Cerebral Vasoreactivity Research Articles

Reversible posterior leucoencephalopathy syndrome associated with anticancer drugs

Reversible posterior leucoencephalopathy syndrome (RPLS) is an underappreciated clinical-radiologic syndrome characterized by reversible cortical dysfunction preferentially involving the occipital lobes in conjunction with imaging findings of reversible subcortical oedema. As RPLS is being increasingly identified within the oncology population in association with cytotoxic chemotherapy and targeted agents, a review of the published work in English was carried out. A MEDLINE search of the published work in English was conducted to identify cases of RPLS in patients more than 16 years of age who were treated with anticancer drugs for documented malignancy. Only cases with adequate documentation regarding demographic and treatment data, cerebral magnetic resonance imaging and outcome were selected. We identified 24 patients with RPLS associated with a variety of anticancer drugs, most commonly complicating polychemotherapy and/or bevacizumab-containing regimens. There was a female predominance: 18 females and 6 males (P= 0.023). Women were of premenopausal age and were younger than males: 49.3 +/- 16.4 years versus 60.7 +/- 6.4 years (P= 0.09). Most patients presented with acute headache (67%), seizures (63%), confusion (54%) or cortical blindness (46%) with mean systolic and diastolic blood pressure of 168 +/- 15 and 98 +/- 15 mm Hg, respectively. Findings on magnetic resonance imaging showed hyperintense lesions on T(2)-weighted images in all patients, which involved the occipital lobes in 75% of patients; all patients experienced clinical and radiologic resolution within days to weeks. No deaths were directly attributed to RPLS. Combination and single-agent chemotherapy as well as novel anticancer drugs are associated with RPLS. We found RPLS to be overrepresented in premenopausal woman; the prevalence in this subgroup may be related to an anticancer drug-oestrogen interaction inducing altered cerebral vasoreactivity and endothelial dysfunction.

Cognitive and cerebral hemodynamic impairment in scleroderma patients

Neurological involvement in systemic sclerosis is unusual despite the possible cerebral localization of vascular lesions. The aim of this study was to evaluate cognitive performances and cerebral vasoreactivity in young scleroderma patients without any signs or symptoms of nervous system involvement. Sixteen scleroderma patients and 16 sex- and age-matched healthy subjects without vascular risk factors were included. A neuropsychological assessment for the evaluation of different areas of cognition was performed. For an assessment of cerebrovascular reactivity (CVR), each subject was submitted to hypercapnia with transcranial Doppler ultrasonography using the Breath-Holding Index (BHI). Patients had significantly lower adjusted mean levels of performance with respect to controls in the Modified Card Sorting Test (P < 0.001) and in the Trail Making Test Parts A and B (P < 0.001 and P < 0.05 respectively). Regarding CVR, BHI values were significantly lower in patients with respect to controls: 0.82 +/- 0.44 vs. 1.34 +/- 0.18, P < 0.0001. These findings show the presence of reduced performances of executive functions in scleroderma patients. The associated alteration of CVR in the absence of other apparent causes of cerebrovascular impairment suggests that cognitive problems may be related to an alteration in cerebral perfusion regulation specifically linked to the disease. Further studies are needed to evaluate whether cognitive changes may be positively influenced by treatments aimed to improve vessels functionality in scleroderma patients.

Carotid intima‐media thickness and cerebrovascular reactivity in long‐term type 1 diabetes mellitus

Diabetes mellitus (DM) is one of the leading risk factors for cerebrovascular diseases. Both macro- and microvascular damage may occur. The aim of the present work was to assess intima-media thickness as well as cerebral vasoreactivity in patients suffering from type 1 diabetes mellitus (IDDM). Intima-media thickness and resting middle cerebral artery blood flow velocity was measured in 33 IDDM patients and 31 healthy controls. After baseline investigations, 30 seconds of breath holding (BH) and 60 seconds of voluntary hyperventilation (HV) were performed by the subjects. Transcranial Doppler measurements were performed in each case after vasodilatory (BH) and vasoconstrictor (HV) stimuli. Cerebrovascular reactivity was expressed as the percentage of change of the middle cerebral mean blood flow velocity after BH or HV. IDDM patients showed a significantly larger intima-media thickness (0.1 +/- 0.02 mm) than healthy controls (0.06 +/- 0.006 mm, p < 0.001). Cerebrovascular reactivity after BH was less intensive in diabetic patients (19.3 +/- 16.1%) than that of the control subjects (38.7 +/- 22.8%, p < 0.01). Similarly, HV induced a less-pronounced decrease of cerebral blood flow velocity in diabetic subjects (-30.1 +/- 13.2%) than in nondiabetics (-37.6 +/- 17.0%, p < 0.05). Our results refer to early macro- and microangiopathic involvement of the cerebral vessels, which develop in parallel with angiopathies of the other organs, such as nephropathy and retinopathy. Further prospective studies are needed to clarify the role of these macro- and microangiopathic changes in the development of cerebrovascular complications in patients suffering from DM.

