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Background Dural arteriovenous fistulas (DAVFs) at the craniocervical junction are rare. Clinical manifestations range from acute or chronic myelopathy to subarachnoid hemorrhage to brainstem dysfunction. We encountered 4 cases of DAVFs at the craniocervical junction with progressive brainstem dysfunction and investigated the typical magnetic resonance imaging (MRI) features using T 2 -weighting imaging, susceptibility-weighted imaging, diffusion-weighted imaging, and contrast-enhanced imaging. Literature review revealed 10 case reports of DAVFs at the craniocervical junction manifesting with brainstem dysfunction. Case Description Four patients presented with DAVFs at the craniocervical junction with progressive brainstem dysfunction. Two patients underwent midline suboccipital craniotomy and C1 laminectomy, and 1 patient underwent transarterial endovascular embolization with Onyx 18 under general anesthesia. All neurologic deficits gradually improved after the operation. In the fourth case, the patient received conservative treatment and did not undergo any surgical procedure. MRI showed high signal intensity on T 2 -weighted imaging, magnetic resonance angiography, and magnetic resonance venography. Abnormal dilated vessels and flow-void signs around the lesions were detected on susceptibility-weighted imaging and contrast-enhanced images. Two cases revealed no abnormalities and had improved neurological deficits than those showed on diffusion-weighted imaging. Conclusions Susceptibility-weighted imaging, diffusion-weighted imaging, or contrast-enhanced scanning should be used during MRI examination of patients with progressive brainstem dysfunction to differentiate DAVFs at the craniocervical junction from other diseases, such as glioma or infection. Prompt diagnosis using MRI is of great significance in producing good functional outcomes of the patients. Highlights • SWI or contrast-enhanced imaging should be used to evaluate brainstem dysfunction. • Prompt diagnosis using DWI leads to good functional outcomes. [ABSTRACT FROM AUTHOR]

Transient bilateral common carotid artery occlusion (tBCCAO), followed by reperfusion, is a model of transient global hypoperfusion. In the present study we aimed to investigate the probable effects of Vanillic acid (VA) on some physiological parameters including cerebral hyperemia, blood-brain barrier (BBB) disruption, anxiety behaviors and neurological deficits induced by bilateral occlusion of the common carotid arteries and reperfusion (BCCAO/R) in rats. Rats were randomly divided into four groups; Sham, BCCAO/R, VA and VA+ BCCAO/R. Chronic cerebral hypoperfusion was induced after 2 weeks of pretreatment by VA. Subsequently, sensorimotor scores, elevated plus maze tests, cerebral hyperemia, and BBB disruption were evaluated 72 h after 30 min of BCCAO. Pretreatment of rats by VA improved sensory motor signs, anxiolytic behavior in BCCAO/R rats compared with untreated rats (p < 0.05). Further, VA attenuated reactive hyperemia and BBB disruption in BCCAO/R rats compared with untreated rats (p < 0.01). To our knowledge, this study is the first to reveal VA could attenuate reactive hyperemia and improve BBB disruption following BCCAO/R, and could improve neurological scores and anxiety like behaviors in this model of cerebral hypoperfusion. These results suggest that VA could be a promising pretreatment agent in cerebral hypoperfusion. [ABSTRACT FROM AUTHOR]

Purpose To investigate possible sources of quantification errors in global cerebral blood flow (CBF) measurements by comparing pseudo continuous arterial spin labeling (PCASL) and phase contrast (PC) MRI in anemic, hyperemic subjects. Methods All studies were performed on a Philips 3T Achieva MRI scanner. PC and PCASL CBF examinations were performed in 10 healthy, young adult subjects and 18 young adults with chronic anemia syndromes including sickle cell disease and thalassemia. CBF estimates from single and two compartment ASL kinetic models were compared. Numerical simulation and flow phantom experiments were used to explore the effects of blood velocity and B1 + on CBF quantification and labeling efficiency. Results PCASL CBF underestimated PC in both populations using a single compartment model (30.1 ± 9.2% control, 45.2 ± 17.2% anemia). Agreement substantially improved using a two-compartment model (− 8.0 ± 6.0% control, 11.7 ± 12.3% anemia). Four of the anemic subjects exhibited venous outflow of ASL signal, suggestive of cerebrovascular shunt, possibly confounding PC-PCASL comparisons. Additionally, sub-study experiments demonstrated that B1 + was diminished at the labeling plane (82.9 ± 5.1%), resulting in suboptimal labeling efficiency. Correcting labeling efficiency for diminished B1 + , PCASL slightly overestimated PC CBF in controls (− 15.4 ± 6.8%) and resulted in better matching of CBF estimates in anemic subjects (0.7 ± 10.0% without outflow, 10.5 ± 9.4% with outflow). Conclusions This work demonstrates that a two-compartment model is critical for PCASL quantification in hyperemic subjects. Venous outflow and B1 + under-excitation may also contribute to flow underestimation, but further study of these effects is required. [ABSTRACT FROM AUTHOR]

Background and Purpose: Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure.Methods: We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure.Results: There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P < .0001). This finding was consistent in sensitivity analysis that compared right and left hemispheric CPI from patients with both elevated and normal right atrial pressure.Conclusion: Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations. [ABSTRACT FROM AUTHOR]

Objective Oxygen transport to parenchymal cells occurs mainly at the microvascular level and depends on convective RBC flux, which is proportional in an individual capillary to the product of capillary hematocrit and RBC velocity. This study investigates the relative influence of these two factors on tissue PO2. Methods A simple analytical model is used to quantify the respective influences of hematocrit, RBC velocity, and RBC flow on tissue oxygenation around capillaries. Predicted tissue PO2 levels are compared with a detailed computational model. Results Hematocrit is shown to have a larger influence on tissue PO2 than RBC velocity. The effect of RBC velocity increases with distance from the arterioles. Good agreement between analytical and numerical results is obtained, and the discrepancies are explained. Significant dependence of MTCs on RBC velocity at low hematocrit is demonstrated. Conclusions For a given RBC flux in a capillary, the PO2 in the surrounding tissue increases with increasing hematocrit, as a consequence of decreasing IVR to diffusive oxygen transport from RBCs to tissue. These results contribute to understanding the effects of blood flow changes on oxygen transport, such as those that occur in functional hyperemia in the brain. [ABSTRACT FROM AUTHOR]

Purpose We examined how chewing rate and the extent of reactive hyperemia affect the blood flow in denture-supporting mucosa during chewing. Methods The left palatal mucosa was loaded under conditions of simulated chewing or simulated clenching for 30 s, and the blood flow during loading was recorded. We compared the relative blood flow during loading under conditions that recreated different chewing rates by combining duration of chewing cycle (DCC) and occlusal time (OT): fast chewing group, typical chewing group, slow chewing group and clenching group. The relationship between relative blood flow during simulated chewing and the extent of reactive hyperemia was also analyzed. Results When comparing the different chewing rate, the relative blood flow was highest in fast chewing rate, followed by typical chewing rate and slow chewing rate. Accordingly, we suggest that fast chewing increases the blood flow more than typical chewing or slow chewing. There was a significant correlation between the amount of blood flow during simulated chewing and the extent of reactive hyperemia. Conclusions Within the limitations of this study, we concluded that slow chewing induced less blood flow than typical or fast chewing in denture-supporting mucosa and that people with less reactive hyperemia had less blood flow in denture-supporting mucosa during chewing. [ABSTRACT FROM AUTHOR]

