Alterations In Cerebral Blood Flow Research Articles

Transient cerebral hypoperfusion and hypertensive events during atrial fibrillation: a plausible mechanism for cognitive impairment.

Atrial fibrillation (AF) is associated with an increased risk of dementia and cognitive decline, independent of strokes. Several mechanisms have been proposed to explain this association, but altered cerebral blood flow dynamics during AF has been poorly investigated: in particular, it is unknown how AF influences hemodynamic parameters of the distal cerebral circulation, at the arteriolar and capillary level. Two coupled lumped-parameter models (systemic and cerebrovascular circulations, respectively) were here used to simulate sinus rhythm (SR) and AF. For each simulation 5000 cardiac cycles were analyzed and cerebral hemodynamic parameters were calculated. With respect to SR, AF triggered a higher variability of the cerebral hemodynamic variables which increases proceeding towards the distal circulation, reaching the maximum extent at the arteriolar and capillary levels. This variability led to critical cerebral hemodynamic events of excessive pressure or reduced blood flow: 303 hypoperfusions occurred at the arteriolar level, while 387 hypertensive events occurred at the capillary level during AF. By contrast, neither hypoperfusions nor hypertensive events occurred during SR. Thus, the impact of AF per se on cerebral hemodynamics candidates as a relevant mechanism into the genesis of AF-related cognitive impairment/dementia.

Actualización en la fisiopatología de la hidrocefalia crónica del adulto idiopática: ¿nos enfrentamos a otra enfermedad neurodegenerativa?

IntroductionSince its description five decades ago, the pathophysiology of idiopathic chronic adult hydrocephalus (iCAH) has been traditionally related to the effect that ventricular dilatation exerts on the structures surrounding the ventricular system. However, altered cerebral blood flow, especially a reduction in the CSF turnover rate, are starting to be considered the main pathophysiological elements of this disease. DevelopmentCompression of the pyramidal tract, the frontostriatal and frontoreticular circuits, and the paraventricular fibres of the superior longitudinal fasciculus have all been reported in iCAH. At the level of the corpus callosum, gliosis replaces a number of commissural tracts. Cerebral blood flow is also altered, showing a periventricular watershed region limited by the subependymal arteries and the perforating branches of the major arteries of the anterior cerebral circulation. The CSF turnover rate is decreased by 75%, leading to the reduced clearance of neurotoxins and the interruption of neuroendocrine and paracrine signalling in the CSF. ConclusionsiCAH presents as a complex nosological entity, in which the effects of subcortical microangiopathy and reduced CSF turnover play a key role. According to its pathophysiology, it is simpler to think of iCAH more as a neurodegenerative disease, such as Alzheimer disease or Binswanger disease than as the classical concept of hydrocephalus

Enhanced brainstem cerebral blood flow accompanies symptoms of anhedonia in young adults

Study: Midbrain serotonergic projections are of crucial theoretical significance for mood disorders. Furthermore, learned helplessness (LH) is associated with enhanced metabolic activity in rodent serotonergic midbrain models. However, little evidence supports serotonergic projections in predicting illness severity. We employed arterial spin labeling (ASL) to measure whole brain cerebral blood flow (CBF) in distressed and healthy individuals varying in anxiety and anhedonia. Methods: 36 distressed (27 females; mean age=22.2, SD=2.1) and 34 healthy (19 females; mean age=21.5, SD=1.8) individuals underwent a resting acquisition. Blood flow was measured using a multiband pseudo continuous ASL sequence. Regional cerebral perfusion data was collected with 25 slices, multiband factor=5, 4mm slick thickness, FA=90, 64x64 resolution, FOV=192x912, TR/TE=3.5s/19ms, labeling time=1.5s and postlabeling delay=1.7s. Anhedonia was measured using the Mood and Anxiety Symptom Questionnaire Anhedonic Depression Scale (MASQ-ADS), with the Snaith–Hamilton Pleasure Scale (SHAPS) as a secondary measure. Anxiety was measured using the MASQ General Distress Anxious Symptoms Scale. Anhedonia, anxiety and group were included in the regression model. Results: Anhedonia (MASQ-ADS) was associated with increased CBF in the midbrain (T=5.24, p_FWE=0.033), proximal to putative locations of the dorsal/median raphe nuclei (-12, -34, -26). Similar, although weaker, findings were observed with the SHAPS. Conclusion: Anhedonia is associated with altered CBF in the midbrain in a young adult population showing heterogeneous symptoms of distress. Significance: ASL may provide a particularly promising tool to examine enhanced local perfusion, potentially reflecting underlying midbrain serotonergic activity, which is predicted on the basis of LH studies in rodents but has thus far been difficult to investigate in humans.

