Twelve consecutive patients (mean age of 30 years, range 15-48 years) with severe traumatic brain injuries were subjected to a neuropsychological test battery at admission to the rehabilitation unit and after 3, 6 and 12 months. CBF measurements were performed at admission and 6 and 12 months later with a high-resolution, two-dimensional regional cerebral blood flow system with 254 stationary detectors after 1 min of (133)Xe inhalation (70-100 MBq/l). Mean CBF values were within normal range already in the early post-acute phase and remained virtually unchanged during the first year of rehabilitation. A correlation was found between the individual CBF level and neuropsychological outcome 1 year after injury, particularly with regard to verbal memory capacity, reasoning capacity, and information processing speed.

Recovery of brain function during induced cerebral hypoperfusion.

We used the setting of clinically indicated internal carotid artery balloon test occlusions in 44 patients with inoperable carotid cavernous aneurysms or head and neck tumours to examine real-time changes in higher cerebral function that correlate with specific levels of cerebral blood flow. By making detailed haemodynamic and neurobehavioural measurements during the 30 min the carotid artery was occluded, we were able to quantify higher cerebral function patterns in relation to absolute cerebral blood flow (CBF) levels. We found that once the carotid artery was occluded, patients whose CBF averaged 47 ml/100 g/min (no different from baseline) maintained consistent performance on a sustained attention task; those whose CBF dropped to an average 37 ml/100 g/min had a reversible deterioration of sustained attention, and those whose CBF fell to 27 ml/100 g/min had impaired sustained attention that persisted until the carotid occlusion was reversed. The relevance of these results to the pathological state of clinical stroke is discussed with respect to the haemodynamic and physiological mechanisms that may determine how brain function is lost and regained in the setting of acute cerebral hypoperfusion.

MK801 decreases glutamate release and oxidative metabolism during hypoglycemic coma in piglets

Hypoglycemic coma increases extracellular excitatory amino acids, which mediate hypoglycemic neuronal degeneration. Cerebral oxygen consumption increases during hypoglycemic coma in piglets. We tested the hypothesis that the NMDA-receptor antagonist dizocilpine (MK801) attenuates the increase in cerebral oxygen consumption during hypoglycemia. We measured EEG, cerebral blood flow (CBF), cerebral oxygen consumption (CMRO 2) and cortical microdialysate levels of glutamate, aspartate and glycine in pentobarbital-anesthetized piglets during 60 min of insulin-induced hypoglycemic coma. NMDA-receptor distribution was measured by autoradiography. MK801 (0.75 mg/kg i.v.) was given within 5 min after onset of isoelectric EEG. Saline- and MK801-treated normoglycemic control animals were also studied. Brain temperature was maintained at 38.5±0.5°C. MK801 prevented the 5–10-fold increase in glutamate and aspartate occurring in saline-treated hypoglycemic animals, and attenuated the increase in CMRO 2. Increases in CBF of 200–400% during hypoglycemic coma were not affected by MK801. MK801 did not alter CBF, CMRO 2 or microdialysate amino acid levels in normoglycemic control animals. Parietal cortex corresponding to microdialysis sites was highly enriched in NMDA receptors, and the density and distribution overall of NMDA receptor binding sites were comparable to that reported in other species. We conclude that NMDA receptor activation plays a central role in hypoglycemia-induced glutamate release, and contributes to increased cerebral oxygen consumption. Neuroprotective effects of MK801 during hypoglycemia in piglets may involve inhibitory effects on glutamate release and oxidative metabolism.