Summary Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O 2 ). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O 2 -consuming neuropil, we have here examined whether activity-dependent dips in O 2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O 2 tension elicit capillary hyperemia. Ex vivo experiments revealed that red blood cells (RBCs) themselves act as O 2 sensors that autonomously regulate their own deformability and thereby flow velocity through capillaries in response to physiological decreases in O 2 tension. This observation has broad implications for understanding how local changes in blood flow are coupled to synaptic transmission. [ABSTRACT FROM AUTHOR]

The brain possesses two intricate mechanisms that fulfill its continuous metabolic needs: cerebral autoregulation, which ensures constant cerebral blood flow over a wide range of arterial pressures and functional hyperemia, which ensures rapid delivery of oxygen and glucose to active neurons. Over the past decade, a number of important studies have identified astrocytes as key intermediaries in neurovascular coupling (NVC), the mechanism by which active neurons signal blood vessels to change their diameter. Activity-dependent increases in astrocytic Ca 2+ activity are thought to contribute to the release of vasoactive substances that facilitate arteriole vasodilation. A number of vasoactive signals have been identified and their role on vessel caliber assessed both in vitro and in vivo . In this review, we discuss mechanisms implicating astrocytes in NVC-mediated vascular responses, limitations encountered as a result of the challenges in maintaining all the constituents of the neurovascular unit intact and deliberate current controversial findings disputing a main role for astrocytes in NVC. Finally, we briefly discuss the potential role of pericytes and microglia in NVC-mediated processes. [ABSTRACT FROM AUTHOR]

Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. [ABSTRACT FROM AUTHOR]

Functional hyperemia is the regional increase in cerebral blood flow upon increases in neuronal activity which ensures that the metabolic demands of the neurons are met. Hypertension is known to impair the hyperemic response; however, the neurovascular coupling mechanisms by which this cerebrovascular dysfunction occurs have yet to be fully elucidated. To determine whether altered cortical parenchymal arteriole function or astrocyte signaling contribute to blunted neurovascular coupling in hypertension, we measured parenchymal arteriole reactivity and vascular smooth muscle cell Ca2+ dynamics in cortical brain slices from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We found that vasoconstriction in response to the thromboxane A2 receptor agonist U46619 and basal vascular smooth muscle cell Ca2+ oscillation frequency were significantly increased in parenchymal arterioles from SHR. In perfused and pressurized parenchymal arterioles, myogenic tone was significantly increased in SHR. Although K+-induced parenchymal arteriole dilations were similar in WKY and SHR, metabotropic glutamate receptor activation-induced parenchymal arteriole dilations were enhanced in SHR. Further, neuronal stimulation-evoked parenchymal arteriole dilations were similar in SHR and WKY. Our data indicate that neurovascular coupling is not impaired in SHR, at least at the level of the parenchymal arterioles. [ABSTRACT FROM AUTHOR]

Ischemia impairs blood supply to the brain, and reperfusion is important to restore cerebral blood flow (CBF) and rescue neurons from cell death. However, reperfusion can induce CBF values exceeding the basal values before ischemia. This hyperemic effect has been associated with a worse ischemic brain damage, albeit the mechanisms that contribute to infarct expansion are not clear. In this study, we investigated the influence of early postischemic hyperemia on brain damage and middle cerebral artery (MCA) properties and the effect of treatment with the endogenous antioxidant uric acid (UA). The MCA was occluded for 90 min followed by 24 h reperfusion in adult male Sprague-Dawley rats. Cortical CBF increases at reperfusion beyond 20% of basal values were taken as indicative of hyperemia. UA (16 mg/kg) or vehicle (Locke's buffer) was administered intravenously 135 min after MCA occlusion. Hyperemic compared with nonhyperemic rats showed MCA wall thickening (sham: 22.4 ± 0.8 µm; nonhyperemic: 23.1 ± 1.2 µm; hyperemic: 27.8 ± 0.9 at 60 mmHg; P < 0.001, hyperemic vs. sham) involving adventitial cell proliferation, increased oxidative stress, and interleukin-18, and more severe brain damage. Thus MCA remodeling after ischemia-reperfusion takes place under vascular oxidative and inflammatory stress conditions linked to hyperemia. UA administration attenuated MCA wall thickening, induced passive lumen expansion, and reduced brain damage in hyperemic rats, although it did not increase brain UA concentration. We conclude that hyperemia at reperfusion following brain ischemia induces vascular damage that can be attenuated by administration of the endogenous antioxidant UA. [ABSTRACT FROM AUTHOR]

Astrocytes are thought to play an important role in NVC, a process that allows the brain to locally control blood flow in response to changes in activity. However, there is an ongoing debate as to when, and under what conditions astrocyte activity is required. In the following review we set forth the hypotheses that astrocytes: (i) act to modulate but not initiate functional hyperemia and (ii) help set the basal tone state of the brain microvasculature by the tonic release of vaso-active messengers. Through these actions astrocytes could help match metabolic demand with supply over a spectrum of activity timescales. [ABSTRACT FROM AUTHOR]

Summary Based on previous fMRI and SPECT studies, it has been suggested seizures may be preceded by increased cerebral blood flow. Recently, we demonstrated transcutaneous regional cerebral oxygen saturation (rSO2) sensors are feasible for use in patients undergoing video EEG monitoring. We reanalyzed our data to determine if seizures were consistently marked by increased cerebral oxygenation. Patients with histories of generalized tonic clonic seizures (GTCS) were recruited into our study. All subjects were evaluated with continuous 30-channel scalp EEG and 2 rSO2 sensors placed on each side of the forehead. We calculated the mean rSO2 value for the 1 h epochs in the non-ictal (2 h prior to seizure onset) and pre-ictal (1 h prior to onset) periods. Seven primary/secondarily GTCS from 5 patients were captured. The mean rSO2 value in the non-ictal period was 75.6 ± 5.7%. This increased to 76.0 ± 6% in the pre-ictal period ( p = 0.032). Four of the 7 GTCS (57.1%) were marked by ≥3 sequential rSO2 values in the pre-ictal period that were ≥3 SDs greater than the mean non-ictal rSO2 value. Three GTCS (42.9%) were marked by sustained cerebral hyperemia for ≥15 consecutive readings. Our results suggest increased cerebral blood flow could be non-invasively used to predict seizure occurrence. [ABSTRACT FROM AUTHOR]

The Valsalva maneuver (VM) produces large and abrupt changes in mean arterial pressure (MAP) that challenge cerebral blood flow and oxygenation. We examined the effect of VM intensity on middle cerebral artery blood velocity (MCAv) and cortical oxygenation responses during (phases I-III) and following (phase IV) a VM. Healthy participants (n = 20 mean ± SD: 27 ± 7 years) completed 30 and 90% of their maximal VM mouth pressure for 10 s (order randomized) whilst standing. Beat-to-beat MCAv, cerebral oxygenation (NIRS) and MAP across the different phases of the VM are reported as the difference from standing baseline. There were significant interaction (phase * intensity) effects for MCAv, total oxygenation index (TOI) and MAP (all P < 0.01). MCAv decreased during phases II and III (P < 0.01), with the greatest decrease during phase III (-5 ± 8 and -19 ± 15 cm.s-1 for 30 and 90% VM, respectively). This pattern was also evident in TOI (phase III: -1 ± 1 and -5 ± 4%, both P 0 05). Phase IV increased MCAv (22 ± 15 and 34 ± 23cm.s-1), MAP (15 ± 14 and 24 ± 17mm Hg) and TOI (5 ± 6 and 7 ± 5%) relative to baseline (all P < 0.05). Cerebral autoregulation, indexed, as the %MCAv/%MAP ratio, showed a phase effect only (P < 0.001), with the least regulation during phase IV (2.4 ± 3.0 and 3.2 ± 2.9). These data illustrate that an intense VM profoundly affects cerebral hemodynamics, with a reactive hyperemia occurring during phase IV following modest ischemia during phases II and III. [ABSTRACT FROM AUTHOR]

