Cortical Cerebral Blood Flow Research Articles

Hypertension and cerebral blood flow in the development of Alzheimer's disease.

We investigated the interactive associations between amyloid and hypertension on the entorhinal cortex (EC) tau and atrophy and the role of cerebral blood flow (CBF) as a shared mechanism by which amyloid and hypertension contribute to EC tau and regional white matter hyperintensities (WMHs). We analyzed data from older adults without dementia participating in the Add-Tau study (NCT02958670, n=138) or Alzheimer's Disease Neuroimaging Initiative (ADNI) (n=523) who had available amyloid-positron emission tomography (PET), tau-PET, fluid-attenuated inversion recovery (FLAIR), and T1-weighted magnetic resonance imaging (MRI). A subsample in both cohorts had available arterial spin labeling (ASL) MRI (Add-Tau: n=78; ADNI: n=89). The detrimental effects of hypertension on AD pathology and EC thickness were more pronounced in the Add-Tau cohort. Increased amyloid burden was associated with decreased occipital gray matter CBF in the ADNI cohort. In both cohorts, lower regional gray matter CBF was associated with higher EC tau and posterior WMH burden. Reduced cerebral perfusion may be one common mechanism through which hypertension and amyloid are related to increased EC tau and WMH volume. Hypertension is associated with increased entorhinal cortex (EC) tau, particularly in the presence of amyloid. Decreased cortical cerebral blood flow (CBF) is associated with higher regional white matter hyperintensity volume. Increasing amyloid burden is associated with decreasing CBF in the occipital lobe. MTL CBF and amyloid are synergistically associated with EC tau.

The Combination of Presurgical Cortical Gray Matter Volumetry and Cerebral Perfusion Improves the Efficacy of Predicting Postoperative Cognitive Impairment of Elderly Patients.

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.

Diagnostic accuracy of arterial spin labeling MR imaging in detecting cerebral arteriovenous malformations: a systematic review and meta-analysis.

Diagnostic accuracy of arteriovenous malformations (AVMs) is imperative for delineating management. The current standard is digital subtraction angiography (DSA). Arterial spin labeling (ASL) is an understudied noninvasive, non-contrast technique that allows angioarchitecture visualization and additionally quantifies cortical and AVM cerebral blood flow and hemodynamics. This meta-analysis aims to compare ASL and DSA imaging in detecting and characterizing cerebral AVMs. EMBASE, Medline, Scopus, and Cochrane databases were queried from inception to July 2022 for reports of AVMs evaluated by DSA and ASL imaging. Fourteen studies with 278 patients evaluated using DSA and ASL imaging prior to intervention were included; pCASL in 11 studies (n = 239, 85.37%) and PASL in three studies (n = 41, 14.64%). The overall AVM detection rate on ASL was 99% (CI 97-100%); subgroup analysis revealed no difference between pCASL vs. PASL (99%; CI 96-100% vs. 100%; CI 95-100% respectively, p = 0.42). The correlation value comparing ASL and DSA nidus size was 0.99. DSA and ASL intermodality agreement Cohen's k factor for Spetzler Martin Grading (SMG) was reported at a median of 0.98 (IQR 0.73-0.1), with a 1.0 agreement on SMG classification. A median of 25 arteries were detected by DSA (IQR 14.5-27), vs. 25 by ASL (IQR 14.5-27.5) at a median 0.92 k factor. ASL provides angioarchitectural visualization noninferior to DSA and additionally quantifies CBF. Our study suggests that ASL should be considered in the detection of AVMs, especially in patients with contrast contraindications or apprehension towards an invasive assessment.

Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

Objective To investigate the role of sea-level cerebral blood flow (CBF) in predicting acute mountain sickness (AMS) using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging (MRI) including 3D-pCASL at sea level. The CBF values of the bilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), and posterior inferior cerebellar artery (PICA) territories and the laterality index (LI) of CBF were compared between the AMS and non-AMS groups. Statistical analyses were performed to determine the relationship between CBF and AMS, and the predictive performance was assessed using receiver operating characteristic (ROC) curves.Results The mean cortical CBF in women (81.65 ± 2.69 mL/100 g/min) was higher than that in men (74.35 ± 2.12 mL/100 g/min) (P < 0.05). In men, the cortical CBF values in the bilateral ACA, PCA, PICA, and right MCA were higher in patients with AMS than in those without. Cortical CBF in the right PCA best predicted AMS (AUC = 0.818). In women, the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753.Conclusion Although the mechanism and prediction of AMS are quite complicated, higher cortical CBF at sea level, especially the CBF of the posterior circulatory system, may be used for prediction in male volunteers using non-invasive 3D-pCASL.