Perfusion Deficits and Functional Connectivity Alterations in Memory-Related Regions of Patients with Post-Traumatic Stress Disorder.

To explore the potential alterations in cerebral blood flow (CBF) and functional connectivity of recent onset post-traumatic stress disorder (PTSD) induced by a single prolonged trauma exposure, we recruited 20 survivors experiencing the same coal mining flood disaster as the PTSD (n = 10) and non-PTSD (n = 10) group, respectively. The pulsed arterial spin labeling (ASL) images were acquired with a 3.0T MRI scanner and the partial volume (PV) effect in the images was corrected for better CBF estimation. Alterations in CBF were analyzed using both uncorrected and PV-corrected CBF maps. By using altered CBF regions as regions-of-interest, seed-based functional connectivity analysis was then performed. While only one CBF deficit in right corpus callosum of PTSD patients was detected using uncorrected CBF, three more regions (bilateral frontal lobes and right superior frontal gyrus) were identified using PV-corrected CBF. Furthermore, the regional CBF of right superior frontal gyrus exhibited significantly negative correlation with the symptom severity (r = −0.759, p = 0.018). The resting-state functional connectivity analysis revealed increased connectivity between left frontal lobe and right parietal lobe. The results indicated the symptom-specific perfusion deficits and an aberrant connectivity in memory-related regions of PTSD patients when using PV-corrected ASL data. It also suggested that PV-corrected CBF exhibits more subtle changes that may be beneficial to perfusion and connectivity analysis.

Chronic cerebrovascular dysfunction after traumatic brain injury.

Traumatic brain injuries (TBI) often involve vascular dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of cerebrovascular dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation. We also discuss the mechanisms that mediate these dysfunctions, focusing on the cellular components of cerebral blood vessels (endothelial cells, smooth muscle cells, astrocytes, pericytes, perivascular nerves) and their known and potential roles in the secondary injury cascade. © 2016 Wiley Periodicals, Inc.

Magnetic resonance imaging arterial-spin-labelling perfusion alterations in childhood migraine with atypical aura: a case-control study.

Atypical migraine with aura can be challenging to diagnose. Arterial-spin-labelling (ASL) is able to non-invasively quantify brain perfusion. Our aim was to report cerebral blood flow (CBF) alterations using ASL, at the acute phase of atypical migraine with aura in children. Paediatric patients were retrospectively included if (1) referred for acute neurological deficit(s), (2) underwent brain magnetic resonance imaging (MRI) at presentation with ASL sequence, and (3) had subsequent diagnosis of migraine with aura. Neurological symptom-free controls were matched for age. Twenty-eight regions of interest (ROIs) were drawn on CBF maps for each participant/control. Ten patients were included (median age 13y, range 8-16y). Eight of 10 had multiple aura symptoms during the episode. For every patient, CBF was decreased in a brain region consistent with symptoms when MRI was performed less than 14 hours after onset (n=7 patients) and increased if the MRI was performed 17 hours or more after (n=4 MRIs). MRI-ASL appears to be a promising tool for the diagnostic workup and differentials exclusion in paediatric migraine with aura. Constant and time-consistent non-territorial CBF modifications were found in our sample providing additional insight to migraine with aura pathophysiology. The authors encourage implementing this sequence at the acute phase of unexplained paediatric neurological deficits, with or without accompanying headache.