Neurovascular coupling is understood to be the underlying mechanism of functional hyperemia, but the actions of the neurotransmitters involved are not well characterized. Here we investigate the local role of the neurotransmitter norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat by measuring O2, which is delivered during functional hyperemia. Extracellular changes in norepinephrine and O2 were simultaneously monitored using fast-scan cyclic voltammetry. Introduction of norepinephrine by electrical stimulation of the ventral noradrenergic bundle or by iontophoretic ejection induced an initial increase in O2 levels followed by a brief dip below baseline. Supporting the role of a hyperemic response, the O2 increases were absent in a brain slice containing the vBNST. Administration of selective pharmacological agents demonstrated that both phases of this response involve β-adrenoceptor activation, where the delayed decrease in O2 is sensitive to both α- and β-receptor subtypes. Selective lesioning of the locus coeruleus with the neurotoxin DSP-4 confirmed that these responses are caused by the noradrenergic cells originating in the nucleus of the solitary tract and A1 cell groups. Overall, these results support that non-coerulean norepinephrine release can mediate activity-induced O2 influx in a deep brain region. [ABSTRACT FROM AUTHOR]

In order to maintain normal brain function, it is critical that cerebral blood flow (CBF) is matched to neuronal metabolic needs. Accordingly, blood flow is increased to areas where neurons are more active (a response termed functional hyperemia). The tight relationships between neuronal activation, glial cell activity, cerebral energy metabolism, and the cerebral vasculature, known as neurometabolic and neurovascular coupling, underpin functional MRI (fMRI) signals but are incompletely understood. As functional imaging techniques, particularly BOLD fMRI, become more widely used, their utility hinges on our ability to accurately and reliably interpret the findings. A growing body of data demonstrates that astrocytes can serve as a "bridge," relaying information on the level of neural activity to blood vessels in order to coordinate oxygen and glucose delivery with the energy demands of the tissue. It is widely assumed that calcium-dependent release of vasoactive substances by astrocytes results in arteriole dilation and the increased blood flow which accompanies neuronal activity. However, the signaling molecules responsible for this communication between astrocytes and blood vessels are yet to be definitively confirmed. Indeed, there is controversy over whether activity-induced changes in astrocyte calcium are widespread and fast enough to elicit such functional hyperemia responses. In this review, I will summarize the evidence which has convincingly demonstrated that astrocytes are able to modify the diameter of cerebral arterioles. I will discuss the prevalence, presence, and timing of stimulus-induced astrocyte calcium transients and describe the evidence for and against the role of calcium-dependent formation and release of vasoactive substances by astrocytes. I will also review alternative mechanisms of astrocyte-evoked changes in arteriole diameter and consider the questions which remain to be answered in this exciting area of research. [ABSTRACT FROM AUTHOR]

The cerebral hyperaemia is one of the fundamental mechanisms for the central nervous system homeostasis. Due also to this mechanism, oxygen and nutrients are maintained in satisfactory levels, through vasodilation and vasoconstriction. The brain hyperaemia, or coupling, is accomplished by a group of cells, closely related to each other; called neurovascular unit ( NVU). The neurovascular unit is composed by neurones, astrocytes, endothelial cells of blood-brain barrier ( BBB), myocytes, pericytes and extracellular matrix components. These cells, through their intimate anatomical and chemical relationship, detect the needs of neuronal supply and trigger necessary responses (vasodilation or vasoconstriction) for such demands. Here, we review the concepts of NVU, the coupling mechanisms and research strategies. [ABSTRACT FROM AUTHOR]

Trendelenburg positioning in combination with pneumoperitoneum during robotic-assisted prostatic surgery possibly impairs cerebrovascular autoregulation. If cerebrovascular autoregulation is disturbed, arterial hypertension might induce cerebral hyperaemia and brain oedema, while low arterial blood pressure can induce cerebral ischaemia. The time course of cerebrovascular autoregulation was investigated during use of the Trendelenburg position and a pneumoperitoneum for robotic-assisted prostatic surgery using transcranial Doppler ultrasound. Cerebral blood flow velocity was correlated with arterial blood pressure and the autoregulation index (Mx) was calculated. In 23 male patients, Mx was assessed at baseline, after induction of general anaesthesia, during the Trendelenburg position (40-45°), and after repositioning. During the Trendelenburg position, Mx increased over time, indicating an impairment of cerebrovascular autoregulation. After repositioning, Mx recovered to baseline levels. It can be concluded that with longer durations of Trendelenburg position and pneumoperitoneum, cerebrovascular autoregulation deteriorates, and, therefore, blood pressure management should be adapted to avoid cerebral oedema and the duration of Trendelenburg position should be as short as possible. [ABSTRACT FROM AUTHOR]

Vascular reactivity is a surrogate marker for atherosclerosis and is predictive of cardiovascular outcome. Non-cardiovascular surgery is associated with perioperative cardiovascular complications in high-risk patients., To evaluate the impact of non-cardiovascular surgery on reactive hyperaemia and arterial endothelial function and to investigate the relationships between endothelial dysfunction and invasive (laparotomy) or minimally invasive (laparoscopic) surgery, we prospectively evaluated 106 patients undergoing abdominal surgery under general anaesthesia (71 laparotomy, 35 laparoscopy). Measurements of blood pressure, heart rate and pain (on a visual analogue scale ( VAS)) were undertaken. Brachial endothelium-dependent flow-mediated dilation ( FMD), endothelium-independent dilation, nitroglycerin ( NTG)-induced dilation and reactive hyperaemia were measured with high-resolution B-mode ultrasound on preoperative Day 1 (baseline), as well as 2 h and 1 and 7 days postoperatively., Blood pressure and heart rate were significantly higher 2 h postoperatively. Pain, as measured on the VAS, was higher ( P < 0.01) and reactive hyperaemia and FMD were significantly lower ( P < 0.001) at 2 h and 1 day postoperatively compared with values at baseline and on postoperative Day 7. By postoperative Day 7, FMD had recovered to baseline levels. Patients undergoing laparoscopic surgery had less FMD reduction on Days 1 and 7 (7.5 ± 1.5% and 7.9 ± 1.5%, respectively) compared with those undergoing laparotomy (6.4 ± 1.6% ( P = 0.001) and 7.0 ± 1.6% ( P = 0.006), respectively), consistent with potential cardiovascular benefit. Responses to NTG were stable throughout. Backward multivariate linear regression analysis indicated that FMD was independently related to age and VAS (model R = 0.486; F = 6.4; P < 0.001)., Reactive hyperaemia and arterial endothelial function are significantly reduced in the early postoperative period, particularly after laparotomy compared with laparoscopy, which may be related to postoperative cardiovascular events. [ABSTRACT FROM AUTHOR]

