Cerebral Perfusion Deficits Research Articles

Acute Treatment with Candesartan Reduces Early Injury After Permanent Middle Cerebral Artery Occlusion

We have shown that reduction of blood pressure (BP) immediately after the onset of reperfusion reduced neurovascular damage and improved functional outcome after experimental cerebral ischemia and candesartan is particularly effective in improving long-term functional outcome. In this study, we sought to determine if early BP lowering with candesartan, in the presence of an occluded cerebral artery, will reduce injury and improve outcome after experimental stroke. Male Wistar rats underwent 24 h or 7 days of middle cerebral artery occlusion (MCAO). A single dose of 1 mg/kg candesartan was administered intravenously at 3 h after MCAO. Animals received neurobehavioral testing at 3 h, 24 h, and 7 days, and blood pressure was measured by telemetry. Animals had brain tissue collected for infarct size (24 h and 7 days), hemoglobin content, matrix metalloproteinase (MMP) activity, and vascular endothelial growth factor (VEGF) expression (24 h only). Candesartan significantly decreased blood pressure, infarct size (-20%; p=0.021), hemoglobin excess (-50%; p=0.0013), and edema (-35%; p=0.0005) at 24 h after MCAO. This resulted in a reduced cerebral perfusion deficit (p=0.034) in the ischemic hemisphere compared with saline and significantly improved Bederson scores and paw grasp. MMP-2, MMP-9, and VEGF were significantly increased by MCAO, but there were no differences between candesartan- and saline-treated animals. There were no significant differences in behavioral outcome at day 7. BP lowering with candesartan reduces early brain injury after experimental stroke even when the artery remains occluded. The early benefits were not sustained at 7 days, as seen in reperfused animals, however. The neuroprotection and neurorestorative properties of candesartan may occur by separate distinct mechanisms.

Cerebral diffusion and perfusion deficits in North Sea divers

Diving is associated with a risk of cerebral decompression illness, and the prevalence of neurological symptoms is higher in divers compared with control groups. Microvascular dysfunction due to gas microembolism and exposure to hyperoxia are possible mechanisms, which may result in cerebral diffusion and perfusion deficits. To investigate if possible functional derangements of the microvasculature and microstructure would be more prevalent among symptomatic divers. Magnetic resonance imaging (MRI) was performed in 91 former divers and 45 controls. Individual parametric images of apparent diffusion coefficient (ADC), cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were generated on the basis of diffusion- and perfusion-weighted imaging. To identify regions with statistically significant differences between groups (P < 0.05, corrected for false discovery rate), voxel-wise ANCOVA analysis was performed for each of the four parametric images. Significant regional group differences were found in all four parametric comparisons. Gross regional ADC differences were seen throughout the brain, including large frontal and temporal white-matter regions, the hippocampus, and parts of the cerebellum. Differences in the perfusion maps were localized in fewer and smaller clusters, including parts of the cerebellum, the putamen, and the anterior watershed regions. Regional functional abnormalities as measured by diffusion- and perfusion-weighted imaging were identified in the divers, and there was a partial co-localization of the regions identified in the perfusion and the diffusion images. The findings may explain some of the long-term clinical symptoms reported among professional divers.

Noninvasive Assessment of Cerebral Perfusion and Oxygenation in Acute Ischemic Stroke by Near-Infrared Spectroscopy

Background: In acute stroke patients, there is a need for noninvasive measurement to monitor blood flow-based therapies. We investigated the utility of near-infrared spectroscopy (NIRS) to determine cerebral perfusion in these patients. Methods: Eleven patients were investigated within 1.4 ± 2.2 days after onset of an ischemic middle cerebral artery infarction by monitoring the kinetics of an intravenous bolus of indocyanine green (ICG). For ICG kinetics, bolus peak time, time to peak (TTP = time between 0 and 100% ICG maximum), maximum ICG concentration, rise time (time between 10 and 90% ICG maximum), slope (maximum ICG/TTP), and blood flow index (BFI = maximum ICG/rise time) were obtained. Perfusion-weighted MRI (PWI) and NIRS measurements were performed within 24 h, and the interhemispherical differences of TTP values were compared. Results: Stroke patients showed an increased bolus peak time (p < 0.02), TTP (p < 0.01), and rise time (p < 0.01), whereas slope (p < 0.01) and BFI (p < 0.01) were diminished at the site of infarction as compared to the unaffected hemisphere. The interhemispherical differences of TTP as measured by PWI and NIRS were closely correlated (r = 0.86). Conclusions: Noninvasive measurements of cerebral ICG kinetics by NIRS provide a useful means of detecting cerebral perfusion deficits in patients with acute stroke, which correlate well with those obtained by PWI.