Preliminary investigations into human neurofluid transport using multiple novel non-contrast MRI methods.

We discuss two potential non-invasive MRI methods to study phenomena related to subarachnoid cerebrospinal fluid (CSF) motion and perivascular fluid transport, and their association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient, D*, or CSF movement across large spaces like the subarachnoid space (SAS). We also performed perfusion-based multi-echo, Hadamard encoded arterial spin labeling (ASL) to evaluate whole brain cortical cerebral blood flow (CBF) and trans-endothelial exchange (Tex) of water from the vasculature into the perivascular space and parenchyma. Both methods were used in young adults (N = 9, 6 F, 23 ± 3 years old) in the setting of sleep and sleep deprivation. To study aging, 10 older adults (6 F, 67 ± 3 years old) were imaged after a night of normal sleep and compared with the young adults. D* in SAS was significantly (p < 0.05) reduced with sleep deprivation (0.016 ± 0.001 mm2/s) compared to normal sleep (0.018 ± 0.001 mm2/s) and marginally reduced with aging (0.017 ± 0.001 mm2/s, p = 0.029). Cortical CBF and Tex were unchanged with sleep deprivation but significantly lower in older adults (37 ± 3 ml/100 g/min, 578 ± 61 ms) than in young adults (42 ± 2 ml/100 g/min, 696 ± 62 ms). IVIM was sensitive to sleep physiology and aging, and multi-echo, multi-delay ASL was sensitive to aging.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5T or 3T. Healthy controls were investigated with both 1.5T and 3T ASL-MRI. We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56years, range 18-82years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50years, range 21-77years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2mL/100g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Chronic hypertension alters the relationship between collateral blood flow, cortical cerebral blood flow, and brain tissue oxygenation.

This study measured the relationship between pial collateral (leptomeningeal anastomoses, LMA) flow, intraparenchymal cortical cerebral blood flow (cCBF) and brain tissue oxygenation (btO2) during acute ischemic stroke to investigate how pial flow translates to downstream cCBF and btO2 and examined how this relationship is altered in hypertension. Proximal transient middle cerebral artery occlusion (tMCAO) was performed in male Wistar (n = 8/group) and Spontaneously Hypertensive Rats (SHR, n = 8/group). A combination laser Doppler-oxygen probe was placed within the expected cortical peri-infarct in addition to a surface laser doppler probe which measured LMA flow. Phenylephrine (PE) was infused 30 minutes into tMCAO to increase blood pressure (BP) by 30% for 10 minutes and assessed CBF autoregulation. During the initial 30-minute period of tMCAO, btO2 and cCBF were lower in SHR compared to Wistar rats (btO2: 11.5 ± 10.5 vs 17.5 ± 10.8 mmHg and cCBF: -29.7 ± 23.3% vs -17.8 ± 41.9%); however, LMA flow was similar between groups. The relationship between LMA flow, cCBF and btO2 were interdependent in Wistar rats. However, this relationship was disrupted in SHR rats and partially restored by induced hypertension. This study provides evidence that cCBF and btO2 were diminished during tMCAO in chronic hypertension, and that induced hypertension was beneficial regardless of hypertensive status.

Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice

Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the modulation of cortical NVC and cerebral blood flow (CBF). Raphe serotonergic neurons were optogenically activated for 30 s, which immediately awakened the mice from non-rapid eye movement sleep. This caused a biphasic cortical hemodynamic change: a transient increase for a few seconds immediately after photostimulation onset, followed by a large progressive decrease during the stimulation period. Serotonergic neuron activation increased intracellular Ca2+ levels in cortical pyramidal neurons and astrocytes, demonstrating its effect on the NVC components. Pharmacological inhibition of cortical neuronal firing activity and astrocyte metabolic activity had small hypovolemic effects on serotonin-induced biphasic CBF changes, while blocking 5-HT1B receptors expressed primarily in cerebral vasculature attenuated the decreasing CBF phase. This suggests that serotonergic neuron activation leading to animal awakening could allow the NVC to exert a hyperemic function during a biphasic CBF response, with a predominant decrease in the cortex.

Diurnal variation of cerebral blood flow in healthy humans under normal entrained conditions.