Monitoring of cerebral blood flow during hypoxia-ischemia and resuscitation in the neonatal rat using laser speckle imaging.

Neonatal hypoxic‐ischemic encephalopathy (HIE) is associated with alterations in cerebral blood flow (CBF) as a result of perinatal asphyxia. The extent to which CBF changes contribute to injury, and whether treatments that ameliorate these changes might be neuroprotective, is still unknown. Higher throughput techniques to monitor CBF changes in rodent models of HIE can help elucidate the underlying pathophysiology. We developed a laser speckle imaging (LSI) technique to continuously monitor CBF in six postnatal‐day 10 (P10) rats simultaneously before, during, and after unilateral hypoxia‐ischemia (HI, ligation of the left carotid artery followed by hypoxia in 8% oxygen). After ligation, CBF to the ligated side fell by 30% compared to the unligated side (P < 0.0001). Hypoxia induced a bilateral 55% reduction in CBF, which was partially restored by resuscitation. Compared to resuscitation in air, resuscitation in 100% oxygen increased CBF to the ligated side by 45% (P = 0.033). Individual variability in CBF response to hypoxia between animals accounted for up to 24% of the variability in hemispheric area loss to the ligated side. In both P10 and P7 models of unilateral HI, resuscitation in 100% oxygen did not affect hemispheric area loss, or hippocampal CA1 pyramidal neuron counts, after 1‐week survival. Continuous CBF monitoring using LSI in multiple rodents simultaneously can screen potential treatment modalities that affect CBF, and provide insight into the pathophysiology of HI.

Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence.

Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities. Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments.

Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer's Disease.

Alzheimer's disease is the most frequent type of dementia and diagnosed late in the progression of the illness when irreversible brain tissue loss has already occurred. For this reason, treatments have been ineffective. It is imperative to find novel therapies ameliorating modifiable risk factors (hypertension, stroke, diabetes, chronic kidney disease, and traumatic brain injury) and effective against early pathogenic mechanisms including alterations in cerebral blood flow leading to poor oxygenation and decreased access to nutrients, impaired glucose metabolism, chronic inflammation, and glutamate excitotoxicity. Angiotensin II receptor blockers (ARBs) fulfill these requirements. ARBs are directly neuroprotective against early injury factors in neuronal, astrocyte, microglia, and cerebrovascular endothelial cell cultures. ARBs protect cerebral blood flow and reduce injury to the blood brain barrier and neurological and cognitive loss in animal models of brain ischemia, traumatic brain injury, and Alzheimer's disease. These compounds are clinically effective against major risk factors for Alzheimer's disease: hypertension, stroke, chronic kidney disease, diabetes and metabolic syndrome, and ameliorate age-dependent cognitive loss. Controlled studies on hypertensive patients, open trials, case reports, and database meta-analysis indicate significant therapeutic effects of ARBs in Alzheimer's disease. ARBs are safe compounds, widely used to treat cardiovascular and metabolic disorders in humans, and although they reduce hypertension, they do not affect blood pressure in normotensive individuals. Overall, there is sufficient evidence to consider long-term controlled clinical studies with ARBs in patients suffering from established risk factors, in patients with early cognitive loss, or in normal individuals when reliable biomarkers of Alzheimer's disease risk are identified.

Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study.

ObjectiveFrontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modifying agents, the development of sensitive biomarkers to evaluate such agents in the earliest stage of FTD is crucial. In the current longitudinal study we used arterial spin labeling MRI (ASL) in presymptomatic carriers of MAPT and GRN mutations to investigate early changes in cerebral blood flow (CBF).MethodsHealthy first-degree relatives of patients with a MAPT or GRN mutation underwent ASL at baseline and follow-up after two years. We investigated cross-sectional and longitudinal differences in CBF between mutation carriers (n = 34) and controls without a mutation (n = 31).ResultsGRN mutation carriers showed significant frontoparietal hypoperfusion compared with controls at follow-up, whereas we found no cross-sectional group differences in the total study group or the MAPT subgroup. Longitudinal analyses revealed a significantly stronger decrease in CBF in frontal, temporal, parietal, and subcortical areas in the total group of mutation carriers and the GRN subgroup, with the strongest decrease in two mutation carriers who converted to clinical FTD during follow-up.InterpretationWe demonstrated longitudinal alterations in CBF in presymptomatic FTD independent of grey matter atrophy, with the strongest decrease in individuals that developed symptoms during follow-up. Therefore, ASL could have the potential to serve as a sensitive biomarker of disease progression in the presymptomatic stage of FTD in future clinical trials.

Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging.

Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning.

Alterations of ASL Blood Perfusion in the Thalamus and Ventral Intermediate Thalamic Nucleus in Parkinson’s Disease Patients

Parkinson’s disease (PD) is characterized by brain metabolic abnormalities, particularly in subcortical regions. However, previously reported observations of subcortical blood perfusion are inconsistent, especially in the thalamus. This study aimed to investigate the alterations of thalamic regional cerebral blood flow (CBF) in PD by using a recently developed advanced 3D pseudo-continuous pulse arterial spin labeling (ASL) perfusion magnetic resonance imaging approach. Twenty-three PD patients with mild-to-moderate stage disease and 29 normal control subjects underwent ASL MRI. Regional mean CBF values in the thalamus and ventral intermediate thalamic nucleus (Vim) were measured and compared between the groups by one-way analysis of variance. The PD patients showed significantly lower CBF than controls in the bilateral thalamus and Vim. Our findings indicate that hypoperfusion in the thalamus and Vim could be an imaging marker of PD.

Neurodevelopmental delay in pediatric HIV/AIDS: current perspectives

The effects of HIV on the developing nervous system of perinatally HIV (PHIV)- infected children are substantial, yet poorly understood. While the introduction of combination antiretroviral therapy (cART) reduced the prevalence of HIV encephalopathy, many cART- treated PHIV-infected children still present with neurodevelopmental delays and cognitive impairment. The underlying pathogenesis may partially differ from that in adults, as HIV not only causes direct injury to the central nervous system (CNS) but may also impede the development of the pediatric brain. Increasing evidence implies significant roles for ongo - ing neuroinflammation, vascular dysfunction and hypercoagulability induced by HIV despite adequate viral suppression. Subsequent manifestations of HIV in the pediatric brain include gray-matter volume reduction, white-matter lesions, and basal ganglia calcifications, but even in the absence of such macrostructural changes, the detrimental effects of HIV are clearly revealed in widespread microstructural changes, such as poorer white-matter integrity and alterations in cerebral metabolites and blood flow. Viral suppression on cART evidently does not fully protect against cerebral injury, but knowledge concerning the pharmacokinetics and toxicity of cART in the pediatric CNS is lacking. Investigations combining neuropsychological assessment, multimodal neuroimaging, and laboratory evaluation of inflammatory and neurodegenerative markers could greatly increase our understanding of the pathogenesis of HIV in the developing nervous system and improve treatment and prevention strategies. Longitudinal research will be crucial to observe the long-term consequences of CNS exposure to HIV and cART in PHIV- infected children as they survive into adulthood.

Is dexmedetomidine a favorable agent for cerebral hemodynamics?

Is dexmedetomidine a favorable agent for cerebral hemodynamics?

Cerebral blood flow monitoring

AbstractBrain is a unique organ of the body that receives highest amount of cardiac output and totally depend on the blood supply for its survival and no reserve of blood flow making it vulnerable for ischaemia. Other important properties of cerebral circulation include autoregulation of blood flow, high oxygen extraction, and selective increase in blood flow to specific brain areas during various functional activities. It is important to understand that systemic and local factors affect the cerebral blood flow and the brain functions. Moreover the alterations in cerebral blood flow (acute or chronic) can be responsible for various symptoms as well as diseases pertaining to the brain. Hence it is important to measure the cerebral blood flow for the diagnostic as well as therapeutic purpose. This review focusses on the various techniques available for monitoring the cerebral blood flow.