Microbubbles traversing the blood–brain barrier for imaging and therapy

In the last several years great progress has been made in the field of ultrasound perfusion imaging of the brain. Different approaches have been assessed and shown to be capable of early detection of cerebral perfusion deficits. Real-time low mechanical index imaging simplifies the acquisition of perfusion parameters and alleviates many of the previous imaging problems related to shadowing, uniplanar analysis, and temporal resolution. With the advent of this new, highly sensitive contrast-specific imaging technique new possibilities of real-time visualization of brain infarctions and cerebral hemorrhages have emerged. Microbubbles that traverse the blood-brain barrier (BBB) can also elicit bioeffects that may be used to open the BBB for targeted delivery of macromolecular agents to the brain. Possible ways in which substances cross the BBB after application of this novel approach include transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions, and free passage through injured endothelium. Although relatively little tissue damage occurs at low acoustic intensities capable of opening the BBB, no investigation has demonstrated a total lack of BBB injury when using ultrasound and microbubbles. Further studies are necessary to address the effects of ultrasound and microbubbles upon the various transport mechanisms of the BBB. Moreover, investigations aimed at elucidating how ultrasound and microbubbles interact at the molecular level of the BBB are necessary. Results of such studies will increase our understanding of the mechanisms of BBB opening and also allow a better appraisal of the safety of this technique for future clinical applications.

Impact of Fasting Glycemia and Regional Cerebral Perfusion in Diabetic Subjects

Diabetes mellitus increases the risk of ischemic stroke. The aim of this study was to investigate the correlation between fasting plasma glucose (FPG) and changes in regional cerebral perfusion (CP) in subjects with DM. CP was assessed in 24 subjects (mean age 44+/-2.5 years) with type 1 diabetes mellitus by single photon emission computed tomography. Analysis of CP during elevated FPG (224+/-24 mg/dL) showed 3 or more deficits in 42% of the subjects. A positive relationship between the number of CP deficits and FPG was observed (P<0.01), but not with age, sex, body mass index, or duration of diabetes mellitus. Regional deficits were reduced (P<0.001) with improvement in FPG (119+/-5 mg/dL). This reduction remained significant after adjustment for age, sex, and body mass index. Plasma levels of P-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, established markers of endothelial dysfunction, were significantly decreased with lower FPG. Furthermore, thiobarbituric acid reactive substance plasma levels, an index of oxidative stress, were also reduced (P<0.01). The present study demonstrates that changes in FPG are associated with functional changes in regional CP. Hyperglycemia-induced endothelial dysfunction may be implicated in the impaired regional CP of diabetic subjects.

EEG of chronic marijuana users during abstinence: Relationship to years of marijuana use, cerebral blood flow and thyroid function

Objective Marijuana abuse is associated with neurological changes including increases in frontal EEG alpha during abstinence. Research is needed to assess to what extent these EEG patterns are indicative of cerebral perfusion deficits. Methods We recorded the resting eyes closed EEG of 75 abstinent marijuana users and 33 control subjects. Fifty-six marijuana users used marijuana for less than eight years and 19 used for eight years or more. The EEG evaluation occurred within 72 h of admission to an inpatient unit. Fifty-nine marijuana users remained abstinent for a month and were tested twice. Supplemental psychological and physiological data were also collected. Results Log alpha2 and beta2 power at posterior sites were significantly lower for the marijuana abusers that used eight years or more than the other marijuana abusers and the control subjects. These EEG changes continued for the month of abstinence. The marijuana users who used marijuana for more than eight years, also, had lower heart rates and thyroid function (T4) compared to the other marijuana users and the control subjects. Conclusions Chronic marijuana use was also associated with reduced EEG power in alpha and beta bands at posterior sites. These reductions in EEG power appear to be related to cerebral perfusion deficits and/or thyroid function in marijuana abusers. Significance Our results suggest EEG, cerebral blood flow velocity, cardiovascular and thyroid function alterations in marijuana abuser with an extended period of use. These alterations reflect under arousal in these systems.