Context: The link between weight gain and cardiovascular risk characterized with circadian blood pressure variability [CBPV] and endothelial function [EF] is unexplored. Objective: To prospectively demonstrate weight gain in healthy adults, increases body fat [BF], enlarges waist circumference [WC], expands visceral adipose tissue [VAT], exacerbates systemic inflammation [sIF], worsens insulin resistance [IR] and enhances functional cardiovascular disease [CVD] risk. Design, setting and participants: Healthy men [n=11] and women [n=3] provided initial and eight-week postcaloric excess anthropometric and fasting laboratory measures. Functional CVD risk assessments: CBPV and resting EF were also obtained with 7-day automatic ambulatory BP monitoring and increased test finger peripheral arterial tone [PAT] relative to control [reported as relative hyperemia index (RHI)], respectively. Intervention: After determining individualized mean energy requirements for weight maintenance over 7-days, each participant received a personalized over feeding prescription (1.4 times; 41% carbohydrate, 44% fat, and 15% protein) for 8-weeks. Results: mean (SEM). Participants increased body weight [BW; +7.4(0.1) kg]*, body mass index [BMI; +2.5(0.2) kg/m2]*, BF [+2.0(0.01)%]*, WC [+8.2(1.0) cm]*, and VAT [+0.2(0.03) L]* and intrahepatic lipid [IHL + 0.0004(0.002) L] :*all p < 0.01. Increased subcutaneous adipose cell size [+0.3(0.01) ?L; p = 0.02] accompanied significant sIF [hs-CRP + 0.4(0.09) mg/dL; p = 0.04; leptin 6.63 ng/ml; p = 0.0008] and IR [fasting plasma glucose; [FPG] +7.0(0.6) mg/dL;p = 0.01, fasting insulin; [FI] +5.7(1.4) uIU/ml; p = 0.001, HOMA-IR +1.6(0.5); p = 0.02]. Abn CBPV {systolic [+5.4(0.8); p = 0.002, diastolic [+1.7(0.1); p = 0.07 and pulse pressure [PP] [+3.5(0.4); p = 0.003 mm Hg} or elevated heart rate [HR] [+4.9(0.5) bpm; p = 0.003] ensued. Resting RHI declined by 0.47(0.004) from initial 2.24(0.09) to 1.77(0.1); p = 0.001, indicating endothelial dysfunction [ED]. Conclusions: Controlled caloric excess in healthy human adults over only 8-weeks significantly increased BF, VAT, sIF [hs-CRP], IR [FPG, FI, HOMA-IR] and functional CVD risk [measured as abnormal circadian blood pressure variability and impaired resting endothelial function]. [ABSTRACT FROM AUTHOR]

Abstract: Variations in local neural activity are accompanied by rapid, focal changes in cerebral blood flow and volume. While a range of observations have shown that dilation occurs in cerebral arteries, there is conflicting evidence about the significance of volume changes in post-arteriole vessels. Here, we reconcile the competing observations using a new mathematical model of the hemodynamic response. First, we followed a ‘top down’ approach, without constraining the model, but using experimental observations at progressively more detailed scales to ensure physiological behaviour. Then, we blocked dilation of post-arteriole vessels, and predicted observations at progressively more aggregated scales (a ‘bottom up’ approach). Predictions of blood flow, volume, velocity, and vessel diameter changes were consistent with experimental observations. Interestingly, the model predicted small, slow increases in capillary and venous diameter in agreement with recent in vivo data. Blocking dilation in these vessels led to erroneous volume predictions. The results are further evidence that arteries make up the majority of blood volume increases during brief functional activation. However, dilation of capillaries and veins appears to be increasingly significant during extended stimulation. These are important considerations when interpreting results from different neurovascular imaging modalities. [Copyright &y& Elsevier]

Background: Management of severe traumatic brain injury (TBI) focuses on mitigating secondary insults. There are a number of biomarkers that are thought to play a part in secondary injury following severe TBI. Two of these, S100β and neuron-specific enolase (NSE), have been extensively studied in the setting of neurological injury. This pilot study was undertaken to investigate the relationship of S100β and NSE to clinical markers of severity and poor outcome: intracranial hypertension (ICH), and cerebral hypoperfusion (CH). Methods: Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled over an 18-month period. Inclusion criteria were: age > 18, admission within the first 6 h after injury, Glasgow Coma Scale (GCS) < 9 on admission, isolated TBI, and placement of an intraventricular catheter (IVC). Patients were managed according to an institutional protocol based on the Brain Trauma Foundation Guidelines. CSF was collected from the IVC on admission and twice daily for 7 days. S100β and NSE levels were analyzed by ELISA. CSF levels drawn before (PRE) and after (POST) 12-h time periods were compared to percentage time intracranial pressure (ICP) > 20 mmHg (% ICP) and cerebral perfusion pressure (CPP) < 60 mmHg (% CPP), and cumulative 'Pressure times Time Dose' (PTD) for episodes of ICP > 20 mmHg (PTD ICP) and CPP < 60 mmHg (PTD CPP). Statistical analysis was performed using the Student's t test to compare means and non-parametric Wilcoxon statistic to compare ranked data. Linear regression methods were applied to compare levels of S100β and NSE with ICP and CPP Results: Twenty-three patients were enrolled. The cohort of patients was severely injured and neurologically compromised on admission (admission GCS = 5.6 ± 3.1, Injury Severity Score (ISS) = 31.9 ± 10.6, head Abbreviated Injury Scale (AIS) = 4.4 ± 0.7, Marshall score = 2.6 ± 0.9). Elevated levels of S100β and NSE were found in all 223 CSF samples analyzed. ICH was found to be associated with PRE and POST S100β levels when measured as % ICP (r = 0.20 and r = 0.23, P < 0.01) and PTD ICP (r = 0.35 and r = 0.26, P < 0.001). POST increasing NSE levels were weakly correlated with increasing PTD ICP (r = 0.17, P = 0.01). PRE S100β levels were associated with episodes of CH as measured by % CPP (r = 0.20, P = 0.002) and both PRE and POST S100β levels were associated with PTD CPP (r = 0.24 and r = 0.23, P < 0.001). PRE and POST NSE levels were also associated with episodes of CH as measured by % CPP (r = 0.22 and r = 0.18, P < 0.01) and PTD CPP (r = 0.20 and r = 0.21, P < 0.01). Conclusions: In this preliminary analysis, S100β levels were associated with ICH and CH over a full week of ICP monitoring. We also found associations between CH and NSE levels in CSF of patients with severe TBI. Our results suggest that there is an association between levels of ICH and CH and these biomarkers when measured before episodes of clinically significant secondary insults. These markers of neuronal cell death demonstrate promise as both indicators of impending clinical deterioration and targets of future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Cutaneous blood flow (CBF) can be assessed non-invasively with lasers. Unfortunately, movement artefacts in the laser skin signal (LSsk) might sometimes compromise the interpretation of the data. To date, no method is available to remove movement artefacts point-by-point. Using a laser speckle contrast imager, we simultaneously recorded LSsk and the signal backscattered from an adjacent opaque surface (LSos). The completion of a first protocol allowed a definition of a simple equation to calculate the CBF from movement artefact-affected traces of LSsk and LSos. We then recorded LSsk and LSos before, during and for 5min after the tourniquet ischemia, both when subjects (n=8) were immobile or submitted to external passive movements of random intensity throughout the test. The typical post-occlusive reactive hyperemia trace was not identifiable within the LSsk recordings, with LSsk being 2 to 3 times higher during movements than in the immobile situation. After the calculation of CBF, traces in the immobile versus movement conditions were comparable, with the “r” cross-correlation coefficient being 0.930+/−0.010. Our method might facilitate future investigations in microvascular physiology and pathophysiology, specifically in subjects who have frequent or continuous involuntary movements. [Copyright &y& Elsevier]