A Scanning Technique to Measure Regional Cerebral Blood Flow and Oxyhemoglobin Level

OBJECTIVE The application of a laser scanning technique to measure regional cerebral blood flow (CBF) and tissue hemoglobin oxygenation (HbO2) using the rat closed cranial window preparation is described. METHODS Twenty-nine male Wistar rats were used to consecutively measure local CBF by laser Doppler flowmetry and tissue HbO2 by a microspectrophotometric method at multiple corresponding cortical locations. The scanning technique used a computer-controlled micromanipulator. Data from three experimental models are presented: the whisker stimulation model, the ischemia-reperfusion model, and the sinus-vein thrombosis model. Sequential changes in local CBF and HbO2 data before, during, and after stimulation, ischemia, and sinus thrombosis were examined. Data from predefined locations within the same region were correlated with the topographical location and then arranged in a three-dimensional image. RESULTS In the whisker stimulation model, we found a disproportionate increase in CBF (32 ± 12%) as compared with that of HbO2 (9 ± 4%) during stimulation. In the ischemia-reperfusion model, the three-dimensional image showed heterogeneous low CBF (depending on the area) and homogeneous HbO2 at a reduced level during ischemia and postischemic hyperperfusion. However, the range of oxygenation was normal after reperfusion. In the sinus-vein thrombosis model, drainage of the unsaturated blood via the collateral pathways was noted. CONCLUSION The laser scanning technique is useful for visualizing sequential changes in hemodynamic-metabolic interactions of cortical brain tissue. This technique can reveal phenomena not detected by traditional monitoring procedures.

A scanning technique to measure regional cerebral blood flow and oxyhemoglobin level.

The application of a laser scanning technique to measure regional cerebral blood flow (CBF) and tissue hemoglobin oxygenation (HbO2) using the rat closed cranial window preparation is described. Twenty-nine male Wistar rats were used to consecutively measure local CBF by laser Doppler flowmetry and tissue HbO2 by a microspectrophotometric method at multiple corresponding cortical locations. The scanning technique used a computer-controlled micromanipulator. Data from three experimental models are presented: the whisker stimulation model, the ischemia-reperfusion model, and the sinus-vein thrombosis model. Sequential changes in local CBF and HbO2 data before, during, and after stimulation, ischemia, and sinus thrombosis were examined. Data from predefined locations within the same region were correlated with the topographical location and then arranged in a three-dimensional image. In the whisker stimulation model, we found a disproportionate increase in CBF (32 +/- 12%) as compared with that of HbO2 (9 +/- 4%) during stimulation. In the ischemia-reperfusion model, the three-dimensional image showed heterogeneous low CBF (depending on the area) and homogeneous HbO2 at a reduced level during ischemia and postischemic hyperperfusion. However, the range of oxygenation was normal after reperfusion. In the sinus-vein thrombosis model, drainage of the unsaturated blood via the collateral pathways was noted. The laser scanning technique is useful for visualizing sequential changes in hemodynamic-metabolic interactions of cortical brain tissue. This technique can reveal phenomena not detected by traditional monitoring procedures.

A Scanning Technique to Measure Regional Cerebral Blood Flow and Oxyhemoglobin Level

A Scanning Technique to Measure Regional Cerebral Blood Flow and Oxyhemoglobin Level

Effects of cilostazol on cerebral blood flow, P300, and serum lipid levels in the chronic stage of cerebral infarction

The effects of cilostazol (Pletaal, Otsuka Pharmaceutical Co., Tokyo, Japan) on cerebral blood flow, P300 event-related potentials, and serum lipid levels were examined in patients in the chronic stage of cerebral infarction. This study included 20 patients (13 men and 7 women, mean age 67 ± 11 years) with cerebral infarction who had taken ticlopidine (100 mg orally, twice a day). Quantitative cerebral blood flow measurements by Patlak plot analysis, ultrasound examinations of the common carotid arteries, and measurements of P300 event-related potentials and serum lipid levels were performed. Ticlopidine was then replaced with cilostazol (100 mg orally, twice a day) while other medications remained unchanged. The same examinations were performed again 3 months later. After replacement of ticlopidine with cilostazol, cerebral blood flow significantly increased in the frontal white matter, temporal cortex, and occipital cortex compared with cerebral blood flow before replacement with cilostazol. Ultrasonograms of the common carotid arteries showed no significant differences in intima-media thickness before and after replacement. However, peak systolic velocity, time-averaged peak velocity, and volume flow all significantly increased after replacement. Blood flow in the frontal white matter showed a significant negative correlation with P300 latency before and after replacement of ticlopidine with cilostazol. And P300 latency improved significantly after replacement with cilostazol. Regarding lipid levels, total cholesterol, triglycerides, and remnant-like particles-cholesterol all decreased significantly after replacement with cilostazol. Cilostazol, an inhibitor of platelet aggregation, was thus concluded to be effective in improving cerebral blood flow, cerebral function, and serum lipid levels in patients in the chronic stage of cerebral infarction. Copyright © 2001 by National Stroke Association

The effect of altered cerebral blood flow on the cerebral kinetics of thiopental and propofol in sheep.