Statins and Gender-Related Difference in Endothelial Function in Cerebral Small Vessel Disease

To the Editor: We read with great interest the article by Dr Lavallee and colleagues1 dealing with the effect of the high dose of statin administration on cerebral vasoreactivity in patients with cerebral small vessel disease. The results of their study demonstrated that 3-month treatment with 80 mg atorvastatin per day did not significantly improve brachial and carotid artery endothelium-dependent vasodilatory responses in patients with recent lacunar stroke. The authors also indicated that the same dose of atorvastatin markedly reduced the low-density …

Cerebrovascular reactivity and dynamic autoregulation in ischaemic subcortical white matter disease

Background:It has been suggested that impaired cerebral autoregulation and vasodilatory capacity may play in role in the pathogenesis of the leukoaraiosis seen in small vessel disease. Adequate perfusion of the...

SU‐FF‐I‐126: Varied Vasomotor Responses Among Brain Territories in Unilateral ICA Stenosis Patients Studied Using Breath‐Hold BOLD MRI

Introduction: Patients with significant internal carotid artery (ICA) stenosis increase the incidence of ischemic stroke and benefit from carotid interventions, such as carotid angioplasty with stenting (CAS). Hyperperfusion syndrome usually causes disastrous outcome if occurred after carotid interventions. In recent studies, impaired cerebral vasoreactivity (CVR) is considered as one of the predictors for hyperperfusion syndrome. Hypercapnia stresses such as breath holding result in vasodilatation in human subjects. Thus combining breath holding and BOLD MRI may be a useful method to characterize the impaired CVR in patients prone to hyperperfusion after CAS. Most recently, Leoni et. al. found different hemodynamic response among different brain territories in normal subjects during breath holding. The aim of this study was to evaluate the varied hemodynamic responses among different brain territories in unilateral ICA stenosis patients using the same MRI method. Methods: Six patients with unilateral ICA stenosis participated in this study and were asked to hold their breath for 15 sec. Three cycles of the breath holding task were performed. A single‐shot T2* gradient‐echo EPI sequence was used for BOLD measurements at a 1.5T scanner. Twenty axial slices were acquired to cover the whole brain. Echo‐planar images were spatial normalized to the MNI template and averaged BOLD signal time curves were drawn from six regions of interest, i.e. ACA, MCA and PCA on both sides. To show the extent of voxels with significant BOLD signal changes, a correlation analysis (p&lt;0.05, corrected) was applied using the averaged signal time curve from the whole brain tissue. Results and Conclusion: In summary, our results showed the impaired CVR in patients with ICA stenosis was territory dependent (Fig. 2). Detailed analysis of the hemodynamic responses measured from breath‐holding BOLD MRI may help predict hyerperfusion syndrome after CAS.

Change in Cerebral Perfusion after Carotid Angioplasty with Stenting Is Related to Cerebral Vasoreactivity: A Study Using Dynamic Susceptibility-Weighted Contrast-Enhanced MR Imaging and Functional MR Imaging with a Breath-Holding Paradigm