Regional cerebral blood flow in patients with sickle cell disease: study with single photon emission computed tomography

Neurological complications have been reported in patients with sickle-cell disease (SCD) using positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), but not with single photon emission computed tomography (SPECT). The objective of this study was to investigate brain perfusion in the patients with SCD using SPECT after technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO), was administered and compare the findings with those of demography, physical examination, MRI and hematological profile. The study involved 21 patients (12 males, 9 females, age at study 8-45 years) who were known to be having SCD for a duration of at least 5 years. The patients were not in acute crisis and had normal neurological assessments with no known history of stroke or transient ischemic episode or previous abnormal CT or MRI brain scan, and were right-handed. The brain SPECT was performed after intravenous injection of 740 MBq (20 mCi) 99mTc-HMPAO in adults or an appropriate dose in pediatric patients. The scans were visually interpreted by two nuclear medicine physicians and a decision was reached by consensus. An MRI done 3 months later was interpreted by a radiologist. The demographic data and hematological profile were obtained from the medical records of the patients. Of the 21 patients, 7 (age 11-22 years) had brain perfusion deficit mostly in the frontal lobe either alone or in combination with temporal and/or parietal lobe. The MRI was abnormal in 2 patients. The brain perfusion deficit was not associated with the demographic data of the patients or hematological profiles. The findings show that SPECT was useful in detecting brain perfusion deficit in SCD patients, and such an early detection may be clinically useful in the subsequent follow-up of such patients, since it is known that cerebral perfusion deficit can lead to silent infarct and/or overt stroke, and affect cognitive skills.

Ultrasound Perfusion Imaging: Determination of Thresholds for the Identification of Critically Disturbed Perfusion in Acute Ischemic Stroke—A Pilot Study

Ultrasound harmonic imaging of perfusion after ultrasound contrast agent (UCA) bolus injection (BHI) can detect cerebral perfusion deficits. In a pilot study, we evaluated the ability of time-intensity curve (TIC) measurements to differentiate between normal and hypoperfused brain areas in acute ischemic stroke. Ten patients with symptoms of acute middle cerebral artery infarction were investigated (SONOS 5500, Harmonic Imaging 1.6/3.8 MHz, diencephalic plane, 10 cm investigation depth, SonoVue 2.4 mL bolus). Peak signal increase (PSI), time-to-peak intensity (TPI) and area under the curve (AUC) were calculated for 60 regions-of-interest (ROIs) in each patient. Reference methods: Perfusion- and diffusion-weighted MRI (PWI/DWI) within 4 h before/after BHI (PWI threshold: 4 s). Receiver operating characteristics (ROC) analysis defined cut-off values for each TIC variable to distinguish between normal and affected brain areas as defined by PWI/DWI. In five patients, PWI showed a perfusion delay >4 s; seven patients had a DWI lesion. In three patients, both PWI and DWI findings showed pathology; one patient had a normal MRI of the insonation plane. Cut-off values for PWI delay: PSI: 5.53% (sensitivity .98, specificity .89); TPI: 4.04 s (sensitivity .74, specificity .69) and AUC: .63 (sensitivity .94, specificity .58). Referred to the mean value in unaffected brain areas the relative thresholds were 17.6%, 109.5% and 16.1%, respectively. Regarding DWI, only for PSI, a significant cut-off value was defined: 10.86%, sensitivity .84, specificity .60 (34.6% of mean). In conclusion, these thresholds distinguish between normal and affected brain areas in acute ischemic stroke. (E-mail: guenter.seidel@neuro.uni-luebeck.de)

On the Ability of Ultrasound Parametric Perfusion Imaging to Predict the Area of Infarction in AcuteIschemic Stroke

Cerebral perfusion deficits in acute ischemic stroke can be detected by means of transcranial harmonic imaging after ultrasound contrast agent bolus injection. We evaluated five different parameters of the bolus kinetics as parametric images and correlated areas of disturbed perfusion with the area of definite infarction. Perfusion harmonic imaging after SonoVue bolus injection (BHI) was used to investigate 22 patients suffering from acute internal carotid artery infarction. For each subject, we calculated five different images based on the following parameters from the time-intensity curve in each pixel: pixelwise peak intensity (PPI), area under the curve (AUC), positive gradient (PG), time to peak (TTP), and a three factor image from the factor analysis of medical image sequences (FAMIS). The findings in the diencephalic imaging plane were compared with the definite area of infarction, as diagnosed by cranial CT. In predicting the definite area of infarction in follow-up CT, we found the following sensitivities and positive predictive values (PPV): PPI (100 %/95 %), AUC (100 %/90 %), FAMIS (89 %/89 %), PG (84 %/94 %) and TTP (47 %/100 %). The areas of disturbed perfusion in all five types of parametric images correlated significantly with the area of infarction in CT. Images from the FAMIS algorithm and PPI images showed the highest Spearman rank correlation with the area of definite infarction as displayed in CT (both r = 0.76, p < 0.001). Images from the other parameters correlated as follows: PG: r = 0.62 (p = 0.003), AUC: r = 0.53 (p = 0.014), TTP: r = 0.50 (p = 0.021). BHI can detect disturbed perfusion in acute hemispheric stroke. In their ability to predict the development of an infarction, intensity-based parameters and FAMIS were determined to have a high sensitivity, and TTP was found to have a high PPV and specificity.