Hyperperfusion syndrome--a syndrome of brain hyperemia observed after improved blood inflow into the central nervous system, regardless of the use of a stent/operation as a treatment method, and is described as a complication observed in 0-5% of treated patients. The authors present this problem on the basis of their own experience of the Department of General and Vascular Surgery of the Medical University of Silesia, a problem which has not been reported in Polish literature up to this time. The material contains 1127 patients treated due to stenosis of the extracranial segments of carotid arteries from January 2005 to August 2010, including 523 patients who underwent surgery and 604 patients treated with a stent. The authors analyse this clinical material from the point of view of symptoms that can suggest the occurrence of brain hyperperfusion syndrome. The material has been analysed retrospectively on the basis of case histories and nursing reports. [ABSTRACT FROM AUTHOR]

In the brain, neuronal activation triggers a local increase in cerebral blood flow, a response named functional hyperemia. The extent to which functional hyperemia faithfully reports brain activation, spatially or temporally, remains a matter of debate. Here, we used the olfactory bulb glomerulus as a neurovascular model and two-photon microscopy imaging to investigate the correlation between calcium signals in glutamatergic terminals of olfactory sensory neurons and local vascular responses. We find that, depending on odor stimulation intensity, vascular responses are differently coupled to calcium signals. Upon moderate odor stimulation, glomerular vascular responses increase accordingly with calcium signals. In contrast, in silent glomeruli neighboring strongly activated ones and in glomeruli adapting upon high odor stimulation, vascular responses are independent of or negatively coupled to presynaptic calcium signals, respectively. Hence, functional hyperemia, a key signal used in functional imaging, can be, at times, an unreliable marker of local brain activation. [ABSTRACT FROM AUTHOR]

Abstract: Cerebral ischemia causes blood flow derangements characterized by hyperemia (increased cerebral blood flow, CBF) and subsequent hypoperfusion (decreased CBF). We previously demonstrated that protein kinase C delta (δPKC) plays an important role in hippocampal neuronal death after ischemia. However, whether part of this protection is due to the role of δPKC on CBF following cerebral ischemia remains poorly understood. We hypothesized that δPKC exacerbates hyperemia and subsequent hypoperfusion resulting in CBF derangements following ischemia. Sprague–Dawley (SD) rats pretreated with a δPKC specific inhibitor (δV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after 2-vessel occlusion plus hypotension measured by 2-photon microscopy. In an asphyxial cardiac arrest model (ACA), SD rats treated with δV1-1 (pre- and post-ischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 neuronal death 7 days after ACA. These results suggest possible therapeutic potential of δPKC in modulating CBF and neuronal damage after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Background: Severe traumatic brain injury (TBI) was to be one of the major health problems encountered in modern medicine and had an incalculable socioeconomic impact. The initial cerebral damage after acute brain injury is often exacerbated by postischemic hyperthermia and worsens the outcome. Hypothermia is one of the current therapies designed to combat this deleterious effect. The brain tissue oxygen (Pti o 2)-guided cerebral perfusion pressure (CPP) management was successfully reduced because of cerebral hypoxic episodes following TBI. Materials and Methods: Forty-five patients with severe TBI whose Glasgow Coma Scale (GCS) score ranged between 4 and 8 during September 2006 and August 2007 were enrolled in China Medical University Hospital, Taichung, Taiwan. One patient with a GCS score of 3 was excluded for poor outcome. These patients were randomized into three groups. Group A (16 patients) was intracranial pressure/cerebral perfusion pressure (ICP/CPP)–guided management only, Group B (15 patients) was ICP/CPP guided with mild hypothermia, and Group C (14 patients) was combined mild hypothermia and Pti o 2 guided with CPP management on patients with severe TBI. All patients were treated with ICP/CPP management (ICP <20 mm Hg, CPP >60 mm Hg). However, the group with Pti o 2 monitoring was required to raise the Pti o 2 above 20 mm Hg. Length of intensive care unit stay, ICP, Pti o 2, Glasgow Outcome Scale (GOS) score, mortality, and complications were analyzed. Results: The ICP values progressively increased in the first 3 days but showed smaller changes in hypothermia groups (Groups B and C) and were significantly lower than those of the normothermia group (Group A) at the same time point. We also found out that the averaged ICP were significantly related to days and the daily variations [measured as (daily observation − daily group mean)2] of ICP were shown to the significantly different among three treatment groups after the third posttraumatic day. The values of Pti o 2 in Group C tended to rise when the ICP decreased were also observed. A favorable outcome is divided by the result of GOS scores. The percentage of favorable neurologic outcome was 50% in the normothermia group, 60% in the hypothermia-only group, and 71.4% in the Pti o 2 group, with statistical significance. The percentage of mortality was 12.5% in the normothermia group, 6.7% in the hypothermia-only group, and 8.5% in the Pti o 2 group, without statistical significance in three groups. Complications included pulmonary infections, peptic ulcer, and leukocytopenia (43.8% in the normothermia group, 55.6% in the hypothermia-only group, and 50% in the Pti o 2 group). Conclusions: Therapeutic mild hypothermia combined with Pti o 2-guided CPP/ICP management allows reducing elevated ICP before 24 hours after injury, and daily variations of ICP were shown to be significantly different among the three treatment groups after the third posttraumatic day. It means that the hypothermia groups may reduce the ICP earlier and inhibit the elicitation of acute inflammation after cerebral contusion. Our data also provided evidence that early treatment that lowers Pti o 2 may improve the outcome and seems the best medical treatment method in these three groups. We concluded that therapeutic mild hypothermia combined with Pti o 2-guided CPP/ICP management provides beneficial effects when treating TBI, and a multicenter randomized trial needs to be undertaken. [Copyright &y& Elsevier]

Abstract: To date, the majority of neurovascular coupling studies focused on the thalamic afferents'' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague–Dawley rats divided into 6 groups depending on the maintaining anesthetic — alpha-chloralose, pentobarbital, ketamine–xylazine, fentanyl–droperidol, isoflurane, or propofol. The somatosensory evoked potentials (SEP) were decomposed into four components and the question of which best predicts the hemodynamic responses was investigated. Results of the linear regression analysis show that the hemodynamic response is best correlated with the secondary and late cortico-cortical transmissions and not with the initial thalamic input activity in layer IV. Baseline cerebral blood flow (CBF) interacts with neural activity and influences the evoked hemodynamic responses. Finally, neurovascular coupling appears to be the same across all anesthetics used. [Copyright &y& Elsevier]

This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K+ channels to coronary reactive hyperemia. Ca2+-activated (BKCa), voltage-activated (Kv), and ATP-dependent (KATP) K+ channels were investigated. Studies were conducted in anesthetized miniature Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. tschemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BKCa (penitrem A; 10 μg/kg iv), K+ (4-aminopyridine; 0.3 mg/kg iv) and KATP (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced -30% compared with lean swine. Inhibition of BKCa channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of K+ channels significantly reduced the repayment of flow debt (-25%) in both lean and metabolic syndrome swine. Additional blockade of KATP channels further diminished (-.45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K+ channels to reactive hyperemia. [ABSTRACT FROM AUTHOR]