Carotid angioplasty with stent placement (CAS) is an optional treatment for significant carotid stenosis. Cerebral vasoreactivity (CVR), representing the reserve capacity of cerebral perfusion, usually decreases in patients with severe carotid stenosis. This study aimed to investigate the relationship between the baseline CVR assessed by functional MR imaging (fMRI) and the changes in cerebral blood flow (CBF) after CAS. Fourteen patients with at least 70% unilateral carotid stenosis underwent CAS. Baseline CVR was evaluated by fMRI a under breath-holding paradigm. CBF was assessed by dynamic susceptibility-weighted contrast-enhanced MR imaging before and 3-5 days after CAS. The lateral index (LI) was defined as (n - L) / (n + L), where n and L represent the number of activated voxels in fMRI on the normal and lesion hemispheres, respectively. No subject had clinical evidence of hyperperfusion syndrome. The LI represented baseline CVR. Patients were divided into normal (LI < 0, n = 6) and impaired (LI > 0, n = 8) CVR groups. The CBF on the normal and lesion sides was calculated separately. CBF increment on the lesion side after CAS was significantly higher in the impaired CVR group than that in the normal CVR group (P = .035). There was a significantly positive correlation between CVR impairment and the CBF increment (P = .026). fMRI could be a reproducible tool in evaluating CVR. After CAS, early CBF changes on the lesion side are more prominent in patients with impaired CVR. Baseline CVR might predict early CBF increase after CAS.

Placebo-Controlled Trial of High-Dose Atorvastatin in Patients With Severe Cerebral Small Vessel Disease

Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease. Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations. At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5-14.7) and carotid (mean, -0.25%; 95% CI, -1.17-0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39-4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries. We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.

STAGED ANGIOPLASTY FOR CAROTID ARTERY STENOSIS TO PREVENT POSTOPERATIVE HYPERPERFUSION

Hyperperfusion (HP) is a rare but potentially devastating complication after carotid revascularization. This report describes the clinical efficacy of staged angioplasty (SAP) for carotid artery stenosis to prevent HP after carotid revascularization. Eighteen of 143 patients with high-grade internal carotid artery stenosis scheduled for angioplasty were considered at high risk of postprocedure HP based on their severely impaired cerebral blood flow (CBF) and cerebral vasoreactivity, which were determined using single-photon emission computed tomography with acetazolamide. Nine of the high-risk patients were treated with carotid artery stenting and the other 9 were treated with SAP, which consisted of balloon angioplasty with undersized balloon catheters (Stage 1) followed by carotid artery stenting 1 to 2 months later (Stage 2). In the regular carotid artery stenting group, 5 of 9 patients (56%) showed HP phenomenon on single-photon emission computed tomography just after stenting, and 1 patient (11%) developed status epilepticus owing to HP. In the SAP group, none of the 8 patients treated by SAP or the 1 patient who required stent placement during the first stage owing to a wall dissection developed postprocedure HP phenomenon or HP syndrome. SAP decreased the HP phenomenon on single-photon emission computed tomography after performing these procedures in selected patients. Although additional intervention is needed, SAP is considered a relatively simple and effective method to avoid HP in patients at high risk of HP after carotid revascularization.

Vasoreactivity and peri-infarct hyperintensities in stroke

It is unknown if impaired cerebral vasoreactivity recovers after ischemic stroke, and whether it compromises perfusion in regions surrounding infarct and other vascular territories. We investigated the regional differences in CO2 vasoreactivity (CO2 VR) and their relationships to peri-infarct T2 hyperintensities (PIHs), chronic infarct volumes, and clinical outcomes. We studied 39 subjects with chronic large middle cerebral artery territory infarcts and 48 matched controls. Anatomic and three-dimensional continuous arterial spin labeling imaging at 3-Tesla MRI were used to measure regional cerebral blood flow (CBF) and CO2 VR during normocapnia, hypercapnia, and hypocapnia in main arteries distributions. Stroke patients showed a significantly lower augmentation of blood flow at increased CO2 but greater reduction of blood flow with decreased CO2 than the control group. This altered vasoregulatory response was observed both ipsilateral and contralateral to the stroke. Lower CO2 VR on the stroke side was associated with PIHs, greater infarct volume, and worse outcomes. The cases with PIHs (n = 27) had lower CBF during all conditions bilaterally (p < 0.0001) compared to cases with infarct only. Perfusion augmentation is inadequate in multiple vascular territories in patients with large artery ischemic infarcts, but vasoconstriction is preserved. Peri-infarct T2 hyperintensities are associated with lower blood flow. Strategies aimed to preserve vasoreactivity after an ischemic stroke should be tested for their effect on long-term outcomes.