Valor da enolase específica do neurônio como indicador de prognóstico pós-parada cardiorrespiratória

Cardiac arrest is a state of severe cerebral perfusion deficit. Patients recovering from a cardiopulmonary resuscitation are at great risk of subsequent death or incapacitating neurologic injury, including persistent vegetative state. The early definition of prognosis for these patients has ethical and economic implications. The main purpose of this manuscript was to review the prognostic value of serum Neuron-Specific Enolase (NSE) in predicting outcomes in patients early after a cardiac arrest. Severe neurologic disability is the most feared complication after a cardiac arrest. Many studies are trying to find prognostic markers that can be associated with outcomes in patients surviving a cardiac arrest. Biochemical markers of neuronal injury seem to be promising in this scenario. Therefore, NSE levels have been studied in patients after a cardiac arrest and high enzyme levels suggest more extensive brain damage and are associated with unfavorable clinical outcomes. Outcome after a cardiac arrest is mostly determined by the degree of hypoxic brain damage and early determinations of serum NSE level can be a valuable ancillary method for assessing outcome in these patients.

Cerebral Ischemia-Hypoxia Induces Intravascular Coagulation and Autophagy

Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8). However, caspase-3 was not activated, and very few cells completed the apoptosis process. Instead, many damaged neurons showed features of autophagic/lysosomal cell death. At the tissue level, ischemia-hypoxia caused persistent cerebral perfusion deficits even after release of the carotid artery occlusion. These changes were associated with both platelet deposition and fibrin accumulation within the cerebral circulation and would be expected to contribute to infarction. Complementary studies in fibrinogen-deficient mice revealed that the absence of fibrin and/or secondary fibrin-mediated inflammatory processes significantly attenuated brain damage. Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain.

Brain SPECT study of common ground between hypothyroidism and depression

Hypothyroidism and major depressive disorder (MDD) share neuropsychiatric features. Cerebral perfusion deficits are found in both disorders. We compared regional cerebral blood flow (rCBF) in hypothyroidism and MDD to determine if clinical similarities are mediated by common neurocircuitry. Ten hypothyroid and 10 depressed patients underwent 99mTc-HMPAO-SPECT and clinical evaluation before and after response to respective treatments. Ten healthy controls underwent a similar, single, evaluation. Before treatment, rCBF in hypothyroid and depressed patients was lower than in controls, in posterior and anterior aspects of the brain respectively. rCBF in hypothyroidism was lower than in MDD in right posterior cingulate and parieto/occipital regions, and higher in frontal, prefrontal and sub-genual regions. Reduced rCBF in pre- and post-central gyri was found in both groups. Following treatment, rCBF in depressed patients increased and normalized, but remained unchanged in hypothyroidism. Affective symptoms in hypothyroidism may be mediated by neurocircuitry different from that of major depression.

Comparison of Asymmetry in Cerebral Blood Flow Between Brain Hemispheres Using Digital Subtraction Angiography

Recently, endovascular techniques have gained significant therapeutic potential for both treatment and prevention of stroke. Cerebral angiography, which is an essential component of these procedures, has been used to provide morphological information regarding condition of blood vessels. In this study, we propose to determine the possibility of acquiring information regarding cerebral blood flow (CBF) in addition to morphologic information from data routinely available during angiography. Digital subtraction angiography sequences were obtained for eight patients having occlusive disease in internal carotid artery (ICA) territories. Two regions-of-interest (ROIs) corresponding to the two brain hemispheres on AP view were delineated. For each image, the average pixel value within each ROI was calculated and used to generate time-density curves. Indices obtained from each curve were compared with each other and with the results obtained from the single photon emission computed tomography (SPECT) studies performed a pre- or postangiography procedure. Comparison between ICA stenosis and cerebral perfusion measurements revealed that cerebral perfusion deficit can be independent of arterial occlusive disease. The indices obtained from the time-density curves exhibit a correlating trend with the results from SPECT studies. However, lack of sufficient sample data prevented any meaningful statistical analysis to be conducted. We have developed a technique for utilizing the angiographic data for the important task of routinely and easily measuring CBF. Availability of CBF measurements during cerebral angiography may favorably impact upon the appropriate use of endovascular procedures and potentially contribute to the reduction of morbidity and mortality associated with stroke.