Thiopental and propofol are highly lipid-soluble, and their entry into the brain often is assumed to be limited by cerebral blood flow rather than by a diffusion barrier. However, there is little direct experimental evidence for this assumption. The cerebral kinetics of thiopental and propofol were examined over a range of cerebral blood flows using five and six chronically instrumented sheep, respectively. Using anesthesia (2.0% halothane), three steady state levels of cerebral blood flow (low, medium, and high) were achieved in random order by altering arterial carbon dioxide tension. For each flow state, 250 mg thiopental or 100 mg propofol was infused intravenously over 2 min. To quantify cerebral kinetics, arterial and sagittal sinus blood was sampled rapidly for 20 min from the start of the infusion, and 1.5 h was allowed between consecutive infusions. Various models of cerebral kinetics were examined for their ability to account for the data. The mean baseline cerebral blood flows for the "high" flow state were over threefold greater than those for the low. For the high-flow state the normalized arteriovenous concentration difference across the brain was smaller than for the low-flow state, for both drugs. The data were better described by a model with partial membrane limitation than those with only flow limitation or dispersion. The cerebral kinetics of thiopental and propofol after bolus injection were dependent on cerebral blood flow, despite partial diffusion limitation. Higher flows produce higher peak cerebral concentrations.

Relative contributions from neuronal and endothelial nitric oxide synthases to regional cerebral blood flow changes during forebrain ischemia in rats

The principal aim of this study was to examine the relative contributions from the neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively) in their capacity to modulate intra-ischemic cerebral blood flow (CBF) changes, in the ischemically vulnerable hippocampus and striatum. CBF changes were monitored, using laser-Doppler flowmetry, in rats subjected to 30 min of forebrain ischemia (right common carotid occlusion+hemorrhagic hypotension). Rats were pretreated with a selective nNOS inhibitor (ARR 17477), a NOS inhibitor that blocks both eNOS and nNOS (N(G)-nitro-L-arginine; L-NNA), or saline (control). In initial experiments, where ischemic MABP was targeted to exactly 30 mmHg, NOS inhibition reduced intra-ischemic cortical CBF from the control level of approximately 20% of baseline to 3% (L-NNA) or 6% (ARR 17477) of baseline. The statistically similar effects of the two NOS inhibitors confirmed that nNOS is the predominant NO source supporting intra-ischemic vasodilation in the cortex. In subsequent experiments, CBF was measured in the right hippocampus, and striatum, as well as the cortex, and, to reduce data variability, blood withdrawal was adjusted to achieve an intra-ischemic cortical CBF of 20% (controls) or 5% (NOS inhibited rats) of baseline. In those groups, mean ischemic MABP levels ranged from 28 to 32 mmHg. In controls, intra-ischemic CBF fell to 20%, 45%, and 47% of baseline in the cortex, hippocampus, and striatum, respectively. With nNOS inhibition, intra-ischemic CBF was further reduced to 5%, 15%, and 18% of baseline, respectively. However, with combined eNOS/nNOS inhibition, the CBF values were 5%, 37%, and 21%, respectively. These results suggest that the nNOS contribution to intra-ischemic vasodilation in vulnerable regions is substantially greater than eNOS. The significantly higher intra-ischemic CBF level in the hippocampus in combined eNOS/nNOS vs nNOS-inhibited rats may relate, in contrast to other regions, to a low eNOS influence on vascular function in that structure and CBF redistribution to the hippocampus when eNOS activity is blocked globally.