Cerebral vasoreactivity decreases overnight in severe obstructive sleep apnea syndrome: A study of cerebral hemodynamics

Background OSAS has been associated with surrogate markers of atherosclerosis and is a known risk factor for stroke. However, there is limited data on the effects of recurring apneas in severe OSAS on cerebral circulation and their consequences on cerebrovascular reactivity and compliance. Objective To evaluate cerebral blood flow velocity (CBFV) changes and vascular compliance in patients with severe obstructive sleep apnea syndrome (OSAS) using transcranial Doppler sonography (TCD) and cerebral pulse transit time (PTT). Methods Seven patients (1 woman, 6 men, mean age 57.4 years) with severe OSAS underwent polysomnography at the sleep laboratory of the Neurology Department of Innsbruck Medical University. TCD was performed continuously during the whole night using a pulsed wave probe and was co-registered with routine polysomnography. Cerebrovascular reactivity was assessed by calculation of apnea and hypopnea-related CBFV changes. Arterial compliance was characterized by PTT derived from phase difference analysis between ECG and TCD signals. Sleep time was dichotomized into periods with high density of consecutive respiratory events (CRE) vs. periods with low density of consecutive respiratory events (non-CRE). TCD measurements of CBFV showed a regular, undulating pattern with flow minima immediately before apneas or hypopneas and maxima closely after their termination, reciprocally to peripheral O 2 saturation. CBFV reactivity was significantly diminished in CRE compared to non-CRE periods. PTT phase differences were reduced in non-CRE, and even more so in CRE periods, compared to initial wake phases. Conclusion We found severe disturbances of cerebrovascular reactivity in OSAS patients. Our data demonstrate loss of vasoreactivity and increase of arterial stiffness, indicated by CBF hyporeactivity and PTT reduction, especially during CRE periods. These changes are likely to impair cerebral circulation and may be detrimental to the endothelium.

Does NO regulate the cerebral blood flow response in hypoxia?

To study whether nitric oxide (NO) affects the CBF response to hypoxic and carbon monoxide (CO) hypoxia. We incrementally reduced arterial oxygen content in rats, by decreasing the concentration of inspired oxygen (20 rats) or by repeated CO inhalation (20 rats), and measured local CBF using the hydrogen clearance method. Ten animals of each group received 80 mg/kg NO synthase (NOS) inhibitor N-monomethyl-L-arginine intravenously prior to hypoxia, while 10 rats served as controls. Inhibition of NOS decreased mean CBF by 30% and increased cerebrovascular resistance by 70%. Under hypoxic hypoxia, mean oxygen reactivity of CBF (relative change of CBF to a change of arterial oxygen content) was 7.8%/vol% in control animals and 3.3%/vol% after NOS inhibition (P < 0.02). Under CO hypoxia, mean oxygen reactivity was 7.3%/vol% in control animals and 5.1%/vol% after NOS inhibition (P < 0.05). Inhibition of NOS diminished significantly the cerebral vasodilatory response during hypoxic hypoxia (P < 0.05) but only to a lesser extent during CO hypoxia. These observations suggest that NO is involved in cerebral oxygen vasoreactivity, particularly in severe hypoxia.