Transcranial Contrast Imaging of Cerebral Perfusion in Patients With Space-Occupying Intracranial Lesions

The aim of this study was to evaluate a deficit in cerebral perfusion after administration of the contrast agent SonoVue (Bracco Altana Pharma, Konstanz, Germany) in patients with intracranial space-occupying lesions. We used transcranial duplex sonography to examine 10 healthy volunteers and 4 patients. Of the patients, one 55-year-old woman had an intracranial glioblastoma; one 54-year-old woman had an intracranial hemorrhage; and one 49-year-old woman and one 69-year-old man had a malignant middle cerebral artery infarction. A decompressive craniectomy was performed in the 2 patients with malignant middle cerebral artery infarction. Triggered images with pulsing intervals of 1000 milliseconds were used for the evaluation of time-intensity curves in several regions of interest. The mechanical index was set at 1.6; in patients with a craniectomy, the mechanical index was set at 1.1. In all patients, the perfusion deficit could be recognized in the ipsilateral hemisphere. The superimposition of the sonographic images with those from computed tomography or magnetic resonance imaging showed a good correspondence in shape and size in patients with a craniectomy. In patients without a craniectomy, a rough correspondence with findings from magnetic resonance imaging or computed tomography could be recognized. By using contrast-enhanced transcranial duplex sonography, it is possible to image the perfusion deficit in cerebral microcirculation in patients with intracranial space-occupying lesions. These results should be confirmed by more pathologic cases and correlated with magnetic resonance imaging and other neuroimaging techniques. Additionally, further technical development in sonographic systems is necessary to improve the diagnostics of cerebral perfusion deficit.

Serum neuron-specific enolase as an early predictor of outcome after inhospital cardiac arrest

Cardiac arrest is a state of severe cerebral perfusion deficit. Patients recovering from a cardiopulmonary resuscitation are at great risk of subsequent death or incapacitating neurologic injury, including a persistent vegetative state. An early definition of neurologic prognosis for these patients has ethic and economic implications.

Evaluation of Cerebral Perfusion Deficit in Stroke Patients Using New Transcranial Contrast Imaging CPS™ Technology - Preliminary Results

Contrast-enhanced transcranial duplex sonography can be used to examine cerebral perfusion. This technique, however, is still faced with methodological problems. The aim of the present study is to evaluate cerebral perfusion deficit after administration of the contrast agent SonoVue in acute stroke patients using new contrast imaging software. Ten subjects (6 male stroke patients and 4 healthy volunteers), were examined using transcranial duplex sonography (Acuson Sequoia 512 Ultrasound System) after a bolus injection of the contrast agent SonoVue. The transcranial examination was performed using transient response harmonic grey scale imaging with refill kinetics. The Sequoia ultrasonographic system was equipped with a new contrast harmonic imaging software "Cadence contrast pulse sequencing technology" (CPS). Triggered images with the mechanical index (MI) at 1.1 as well as continuous registration with MI at 0.28 were used for the evaluation of time intensity curves in several regions of interest. The sonographically imaged hypoperfused areas were compared with findings from MR imaging. In all healthy volunteers, the contrast-enhanced signal could be recognized well in the ipsi- and also in the contralateral hemisphere up to the skull crown. In stroke patients, the perfusion deficit in the area of the MCA could be detected ipsilaterally in all subjects using triggered registration. Additionally, the area of MCA infarction could also be visualized in two patients using contralateral insonation. The low MI continuous imaging was successful in three patients. For all patients, the ischaemic region corresponded well in shape and size with the findings from MR imaging. CPS enhances the possibility of perfusion-imaging in cerebral microcirculation and of perfusion-deficit-imaging in patients with cerebral ischaemia. Further studies with a larger number of patients should be carried out to improve this method.