Inhibition of N-glycan processing alters axonal transport of synaptic glycoproteins in vivo

The principal aim of this study was to examine the relative contributions from the neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively) in their capacity to modulate intra-ischemic cerebral blood flow (CBF) changes, in the ischemically vulnerable hippocampus and striatum. CBF changes were monitored, using laser-Doppler flowmetry, in rats subjected to 30 min of forebrain ischemia (right common carotid occlusion+hemorrhagic hypotension). Rats were pretreated with a selective nNOS inhibitor (ARR 17477), a NOS inhibitor that blocks both eNOS and nNOS (N(G)-nitro-L-arginine; L-NNA), or saline (control). In initial experiments, where ischemic MABP was targeted to exactly 30 mmHg, NOS inhibition reduced intra-ischemic cortical CBF from the control level of approximately 20% of baseline to 3% (L-NNA) or 6% (ARR 17477) of baseline. The statistically similar effects of the two NOS inhibitors confirmed that nNOS is the predominant NO source supporting intra-ischemic vasodilation in the cortex. In subsequent experiments, CBF was measured in the right hippocampus, and striatum, as well as the cortex, and, to reduce data variability, blood withdrawal was adjusted to achieve an intra-ischemic cortical CBF of 20% (controls) or 5% (NOS inhibited rats) of baseline. In those groups, mean ischemic MABP levels ranged from 28 to 32 mmHg. In controls, intra-ischemic CBF fell to 20%, 45%, and 47% of baseline in the cortex, hippocampus, and striatum, respectively. With nNOS inhibition, intra-ischemic CBF was further reduced to 5%, 15%, and 18% of baseline, respectively. However, with combined eNOS/nNOS inhibition, the CBF values were 5%, 37%, and 21%, respectively. These results suggest that the nNOS contribution to intra-ischemic vasodilation in vulnerable regions is substantially greater than eNOS. The significantly higher intra-ischemic CBF level in the hippocampus in combined eNOS/nNOS vs nNOS-inhibited rats may relate, in contrast to other regions, to a low eNOS influence on vascular function in that structure and CBF redistribution to the hippocampus when eNOS activity is blocked globally.

High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.

Chapter 14 Non-invasive in vivo imaging of transplant function

Publisher Summary Positron emission tomography (PET) allows regional changes in brain metabolism, blood flow, and receptor binding to be detected in vivo and quantitated in both Parkinson's (PD) and Huntington's (HD) disease. Single photon emission tomography (SPECT) can also provide useful estimates of blood flow and receptor binding, and is more widely available than PET. It has the advantage that its longer-lived 123I and 99mTc-based tracers do not need to be manufactured on site, but is less sensitive than PET and susceptible to scatter artefact. There are two basic ways to use functional imaging when measuring the changes in regional cerebral function associated with neurodegenerative disorders and transplantation. First, abnormalities in resting regional cerebral metabolism, blood flow, and neuroreceptor binding can be studied in both the implanted tissue and the host brain. Second, patients can be asked to perform tasks while levels of regional cerebral blood flow are measured. In this way, the effects of stereotactically implanted tissue on patterns of regional cerebral activation can be studied in transplanted movement disorder patients.

Impaired cerebral autoregulation 24 h after induction of transient unilateral focal ischaemia in the rat.

Cerebral blood flow (CBF) and cerebral autoregulation have been investigated 24 h after transient focal ischaemia in the rat. Cerebral blood flow was measured autoradiographically before and during a moderate hypotensive challenge, to test autoregulatory responses, using two CBF tracers, (99m)Tc-d,l-hexamethylproyleneamine oxide and 14C-iodoantipyrine. Prior to induced hypotension, CBF was significantly reduced within areas of infarction; cortex (28 +/- 20 compared with 109 +/- 23 mL/100 g/min contralateral to ischaemic focus, P = 0.001) and caudate (57 +/- 31 compared with 141 +/- 32 mL/100 g/min contralaterally, P = 0.005). The hypotensive challenge (mean arterial pressure reduced to 60 mmHg by increasing halothane concentration) did not compromise grey matter autoregulation in the contralateral hemisphere; CBF data were not significantly different at normotension and during hypotension. However, in the ipsilateral hemisphere, a significant volume of cortex adjacent to the infarct, which exhibited normal flow at normotension, became oligaemic during the hypotensive challenge (e.g. frontal parietal cortex 109 +/- 15% to 65 +/- 15% of cerebellar flow, P < 0.01). This resulted in a 2.5-fold increase in the volume of cortex which fell below 50% cerebellar flow (39 +/- 34 to 97 +/- 46 mm3, P = 0.003). Moderate hypotension induced a significant reduction in CBF in both ipsilateral and contralateral subcortical white matter (P < 0.01). In peri-infarct caudate tissue, CBF was not significantly affected by hypotension. In conclusion, a significant volume of histologically normal cortex within the middle cerebral artery territory was found to have essentially normal levels of CBF but impaired autoregulatory function at 24 h post-ischaemia.