Blood Pressure is Associated With Cerebral Blood Flow Alterations in Patients With T2DM as Revealed by Perfusion Functional MRI

Type 2 diabetes mellitus (T2DM) and hypertension are both associated with cognitive impairment and brain function abnormalities. We investigated whether abnormal cerebral blood flow (CBF) patterns exists in T2DM patients and possible relationships between aberrant CBF and cognitive performance. Furthermore, we examined the influence of hypertension on CBF alterations in T2DM patients.T2DM patients (n = 38) and non-T2DM subjects (n = 40) were recruited from clinics, hospitals, and normal community health screenings. Cerebral blood flow images were collected and analyzed using arterial spin labeling perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between T2DM patients and non-T2DM controls were detected via 1-way ANOVA. The interaction effects between hypertension and T2DM for CBF alterations were also examined. Correlation analyses illustrated the association between CBF values and cognitive performance and between CBF and blood pressure.Compared with non-T2DM controls, T2DM patients exhibited decreased CBF, primarily in the visual area and the default mode network (DMN); decreased CBF in these regions was correlated with cognitive performance. There was a significant interaction effect between hypertension and diabetes for CBF in the precuneus and the middle occipital gyrus. Additionally, blood pressure correlated negatively with CBF in T2DM patients.T2DM patients exhibited reduced CBF in the visual area and DMN. Hypertension may facilitate a CBF decrease in the setting of diabetes. T2DM patients may benefit from blood pressure control to maintain their brain perfusion through CBF preservation.

Cerebral Blood Flow Alterations in Acute Sport-Related Concussion.

Sport-related concussion (SRC) is a major health problem, affecting millions of athletes each year. While the clinical effects of SRC (e.g., symptoms and functional impairments) typically resolve within several days, increasing evidence suggests persistent neurophysiological abnormalities beyond the point of clinical recovery after injury. This study aimed to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared CBF maps assessed in 18 concussed football players (age, 17.8 ± 1.5 years) obtained within 24 h and at 8 days after injury with a control group of 19 matched non-concussed football players. While the control group did not show any changes in CBF between the two time-points, concussed athletes demonstrated a significant decrease in CBF at 8 days relative to within 24 h. Scores on the clinical symptom (Sport Concussion Assessment Tool 3, SCAT3) and cognitive measures (Standardized Assessment of Concussion [SAC]) demonstrated significant impairment (vs. pre-season baseline levels) at 24 h (SCAT, p < 0.0001; SAC, p < 0.01) but returned to baseline levels at 8 days. Two additional computerized neurocognitive tests, the Automated Neuropsychological Assessment Metrics and Immediate Post-Concussion and Cognitive Testing, showed a similar pattern of changes. These data support the hypothesis that physiological changes persist beyond the point of clinical recovery after SRC. Our results also indicate that advanced ASL MRI methods might be useful for detecting and tracking the longitudinal course of underlying neurophysiological recovery from concussion.

Abstract 19451: Preoperative Brain MRI Findings in d-Transposition of the Great Arteries and Relation to Timing of Diagnosis