Short-term and long-term cognitive function and cerebral perfusion in off-pump and on-pump coronary artery bypass patients

The aim of this study was to evaluate cognitive function, as measured by serial neuropsychological testing, and cerebral perfusion, as measured by brain SPECT scanning in patients with coronary artery diseases (CAD) following off-pump and on-pump coronary artery bypass graft surgery. Besides, the relationship between cerebral blood flow, cognitive functions, surgery parameters, and cardiac function in these patients were estimated. Also, brain-protective effects of instenon were studied. Brain SPECT and comprehensive neuropsychological testing were performed 1 day before, 10-14 days and 6 months after coronary artery bypass graft surgery (CABG). The study involved 65 patients (62 males and 3 females, mean age 55+/-2) who underwent CABG with cardiopulmonary bypass (CPB) (43 pts) and off-pump coronary revascularization (OPCAB) using the Octopus stabilization system (22 pts). In 21 cases employing CPB, for prevention of the impairments of cerebral perfusion and cognitive deficit instenon was administered. CABG with the use of extracorporeal circulation is complicated by short-term and long-term neurocognitive dysfunction (in 96 and 55% cases, correspondingly). Also, in the early period after CABG, in 68% patients, decrease in regional cerebral blood flow (rCBF) was found, and after 6 months brain perfusion was lower than the baseline in 55% cases. Relationship between postoperative rCBF changes and the dynamics of cognitive function was found in early period and after 6 months following CABG. The coronary revascularization on beating heart or preventive administration of instenon in CPB patients helps significantly to diminish the risk of cerebrovascular complication.

Neuroimaging study of sex differences in the neuropathology of cocaine abuse

Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences. This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers. We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women. The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials. The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.

The role of ECA transection in the development of masticatory lesions in the MCAO filament model

In the intraluminal suture model of middle cerebral artery occlusion (MCAO) in the rat, lesions of the masticator muscles associated with impaired functional outcome occur. We evaluated the role of external carotid artery (ECA) transection. We assessed whether isolated interruption of an arterial or a venous connection to the ECA territory was sufficient to induce masticatory hypoperfusion and lesions. We also evaluated a direct access to the common carotid artery (CCA) with subsequent vascular closure with regard to its feasibility, frequency of masticatory lesions, complications, and cerebral ischemia. Cerebral and masticatory lesions and perfusion deficits were assessed by in vivo magnetic resonance imaging (MRI). Vessel patency was evaluated using computerized tomography angiography and histology. An interruption of arterial blood flow led to masticatory hypoperfusion. Masticatory lesions occurred in 6% of the rats. Access to and closure of the CCA were feasible in all animals, leading to moderate or severe vessel stenosis in 20%, and intraarterial thrombosis in 25% of the rats. Reproducible cerebral infarctions were obtained in all animals. In 24% of the rats, hyperintense MRI signal changes were observed in the ipsilateral temporal muscle. Thus, the induction of masticatory hypoperfusion and lesions by arterial transection supports the role of the ECA in this context. Direct access to the CCA with subsequent vessel closure led to stenosis in most animals. Preservation of ECA continuity was not suitable to fully prevent masticatory lesions.

Increased white matter hyperintensities in male methamphetamine abusers

Background The current study was conducted to compare the prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance (MR) imaging in methamphetamine (MA) abusers. Methods Thirty-three MA abusers and 32 age- and gender-matched healthy comparison subjects were studied. Axial T-2 weighted images and fluid attenuated inversion recovery axial images were obtained using 3.0 T MR scanner. The severity of WMH was assessed separately for deep and periventricular WMH. Ordinal logistic regression models were used to assess the odds ratio for WMH. Results MA abusers had greater severity of WMH than the healthy comparison subjects (odds ratio: 7.06, 8.46, and 4.56 for all, deep, and periventricular WMH, respectively). Severity of deep WMH correlated with total cumulative dose of MA ( p = 0.027). Male MA abusers had greater severity of WMH than female MA abusers (odds ratio = 10.00). While male MA abusers had greater severity of WMH than male comparison subjects (odds ratio = 18.86), there was no significant difference in WMH severity between female MA abusers and female comparison subjects. Conclusions The current study reports increased WMH in MA abusers, which may be related to MA-induced cerebral perfusion deficits. In addition, female MA abusers had less severe WMH than male MA abusers, possibly due to estrogen's protective effect against ischemic or neurotoxic effects of MA.