The presence of a circadian cycle of cerebral blood flow may have implications for the occurrence of daily variations in cerebrovascular events in humans, but how cerebral blood flow varies throughout the day and its mechanism are still unclear. The study aimed to explore the diurnal variation of cerebral blood flow in healthy humans and its possible mechanisms. Arterial spin labelling images were collected at six time-points (09:00 hours, 13:00 hours, 17:00 hours, 21:00 hours, 01:00 hours, 05:00 hours) from 18 healthy participants (22-39 years old; eight females) to analyse diurnal variations in cerebral blood flow. Resting heart rate and blood pressure at six time-points and blood indicators (20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids, prostaglandin E2, noradrenaline and nitric oxide) related to cerebral vascular tone at two time-points (09:00 hours and 21:00 hours) were collected to analyse possible influences on diurnal variations in cerebral blood flow. From 21:00 hours to 05:00 hours, parietal cortical relative cerebral blood flow tended to increase, while frontal cortical and cerebellar relative cerebral blood flow tended to decrease. There was a time-dependent negative correlation between parietal cortical relative cerebral blood flow and resting heart rate, whereas there was a time-dependent positive correlation between cerebellar relative cerebral blood flow and resting heart rate. The change of parietal cortical relative cerebral blood flow was positively correlated with the change of nitric oxide. There was also a time-dependent positive correlation between mean arterial pressure and mean whole-brain cerebral blood flow. The findings indicated that parietal cortical relative cerebral blood flow and frontal cortical/cerebellar relative cerebral blood flow showed roughly opposite trends throughout the day. The diurnal variations in relative cerebral blood flow were regional-specific. Diurnal variation of nitric oxide and neurogenic regulation may be potential mechanisms for diurnal variation in regional relative cerebral blood flow.

Abstract WP303: Hypertension Disrupts the Relationship Between Pial Collateral Flow and Tissue Oxygenation During Ischemic Stroke

Introduction: Chronic hypertension decreases collateral blood flow through leptomeningeal anastomoses (LMAs) during ischemic stroke, which has been linked to worsened stroke outcome. Given the important relationship between LMA flow, tissue oxygenation and cortical cerebral blood flow (CBF), we characterized the interplay between CBF and tissue oxygenation during the sub-acute progression of ischemia in normotensive Wistar (n=6) and spontaneously hypertensive rats (SHR, n=5). Methods: Transient middle cerebral artery occlusion was used to induce ischemia for 2 hours. Relative change in LMA flow, normalized to initial drop after occlusion, was measured via surface laser Doppler; tissue oxygenation and change in parenchymal CBF were measured using a combined laser Doppler-oxygen sensor placed in the expected cortical peri-infarct region. Recording was done at 400Hz, and data analyzed in 20 second blocks over the first hour of ischemia. Data reported as mean ± SEM, statistical comparisons done via Mann-Whitney tests. Results: CBF through LMAs was significantly higher in Wistars compared to SHR at 60 min of occlusion (156±18% vs 80±4% p&lt;0.05). Pial LMA flow strongly correlated with tissue CBF (Wistar: r=0.91, SHR: r=0.75), which was also greater in Wistars at 60 min compared to SHR (80±14% vs.19±3%, p&lt;0.05). Tissue oxygenation initially dropped below 10mmHg in all animals, increasing in Wistars over the course of ischemia to 22.8±0.34 mmHg at 60 min. However, oxygenation did not recover in SHR (5.9±0.23 mmHg). The relationship between CBF and oxygenation was strongly correlated in Wistar rats with both LMA (r=0.88) and tissue CBF (r=0.88). However, in SHR, oxygenation had an inverse relationship with CBF (LMA: r= - 0.56, tissue CBF r= - 0.37). Conclusion: Under normotensive conditions the relationship between CBF and oxygenation had a strong, linear relationship. However, this relationship was disrupted by chronic hypertension, with LMA and tissue CBF increasing without an increase in tissue oxygenation. This uncoupling was potentially due to cerebrovascular dysfunction and metabolic dysregulation due to chronic hypertension. These findings could be an important consideration for the development of stroke therapeutics in hypertensive patients.

Abstract 16785: Hypertension Induces Metabolite Content Alterations in Hypoperfused Mouse Brain Cortex

Introduction and aims: Hypertension is one of the main risk factors for dementias. To understand the link between vasculature and neuronal dysfunction in hypertension-induced cognitive impairment we leverage MRI, a translational imaging tool that let us concomitantly analyze cerebral structure, function and metabolism. Methods: Transverse aortic constriction (TAC) was performed in C57Bl/6J mice to induce cerebral hypertension. The brain was characterized by structural MRI, cerebral blood flow (CBF) was analyzed by perfusion MRI and cortical cerebral metabolism was characterized by point-resolved spectroscopy performed on a small-animal dedicated 7T MRI. Finally, we characterized the microvascular structure in regions impacted by hypertension by immunofluorescence. Results: TAC mice shown hemodynamic alterations in cortical CBF compared to sham mice (A). Macroscopic volumetric analyses of the cortex shown no significant alterations, however hypoperfused cortical regions shown local cortical thickening, suggesting a local swelling due to inflammatory processes (B). The histological microvascular analysis evidenced capillary Blood-Brain Barrier loss of integrity (C). Finally, this cortical region shown alterations in glucose and glutamine metabolite concentration measured by MR spectroscopy (D). Conclusions: Leveraging MRI we have concomitantly characterized the cortical structure, function and metabolism in TAC-hypertensive mice. These alterations in cerebral blood flow and metabolism of glucose/glutamine are biomarkers of ongoing cerebral injury and are potential targets of further investigation to shed light on the interplay between vascular and neuronal injury in hypertension.