Impaired Cerebral Vasomotor Activity in Spontaneous Intracerebral Hemorrhage

Impairment of cerebrovascular autoregulation may promote secondary brain injury in acute brain insults. Until now, only limited data are available on autoregulation in patients with spontaneous intracerebral hemorrhage. In the current study, we aimed to investigate cerebrovascular reactivity and its significance for outcome in spontaneous intracerebral hemorrhage. We continuously recorded mean arterial pressure, intracranial pressure, and cerebral perfusion pressure for mean 95 hours in 20 patients with spontaneous intracerebral hemorrhage. The moving correlation coefficient between mean arterial pressure and intracranial pressure (pressure reactivity index), an index of cerebral vasoreactivity, was calculated from the available artifact-free monitoring time (mean, 50.4 hours). In the univariate analysis pressure reactivity index (r=0.66; P=0.002), hemorrhage volume (r=0.62; P=0.007), cerebral perfusion pressure (r=-0.71; P=0.001), mean arterial pressure (r=-0.61; P=0.005), and hematoma growth (r=0.53; P=0.02) significantly correlated with National Institutes of Health Stroke Scale Score at discharge. In a multivariate stepwise linear regression model, pressure reactivity index remained the only independent predictor of outcome (beta=0.659; P=0.004). In the subgroup of patients with pressure reactivity index greater than a functional threshold of >0.2, the correlation between mean cerebral perfusion pressure and outcome remained significant (r=-0.73; P=0.0102), whereas National Institutes of Health Stroke Scale Score at discharge did not correlate with cerebral perfusion pressure in patients with pressure reactivity index <0.2 (r=-0.05; P=0.9078). We found evidence for impaired cerebral vasomotor activity as measured by pressure reactivity index in patients with spontaneous intracerebral hemorrhage. We suggest that impaired cerebrovascular reactivity contributes to poor outcome in intracerebral hemorrhage patients. This effect may be mediated by fluctuations in cerebral perfusion.

Improved Cerebral Vasoreactivity following Percutaneous Transluminal Angioplasty with Stenting of High-Grade Internal Carotid Artery Stenosis

Background: The aim of this study was to assess the effects of percutaneous transluminal angioplasty with stenting on cerebral vasoreactivity in carotid stenosis (CS). Methods: We studied the changes in the middle cerebral artery using transcranial Doppler and the breath-holding index (BHI) after hypercapnia in 33 patients with CS (15 symptomatic, 18 asymptomatic) before and 1 day and 1 month after stenting. Results: One day after stenting, the BHI significantly increased (p < 0.01) on the previously stenotic side in all patients. One month after stenting, the BHI was significantly higher on the contralateral side of asymptomatic (p < 0.05) and symptomatic patients (p < 0.01). Conclusion: Percutaneous transluminal angioplasty with stenting results in increasing improvement close to normalization of impaired cerebral vasoreactivity in patients with symptomatic and asymptomatic high-grade CS.

Patent foramen ovale detected by near-infrared spectroscopy in patients suffering from migraine with aura

There is an increased prevalence of patent foramen ovale (PFO) in women with migraine with aura (MwA) compared to controls, but the role of PFO in triggering aura is still debated. The aim of this study was to test a group of women suffering from MwA with near-infrared spectroscopy (NIRS), to assess the NIRS capability of discriminating between subjects with and without PFO. Eighty-eight MwA patients (mean age 37.4+/-10.7 years, range 16-62 years) underwent NIRS measurement of the cerebral variations of the oxygenated (O2Hb) and reduced haemoglobin (HHb) during breath-holding. The prevalence of O2Hb vs. HHb was used to assess the presence of PFO. As a gold standard, the presence of PFO was assessed by transcranial Doppler sonography (TCD). At the TCD analysis 48 patients (55%) showed PFOs, 32 of which were permanent. NIRS correctly detected 36 subjects out of 40 without PFO, and 38 subjects out of 48 having PFO: sensitivity was 79%; specificity was 90%. All the false negatives were permanent shunts. MwA patients with PFO showed a delayed increase in the O2Hb concentration and a reduced oxygenation with respect to subjects without PFO. NIRS is effective in identifying the presence of PFO in a MwA population, but TCD achieves better diagnostic performances. The NIRS provides additional information about the cerebral vasoreactivity and highlights substantial differences between patients with latent and permanent shunts that warrant further studies.

T05-O-12 Erectile dysfunction as early marker of cerebral ischemic damage. Is it useful performing neurological investigations?