Introduction: Congenital heart disease is known to be associated with alterations in fetal cerebral blood flow and brain development. Instability in the fetal/neonatal periods may lead to injury. We sought to assess the prevalence of preoperative brain injury in neonates with d-transposition of the great arteries (d-TGA) and the relationship to prenatal/postnatal variables and outcomes. Methods: We performed a single center retrospective analysis of neonates with d-TGA who had preoperative brain MRI from 2009-2014. Patients with other cardiac and/or extracardiac anomalies were excluded. Prenatal/postnatal clinical variables were recorded and correlated to brain MRI findings. Results: A total of 45 neonates with d-TGA were identified of which 23 (51%) were diagnosed prenatally. The average gestational age was 38 weeks (range 33-41). All underwent an arterial switch procedure with 100% survival. Those diagnosed prenatally were more likely to be born within 5 miles of the tertiary pediatric center (96% vs. 5%, p&lt;0.001), had lower incidence of hypoxia (lowest PaO2 25.3 vs 21.1, p=0.02), shorter time to cardiac intensive care unit admission (85 vs 1025 minutes, p=0.002), and shorter time to balloon atrial septostomy (295 vs 1456 minutes, p=0.007). Brain MRI was abnormal in 14 (31%); 9/23 (39%) with a prenatal and 5/22 (23%) with a postnatal diagnosis. The most common abnormality was small or punctate ischemic white matter lesions (N=14). Three patients had evidence of deep grey matter injury. Those with brain MRI abnormalities had a lower average gestational age (37 vs 39 weeks, p=0.02) and were less likely to have had a balloon atrial septostomy (79% vs 93%, p=0.03). Brain MRI findings were not associated with preoperative acidosis, hypoxia, need for inotropes, time to admission to cardiac intensive care unit, or surgical procedural variables. Conclusions: Neonates with d-TGA had similar incidence of preoperative brain injury by MRI whether diagnosed pre or postnatally. Brain injury was associated with lower gestational age and lack of balloon septostomy. Further work is needed to determine any association between prenatal diagnosis and type/severity of brain injury, as well as other in utero factors relating to brain development that may play a role.

Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment.

To determine whether cortical β-amyloid (Aβ) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI). Forty participants with aMCI were included in this study. Cortical Aβ depositions were measured by (18)F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum. Circadian BP profiles were measured by 24-hour ambulatory monitoring during awake and sleep periods. The dipping status of sleep BP (i.e., the percent changes from the awake BP) was calculated and dichotomized into the dipper (≥10%) and nondipper (<10%) groups. Dynamic CBF regulation was assessed by a transfer function analysis between beat-to-beat changes in BP and CBF velocity measured from the middle cerebral artery during a repeated sit-stand maneuver. Age was positively correlated with a greater Aβ deposition in the posterior cingulate, precuneus, and mean cortex. Accounting for the age effect, attenuated reductions in sleep systolic BP were associated with higher levels of posterior cingulate SUVR. Consistently, the nondippers exhibited a higher SUVR in the posterior cingulate than the dippers. Transfer function gain between changes in BP and CBF velocity was diminished in the nondippers, and moreover those individuals with a lower gain exhibited a higher SUVR in the posterior cingulate. Attenuated reductions in sleep BP are associated with a greater Aβ burden in the posterior cingulate and altered dynamic CBF regulation in patients with aMCI.

Cannabinoid receptor activation in the juvenile rat brain results in rapid biomechanical alterations: Neurovascular mechanism as a putative confounding factor

We have recently reported cannabinoid-induced rapid changes in the structure of individual neurons. In order to investigate the presence of similar effects at the regional level, measures of brain tissue biomechanics are required. However, cannabinoids are known to alter cerebral blood flow (CBF), putatively resulting in presently unexplored changes in cerebral tissue biomechanics. Here we used magnetic resonance elastography (MRE) and flow-sensitive alternating inversion recovery (FAIR) imaging to measure in vivo alterations of mechanical properties and CBF, respectively, in the rat hippocampus, a brain region with a high density of type-1 cannabinoid receptors (CB1R). Systemic injection of the cannabinoid agonist CP55,940 (0.7 mg/kg) induced a significant stiffness decrease of 10.5 ± 1.2% at 15 minutes. FAIR imaging indicated a comparable decrease (11.3 ± 1.9%) in CBF. Both effects were specific to CB1R activation, as shown by pretreatment with the CB1R-specific antagonist AM251. Strikingly, similar rapid parallel changes of brain elasticity and CBF were also observed after systemic treatment with the hypotensive drug nicardipine. Our results reveal important drug-induced parallel changes in CBF and brain mechanical characteristics, and show that blood flow-dependent tissue softening has to be considered as an important putative confounding factor when cerebral viscoelastic changes are investigated.