A FAIR Study of Motor Cortex Activation under Normo- and Hypercapnia Induced by Breath Challenge

In this study an arterial spin-tagging technique based on flow-sensitive alternating inversion recovery (FAIR) with single-shot spiral data acquisition was used to study how the basal cerebral blood flow (CBF) elevated by breath holding affects the regional cerebral blood flow (rCBF) response to focal brain activation in the motor cortex. Six subjects were examined using three types of activation studies. These were (a) bilateral finger tapping paced at 4 Hz under normal breathing, (b) repeated expiration breath holding of 30 s, and (c) simultaneous breath holding and finger tapping. It was found that in five of six subjects the prevailing CBF level adjusted by breath challenge and the increase in rCBF in motor cortex associated with bilateral finger tapping were completely additive. This finding from FAIR-based functional magnetic resonance imaging is in accordance with that reported from published positron emission tomography studies. The results indicate that in the majority of the subjects examined the regulatory mechanisms for vasodilatory reaction to CO2 and rCBF response to neural activation in motor cortex region are independent.

Activation-flow coupling with forepaw stimulation in female and male rats.

Activation-flow coupling (AFC), the coupling of changes in cerebral blood flow (CBF) with neuronal function, is the basis for many functional neuroimaging techniques. Prior studies have shown that females have higher cerebral blood flow levels than males and that estrogen may affect the mediators involved in AFC. No studies have compared AFC responses between males and females. We assessed the AFC responses to forepaw stimulation using signal-averaged laser Doppler (LD) measurements of CBF in alpha-chloralose anesthetized female and male rats. Results for various stimulus parameters were similar for both sexes except at 2 Hz where females had a higher blood flow response. These results suggest that the AFC responses in males and females are similar, but require further validation in humans.

Decreased Plasma Endothelin-1 Levels in Asymptomatic Type I Diabetic Patients with Regional Cerebral Hypoperfusion Assessed by Spect

The prevalence of stroke is increased in diabetic patients. The vasoconstrictor peptide endothelin-1 (ET-1) has been implicated in the development of cerebral vasospasm after stroke but its role in the physiological regulation of cerebral blood flow (CBF) is not well known. Our aim was to assess the relationship between CBF and plasma ET-1 levels in type I diabetic patients. Regional CBF was assessed semi-quantitatively by 99Tc m-hexamethylpropylene-amine-oxime ( 99Tc m-HMPAO) single photon emission computed tomography (SPECT) in 50 cerebral “regions of interest” (ROIs) of 19 type I diabetic patients without clinical evidence of cerebral disease, and 10 healthy control subjects. In both groups, plasma ET-1 levels were measured. Results showed that type I diabetic patients had significantly more hypoperfusion ROIs than control subjects. While up to 68.4% of the type I diabetic patients showed 3 or more hypoperfusion ROIs, only 10% of the control subjects did. Plasma ET-1 levels were lower in the type I diabetes subgroup with 3 or more hypoperfusion ROIs than in the type I diabetes subgroup with less than 3 hypoperfusion ROIs and in the control group. Moreover, an inverse correlation between the number of hypoperfusion ROIs and plasma ET-1 levels ( r = 0.47, p = 0.04) was found in the type I diabetes group. It is concluded that plasma ET-1 is decreased in type I diabetic patients with subclinical abnormalities of regional CBF assessed by cerebral SPECT. This fact may reflect a compensatory response to the reduction of the brain perfusion in order to prevent ischemic events in these patients.