Objective Erectile dysfunction (ED) is evidence of atherosclerosis and index of endothelial damage. Many authors demonstrated association with cardiovascular events and coronary artery diseases (CAD); the severity of ED was correlated with the angiographic extension of coronary atherosclerotic process. Few studies have given information about association between ED and subclinical cerebral ischaemic damage. This study was planned to test the hypothesis that patients with isolated ED, without signs of systemic and carotid atherosclerosis, compared to healthy population, have a reduced cerebral vasoreactivity ( CVR) as a marker of endothelial damage. Design and method 15 patients with erectile dysfunction (ED+ ) and 15 without erectile dysfunction(ED-) subjects, matched for age and vascular risk factors, were submitted to andrological and neurolological screening. Ecocolordoppler of cavernous arteries and nocturnal penil tumescence rigidometry were performed. Neurological assessment was performed by carotid duplex ultrasound and Transcranial Doppler and by assessing cerebrovascular reserve on both middle cerebral arteries calculating Vasomotor Reserve (VMR), after breath holding and hyperventilation. Results Carotid Duplex showed a light carotid stenosis in 3 patients: 2 in the ED+ and 1 in the ED-. No differences about intima-media thickness between ED+ and ED-. Slight slower mean middle cerebral arteries (MCA) flow velocities in ED+ in respect to ED -. ED+ showed a reduced VMR in respect to ED. Conclusions Reduced VRM in ED+ may represent a marker of early cerebral vasomotor dysfunction due to subclinical endothelial damage. So performing neurological investigations is unnecessary, but further studies about the relation between ED and cerebral ischaemic damage are needed.

Tissue Pulsatility Imaging of Cerebral Vasoreactivity During Hyperventilation

Tissue pulsatility imaging (TPI) is an ultrasonic technique that is being developed at the University of Washington to measure tissue displacement or strain as a result of blood flow over the cardiac and respiratory cycles. This technique is based in principle on plethysmography, an older nonultrasound technology for measuring expansion of a whole limb or body part due to perfusion. TPI adapts tissue Doppler signal processing methods to measure the “plethysmographic” signal from hundreds or thousands of sample volumes in an ultrasound image plane. This paper presents a feasibility study to determine if TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected transcranially through the temporal acoustic window from four subjects before, during and after voluntary hyperventilation. In each subject, decreases in tissue pulsatility during hyperventilation were observed that were statistically correlated with the subject's end-tidal CO 2 measurements. (E-mail: kucewicz@u.washington.edu)

Cerebrospinal fluid dynamics

The pathophysiology of hydrocephalus can be modelled and described in terms of altered biomechanical parameters. Shunting is aimed to correct the patient's cerebrospinal fluid dynamics, compensating for inadequate cerebrospinal fluid re-absorption or insufficient volume buffering reserve. Computerized infusion studies implement intracranial pressure and arterial pressure signal processing and model analysis to allow the estimation of cerebrospinal dynamics variables such as cerebrospinal fluid outflow resistance, brain compliance and pressure-volume index, estimated sagittal sinus pressure, cerebrospinal fluid formation rate, compensatory reserve and cerebral vasoreactivity. Infusion studies can assist in the prognostication of normal pressure hydrocephalus and in the diagnosis of idiopathic intracranial hypertension. The technique is also helpful in the assessment of shunt malfunction, including posture-related over-drainage and shunt obstruction.

Atorvastatin Therapy is Associated with Greater and Faster Cerebral Hemodynamic Response

Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imagings of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n=8) and placebo (n=7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.

Effect of chronic alcohol consumption on brain damage following transient focal ischemia

Chronic alcohol consumption impairs cerebral vasoreactivity, and thus, may result in an increase in ischemic brain damage. The goal of this study is to examine the influence of chronic alcohol consumption on transient focal ischemia-induced brain damage. Sprague–Dawley rats were divided into two groups, a control group and an alcohol group. Eight weeks after being fed a liquid diet with or without alcohol, responses of parietal pial arterioles to systemic hypoxia and hypercapnia were measured using a cranial window technique. In separate experiments, rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h under ketamine/xylazine or isoflurane anesthesia. Regional cerebral blood flow (rCBF) was monitored through a Laser–Doppler flow probe attached to the lateral aspect of the skull. Neurological evaluation and ischemic lesion were assessed 24 h after reperfusion. Dilation of pial arterioles in response to hypoxia and hypercapnia was significantly reduced in alcohol-fed rats. Alcohol-fed rats had significantly larger infarct volumes and worse neurological outcomes than non-alcohol-fed rats under ketamine/xylazine or isoflurane anesthesia. In addition, rCBF measurement indicated that alcohol-fed rats had less regulatory rebound increase in rCBF after the initial drop in rCBF at the onset of MCAO. Our findings suggest that chronic alcohol consumption exacerbates transient focal ischemia-induced brain damage. Increased ischemic brain damage during alcohol consumption may be related to an impaired cerebral vasoreactivity.