The ratio of pulse wave amplitude (PWA) during reactive hyperemia compared to baseline as measured by peripheral arterial tonometry (PAT) is a non-invasive measure of microvascular endothelial function referred to as the pulse wave amplitude reactive hyperemia index (PWA-RHI). Whether upstream conduit vessel structure may affect downstream resistance vessel PWA has not been clearly examined. We tested the hypothesis that digital PWA is influenced by brachial artery diameter (BAD) and that this association would influence comparison of PWA-RHI between genders. Measures of vascular structure and microvascular function were carried out in 115 patients varying in cardiovascular risk profiles (average age 57 years, male n = 79, CAD n = 43). PWA was assessed using plethysmography at baseline and following 5 minutes of brachial artery occlusion. BAD was assessed using high-resolution ultrasonography. Results: There was a negative association between BAD and PWA-RHI (r = -0.34, p < 0.05). Women had greater PWA-RHI and smaller BAD compared with men (p < 0.05). When co-varying for BAD, there were no longer gender differences in PWA-RHI. Moreover, when a sub-group of men and women without CAD (n = 40), matched for BAD, were examined, there were no gender differences in PWA-RHI. In conclusion, PWA-RHI obtained from PAT is associated with BAD. Studies examining gender differences in microvascular endothelial function with PAT may need to correct for BAD as a potential confounder. [ABSTRACT FROM AUTHOR]

Inhibition of the initial events occurring immediately after ischemia-reperfusion seems to be beneficial for reducing the extent of subsequent chronic neuronal cell injury. We investigated the effects of moderate hypothermia (32°C) commencing 30 min before ischemia on reactive hyperemia by measuring cerebral blood flow (CBF) with a laser-Doppler flowmeter at the initial ischemia-reperfusion stage (60 min) following 10 min of global cerebral ischemia in rats. In normothermia, CBF was increased to approximately 240% and decreased thereafter, although it remained at approximately 150% after 60 min of ischemia-reperfusion. In contrast, hypothermia increased CBF to more than 270% after ischemiareperfusion, then recovered to the basal level within 30 min. The period of reactive hyperemia under normothermia tended to be shortened by preadministration of an NMDA antagonist, in a manner similar to hypothermia. Furthermore, hypothermia inhibited the presence of cells with caspase-3-like immunoreactivity in the hippocampal CA1 sector after 8 h of ischemia-reperfusion. Our findings indicate that hypothermia tends to shorten the period of reactive hyperemia during the initial ischemia-reperfusion stage. This phenomenon may be partly associated with activation of NMDA receptors and a beneficial effect of hypothermia in resisting progression of the neurotoxic cascade in the first 8 h after ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

Migraine with aura (MA) is associated with cerebral hyper- and hypoperfusion during and after the attacks. Several attempts to estimate individual perfusion changes and asymmetries in patients with MA using transcranial Doppler (TCD) have not been consistent. In 70 patients with MA and 40 controls with migraine without aura (MoA) or without any history of migraine, interictally recorded TCD sequences were prospectively analysed. Formal curve analysis of the visually evoked flow response (VEFR) was performed semiautomatically. As a main parameter for functional vasomotor reactivity (fVMR), the visually evoked flow rate (VEFR%) was calculated. The VEFR% showed a significantly higher mean difference of 14.7 ± 12% in MA patients vs. 5.8 ± 4.4% ( P < 0.001) in controls. The significant asymmetry of fVMR in MA patients is suggested to reflect interattack persisting vasomotor changes which are of pathophysiological interest and may be used as a monitoring tool under prophylactic medication. [ABSTRACT FROM AUTHOR]

We previously reported an attenuation of both exercise hyperemia and measures of aerobic capacity in hypercholesterolemic mice. In this study, we expanded upon the previous findings by examining the temporal and quantitative relationship of hypercholesterolemia to aerobic and anaerobic capacity and by exploring several potential mechanisms of dysfunction. Eight-week-old wild type (n = 123) and apoE knockout (n = 79) C57BL/6J mice were divided into groups with distinct cholesterol levels by feeding with regular or high-fat diets. At various ages, the mice underwent treadmill ergospirometry. To explore mechanisms, aortic ring vasodilator function and nitrate (NOx) activity, urinary excretion of NOx, running muscle microvascular density and citrate synthase activity, as well as myocardial mass and histologic evidence of ischemia were measured. At 8 weeks of age, all mice had similar measures of exercise capacity. All indices of aerobic exercise capacity progressively declined at 12 and 20 weeks of age in the hypercholesterolemic mice as cholesterol levels increased while indices of anaerobic capacity remained unaffected. Across the four cholesterol groups, the degree of aerobic dysfunction was related to serum cholesterol levels; a relationship that was maintained after correcting for confounding factors. Associated with the deterioration in exercise capacity was a decline in measures of nitric oxide-mediated vascular function while there was no evidence of aberrations in functional or oxidative capacities or in other components of transport capacity. In conclusion, aerobic exercise dysfunction is observed in murine models of genetic and diet-induced hypercholesterolemia and is associated with a reduction in vascular nitric oxide production. [ABSTRACT FROM AUTHOR]

Energetic basis of neural activity provides a solid foundation for noninvasive neuroimaging with calibrated functional magnetic resonance imaging (fMRI). Calculating dynamic changes in cerebral oxidative energy utilization (CMRO2) is limited by uncertainties about whether or not the conventional blood oxygenation level-dependent (BOLD) model can be applied transiently using multimodal measurements of blood flow (CBF) and volume (CBV) that affect the BOLD signal. A prerequisite for dynamic calibrated fMRI is testing the linearity of multimodal signals within a temporal regimen, as assessed by signal strength (i.e., both intensity and width). If each hyperemic component (BOLD, CBV, CBF) is demonstrated to be linear with neural activity under various experimental conditions, then the respective transfer functions generated by deconvolution with neural activity should be time invariant and thus could potentially be used for calculating CMRO2 transients. Hyperemic components were investigated at 11.7 T in α-chloralose-anesthetized rats and combined with electrophysiological recordings of local field potential (LFP) and multiunit activity (MUA) from the cortex during forepaw stimulation, in which stimulus number and frequency were varied. Although relationships between neural activity and stimulus features ranged from linear to nonlinear, associations between hyperemic components and neural activity were linear. Specific to each hyperemic component, a universal transfer function (with LFP or MUA) yielded predictions in agreement with experimental measurements. The results identified a component of the BOLD signal that can be attributed to significant changes in CMRO2, even for temporal events separated by <200 ms. [ABSTRACT FROM AUTHOR]

Rapid sampling microdialysis (rsMD) directed towards the cerebral cortex has allowed identification of a combined time-series signature for glucose and lactate that characterizes peri-infarct depolarization in experimental focal ischaemia, but no comparable data exist for ‘classical’ cortical spreading depression (CSD) associated with hyperaemia in the normally perfused brain. Here, we examined the rsMD responses of dialysate glucose and lactate to five hyperaemic spreading depressions induced with intracortical microinjections, typically of 1 mol/L KCl, in open-skull preparations in five cats under chloralose anaesthesia. Depolarization was verified with microelectrodes, and laser speckle flowmetry was used to examine propagation of the events and perfusion responses near the MD probe. Ten minutes after depolarization, dialysate glucose fell and lactate rose by 28% and 58% respectively. There was no recovery of dialysate glucose 30 mins after depolarization. Mean baseline indicative cerebral blood flow was 25.5±4.1 mL/100 g/min and mean maximum hyperaemic increase was by 29.6±6 mL/100 g/min; hyperaemia remained present 30 mins after CSD. As CSD events are repetitive, frequent, and often clustered temporally in human acute brain injury, these results indicate a high risk of depletion of extracellular glucose in association with depolarization events of a pattern previously thought to be largely benign.Journal of Cerebral Blood Flow & Metabolism (2009) 29, 166–175; doi:10.1038/jcbfm.2008.108; published online 24 September 2008 [ABSTRACT FROM AUTHOR]

We evaluated cerebral blood flow by laser Doppler during 30 secs of hypoxia (0.10 FiO2) in anesthetized, ventilated adenosine 2a receptor knockout (A2aR KO) and wild-type (WT) mice to test the hypothesis that cerebral hypoxic hyperemia in KO mice would be attenuated. We also studied the effects of selective and nonselective A2aR antagonists. During 30 secs of hypoxia, PaO2 decreased significantly (P<0.05) and to a similar degree in both types of mice, whereas PaCO2 remained relatively stable. However, mean arterial blood pressure (MABP) decreased to a greater extent (P<0.05) during hypoxia in KO mice (58.6±1.5 mm Hg) than in WT animals (76.1±3.2 mm Hg). Consequently, in a separate group of mice, we stabilized and matched MABP during hypoxia. Hypoxic hyperemia was attenuated by 38% (P<0.05) in KO animals whose MABP was uncontrolled, and by 81% (P<0.05) in KO animals whose MABP changes were matched to the MABP in the hypoxic WT mice. In animals treated with adenosine antagonists, hypoxic hyperemia was decreased by 44% to 48% (P<0.05) in WT mice, but was without effect in KO mice. We conclude that adenosine via A2aR is responsible for a significant proportion of the hyperemia during hypoxia.Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1656–1664; doi:10.1038/jcbfm.2008.57; published online 11 June 2008 [ABSTRACT FROM AUTHOR]

Background. Severe malaria is characterized by microvascular obstruction, endothelial dysfunction, and reduced levels of ʟ-arginine and nitric oxide (NO). ʟ-Arginine infusion improves endothelial function in moderately severe malaria. Neither the longitudinal course of endothelial dysfunction nor factors associated with recovery have been characterized in severe malaria. Methods. Endothelial function was measured longitudinally in adults with severe malaria (n = 49) or moderately severe malaria (n = 48) in Indonesia, using reactive hyperemia peripheral arterial tonometry (RH-PAT). In a mixed-effects model, changes in RH-PAT index values in patients with severe malaria were related to changes in parasitemia, lactate, acidosis, and plasma ʟ-arginine concentrations. Results. Among patients with severe malaria, the proportion with endothelial dysfunction fell from 94% (46/49 patients) to 14% (6/42 patients) before discharge or death (P < .001). In severe malaria, the median time to normal endothelial function was 49 h (interquartile range, 20-70 h) after the start of antimalarial therapy. The mean increase in ʟ-arginine concentrations in patients with severe malaria was 11 μmol/L/24 h (95% confidence interval [CI], 9-13 μmol/L/24 h), from a baseline of 49 μmol/L (95% CI, 37-45 μmol/L). Improvement of endothelial function in patients with severe malaria correlated with increasing levels of ʟ-arginine (r = 0.56; P = .008) and decreasing levels of lactate (r = -0.44; P = .001). Conclusions. Recovery of endothelial function in severe malaria is associated with recovery from hypoargininemia and lactic acidosis. Agents that can improve endothelial NO production and endothelial function, such as ʟ-arginine, may have potential as adjunctive therapy early during the course of severe malaria. [ABSTRACT FROM AUTHOR]

Summary: Objective: To investigate pathophysiological factors underlying the presence of interictal hyperperfusion within the limits of the polymicrogyric (PMG) cortex in epileptic patients. Methods: Retrospective observational study on interictal perfusion by Single Photon Emission Computed Tomography (SPECT) in 16 patients with PMG and its correlations with a number of clinical and neurophysiological variables. Patients underwent video-EEG monitoring, neurological and psychiatric assessments, invasive EEG, and the interictal SPECT coregistered to Magnetic Resonance Imaging (MRI). Results: Patients with interictal hyperperfusion within the PMG cortex had a significantly higher spike rate on interictal EEG than patients with normal perfusion. Interictal hyperperfusion was not correlated to sex, age at epilepsy onset, age at evaluation, number of seizures per month, presence of initial precipitating insult (IPI), abnormal neurological examination, EEG findings, ictal semiology, and seizure outcome. The high interictal spike rate did not correlate to a high frequency of seizures per month. Conclusions: Our work provides further evidences for an intrinsic epileptogenesis of the PMG cortex during the interictal state, which accounts for the major role of PMG tissue in seizure generation. These results might help to increase our understanding about epileptogenesis related to the PMG cortex, providing new tools for more tailored epilepsy surgery in PMG patients. [Copyright &y& Elsevier]

Walter Moxon, MD, FRCP lived, practiced medicine, taught and wrote in the mid- to late- nineteenth-century Victorian England, mostly at Guy's Hospital, London. He was widely informed in the "Art of Physic," writing on a range of issues from cerebral lateralization of articulate speech to angina pectoris. The present paper will trace briefly his contributions to the newly discovered asymmetry of articulate speech in the left frontal lobe (1866) and will in more detail trace and analyze his 1881 Croonian Lectures at the Royal College of Physicians on a medical shibboleth referred to as "congestion of the brain." In a series of ingenious and rhetorically creative arguments with imaginative tropes, demonstrations, evolutionary accounts of cognition and blood metabolism for human/biped cognition, and cogent citations from the medical literature of the day, Moxon skillfully instructs his medical audience against the misleading notion of cerebral "congestion" as an underlying pathology for cognitive, motor, and sensory deficits seen in the clinic. In so doing, he provides the medical community with an in-depth glimpse at the circulatory system, its flow dynamics, and how they serve to meet the cognitive, motor, and sensory demands of upright bipedal man. [ABSTRACT FROM AUTHOR]

Cerebral hyperperfusion after carotid endarterectomy (CEA) results in cerebral hyperperfusion syndrome and cognitive impairment. The goal of the present study was to clarify the clinical significance of postoperative crossed cerebellar hypoperfusion (CCH) in patients with cerebral hyperperfusion after CEA by assessing brain perfusion with single-photon emission computed tomography (SPECT). Brain perfusion was quantitatively measured using SPECT and the [123I]N-isopropyl-p-iodoamphetamine-autoradiography method before and immediately after CEA and on the third postoperative day in 80 patients with ipsilateral internal carotid artery stenosis (≥70%). Postoperative CCH was determined by differences between asymmetry of perfusion in bilateral cerebellar hemispheres before and after CEA. Neuropsychological testing was also performed preoperatively and at the first postoperative month. Eleven patients developed cerebral hyperperfusion (cerebral blood flow increase of ≥100% compared with preoperative values) on SPECT imaging performed immediately after CEA. In seven of these patients, CCH was observed on the third postoperative day. All three patients with hyperperfusion syndrome exhibited cerebral hyperperfusion and CCH on the third postoperative day and developed postoperative cognitive impairment. Of the eight patients with asymptomatic hyperperfusion, four exhibited CCH despite resolution of cerebral hyperperfusion on the third postoperative day, and three of these patients experienced postoperative cognitive impairment. In contrast, four patients without postoperative CCH did not experience postoperative cognitive impairment. The presence of postoperative CCH with concomitant cerebral hyperperfusion reflects the development of hyperperfusion syndrome. Further, the presence of postoperative CCH in patients with cerebral hyperperfusion following CEA suggests development of postoperative cognitive impairment, even when asymptomatic. [ABSTRACT FROM AUTHOR]

Objective: High dietary salt intake decreases the arteriolar dilation associated with skeletal muscle contraction. Because hydrogen peroxide (H2O2) can be released from contracting muscle fibers, this study was designed to assess the possible contribution of H2O2 to skeletal muscle functional hyperemia and its sensitivity to dietary salt. Methods: The authors investigated the effect of catalase treatment on arteriolar dilation and hyperemia in contracting spinotrapezius muscle of rats fed a normal salt (0.45%, NS) or high salt (4%, HS) diet for 4 weeks. Catalase-sensitive 2',7'-dichlorofluorescein (DCF) fluorescence was measured as an index of H2O2 formation, and the mechanism of arteriolar dilation to H2O2 was probed in each group using pharmacological inhibitors. Results: DCF fluorescence increased with muscle contraction, but not if catalase was present. Catalase also reduced arteriolar dilation and hyperemia during contraction in both dietary groups. Exogenous H2O2 dilated arterioles in both groups, with greater responses in HS rats. Guanylate cyclase inhibition did not affect arteriolar responses to H2O2 in either group, but KCa or KATP channel inhibition equally reduced these responses, and KATP channel inhibition equally reduced functional hyperemia in both groups. Conclusions: These results indicate that locally produced H2O2 contributes to arteriolar dilation and hyperemia in contracting skeletal muscle, and that the effect of H2O2 on arteriolar tone in this vascular bed is mediated largely through K+ channel activation. High dietary salt intake does not reduce the contribution of H2O2 to active hyperemia, or alter the mechanism through which H2O2 relaxes arteriolar smooth muscle. [ABSTRACT FROM AUTHOR]

Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci – in particular, Streptococcus pneumoniae, the most frequent pathogen in bacterial meningitis – release hydrogen peroxide (H2O2) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H2O2 production on regional cerebral blood flow (rCBF) and intracranial pressure (ICP). Compared to wild-type D39 pneumococci, the increase of rCBF was diminished in meningitis induced by the H2O2 defective SpxB− mutant (maximum increase, 135%±17% versus 217%±23% of the individual baseline; P<0.01) or after treatment of D39-induced meningitis with H2O2-degrading catalase or with tetraethylammonium (TEA), a blocker of calcium-sensitive potassium channels, which mediate H2O2-induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB−, supporting the predominant role of bacterial H2O2. We conclude that in addition to host-sided mediators, bacterial-derived H2O2 acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis.Journal of Cerebral Blood Flow & Metabolism (2007) 27, 1792–1797; doi:10.1038/sj.jcbfm.9600474; published online 21 February 2007 [ABSTRACT FROM AUTHOR]

Abstract: After subarachnoid hemorrhage (SAH) cerebral metabolism is significantly impaired. Hyperglycolysis describes the reduction of oxidative metabolism followed by a relative increase of anaerobic glycolysis to maintain energy supply. This phenomenon is known in head injury but has not as yet been shown after SAH. This study was conducted to test the hypothesis that hyperglycolysis is present in SAH patients and is associated with vasospasm. A total of 105 measurements were conducted on 21 SAH patients (age 49±15 years, median World Federation of Neurosurgical Societies Grade 4) over the first 5 days following admission. Arteriovenous differences were calculated for oxygen (avDO2) and glucose (avDGlc). Relative hyperglycolysis was defined as metabolic ratio (MR=avDO2[mmol/L]/avDGlc[mmol/L])<3.44. Jugular-venous saturation for oxygen (SjvO2), mean arterial blood pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP) were monitored. Relative hyperglycolyis was recorded in 34% of studies after SAH. In hyperglycolytic studies both jugular-venous lactate and SjvO2 were significantly elevated (jugular-venous lactate 14.9±9.9 vs. 11.8±5.5 mg/dL, p =0.04; SjvO2: 70.0±18% vs. 81.7±9%, p =0.002). Relative hyperglycolysis is associated with outcome after SAH. In patients who died after SAH almost 50% of studies showed hyperglycolysis, whereas patients who survived without neurological deficit had no hyperglycolytic events. Relative hyperglycolysis is a common event after SAH. It may be associated with relative hyperemia but most importantly with outcome. [Copyright &y& Elsevier]

Abstract: Well-regulated blood flow within the brain is vital to normal function. The brain’s requirement for sufficient blood flow is ensured by a tight link between neural activity and blood flow. The link between regional synaptic activity and regional cerebral blood flow, termed functional hyperemia, is the basis for several modern imaging techniques that have revolutionized the study of human brain activity. Here, we review the mechanisms of functional hyperemia and their implications for interpreting the blood oxygen level-dependent (BOLD) contrast signal used in functional magnetic resonance imaging (fMRI). [Copyright &y& Elsevier]

Background: During sepsis progression microcirculatory dysfunction precedes macrocirculatory failure, partly explaining the occurrence of early organ dysfunction. The matter concerning microcirculatory dysfunction in the brain under septic conditions is less clear. We investigated the integrity of the activation flow coupling during sepsis progression in a rat model of septic shock. Methods: Chloralose-anesthetized rats (n = 30) were subjected to electric forepaw stimulation. Over the somatosensory cortex electrical activity and hemodynamic responses were recorded with surface electrodes and laser Doppler. After baseline recordings, vehicle, 1 or 5 mg/kg lipopolysaccharide (LPS) from Escherichia coli was given intravenously, and activation flow coupling, blood pressure and blood gases were investigated at regular time points up to 270 min. In the end lactate, glucose, neuron-specific enolase (NSE) and S-100B protein levels were measured. Results: Besides stable data from the control group, all LPS-treated rats developed signs of septic shock, which were more pronounced in the 5 mg/kg LPS group. Cerebral hyperemia occurred and was similar between the sepsis groups despite lower blood pressure levels in the 5 mg/kg LPS group. While the activation flow coupling remained intact in the 1 mg/kg LPS group, an uncoupling occurred in the 5 mg/kg group. First, the evoked flow velocity responses dropped 60 min after sepsis induction before the somatosensory amplitudes also decreased 120 min later. From similar NSE levels we suggest a functional rather than structural deficit explaining the difference in evoked potentials. Conclusions: For the first time we demonstrate microcirculatory dysfunction in the activation flow coupling of the brain. Inappropriate blood supply of neurons might explain the disturbance of neuronal function. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the C02-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal PCO2, CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO2 vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO2 inhalation. Measurements were repeated after sodium nitropnisside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 ± 75 vs. 297 ± 31%; P = 0.01, AUC ΔFBF: 173 ± 17 vs. 127 ± 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO2 vasoreactivity was impaired in patients compared with controls: 1.19 ± 0.1 vs. 1.54 ± 0.1 cm·s-1 ·mmHg-1; P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO2 vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in C02-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function. [ABSTRACT FROM AUTHOR]

Objective. To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc) and lactate (CMRLct). Methods. Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO2 from 36 ± 4 to 32 ± 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO2, CMRGlc and CMRLct. Results. Following hyperventilation, CBF was significantly reduced ( P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml·100 gr−1·min−1 were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO2, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Conclusions. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control. [ABSTRACT FROM AUTHOR]

The article presents a clinical review of spontaneous intracranial hypotension and spontaneous spinal cerebrospinal fluid (CSF) leaks. Intracranial hypotension causes orthostatic headaches and is commonly misdiagnosed. The article discusses cranial magnetic resonance imaging, myelography, treatments for intracranial hypotension including epidural blood patching, bed rest, and surgical CSF leak repair, and common magnetic resonance imaging findings, such as enhancement of the pachymeninges, subdural fluid collections, and pituitary hyperemia. INSETS: Connective Tissue Disorders Associated With Spontaneous Spinal...;Diagnostic Criteria for Headache Due to Spontaneous Spinal CSF....