Impaired dynamic cerebral autoregulation measured in the middle cerebral artery in patients with vertebrobasilar ischemia is associated with autonomic failure.

ObjectivesTo assess whether vertebrobasilar artery ischemia (VBI) affects cortical cerebral blood flow (CBF) regulation. Material and Methods107 consecutive patients (mean age 65 ± 15 years; women 21) with VBI underwent structured stroke care with assessment of dynamic cerebral autoregulation (dCA) in both middle cerebral arteries (MCAs) by transfer function analysis using spontaneous oscillations of blood pressure (BP) and CBF velocity that yields by extraction of phase and gain information in the very low (0.02-0.07 Hz), low (0.07-0.15 Hz) and high frequency (0.15-0.5 Hz) ranges. Additionally, power spectrum analysis of BP and heart rate variability (HRV) was performed. The control group consists of 29 age- and sex-matched healthy persons. ResultsCompared to controls, phase in the VBI patients was significantly reduced and gain increased in the very low frequencies (VLF), in the low (LF), phase was significantly reduced only ipsilaterally. In the high frequencies (HF), phase reduction was only marginally significant. BP power spectral density (PSD) was much higher in the patients than in the controls across all frequencies. In the PSD of heart rate variability the controls but not the patients exhibited a strong peak around 0.11Hz, while the patients, but not the controls, exhibit a strong peak around 0.36 Hz. In regression analysis, patient's phase and gain results were not related to age, sex, arterial hypertension, diabetes mellitus, renal dysfunction, heart failure as indicated by left ventricular ejection fraction, stroke subtype, presence or absence of cerebral small vessel disease. ConclusionPatients with VBI exhibit bilateral cortical autoregulation impairment in association with an autonomic nervous system disbalance. ClinicalTrials.gov IdentifierNCT04611672

48 Elevated Postconcussive Symptoms are Associated with Increased Anterior Cerebral Blood Flow and Not Cortical Thickness in Veterans with a History of Remote mTBI

Objective:Veterans with a history of mild traumatic brain injury (mTBI) often endorse enduring postconcussive symptoms (PCS) including cognitive and neuropsychiatric complaints. However, although several studies have shown associations between these complaints and brain structure and cerebrovascular function, few studies have examined relationships between structural and functional brain alterations and PCS in the context of remote mTBI. We therefore examined whether PCS were associated with cortical thickness and cerebral blood flow (CBF) in a well-characterized sample of Veterans with a history of mTBI.Participants and Methods:116 Veterans underwent structural neuroimaging and a clinical interview to obtain detailed TBI history and injury-related information. Participants also completed the following self-report measures: the Neurobehavioral Symptom Inventory (NSI) for ratings of cognitive, emotional, somatic-sensory, and vestibular symptoms, and the Posttraumatic Stress Disorder (PTSD) Checklist for PTSD symptom severity. Regional brain thickness was indexed using FreeSurfer-derived cortical parcellations of frontal and temporal regions of interest (ROIs) including the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), medial temporal lobe (MTL), and lateral temporal lobe (LTL). A subset of Veterans (n=50) also underwent multi-phase pseudo-continuous arterial spin labeling (MPPCASL) to obtain resting CBF. T1-weighted structural and MPPCASL scans were co-registered and CBF estimates were extracted from the 7 bilateral parcellations of ROIs. To assess the relationship between NSI total and subscale scores and ROI thickness and CBF, multiple regression analyses were conducted adjusting for age, sex, and PTSD symptom severity. False Discovery Rate was used to correct for multiple comparisons.Results:NSI total and subscale scores were not associated with cortical thickness of any ROI. However, higher NSI scores were associated with increased ROI CBF of the SFG (q=.014) and MFG CBF (q=.014). With respect to symptom subscales, higher affective subscale scores were associated with increased SFG (q=.001), MFG (q=.001), IFG (q=.039), ACC (q=.026), and LTL CBF (q=.026); higher cognitive subscale scores were associated with increased SFG (q=.014) and MFG CBF (q=.032); and higher vestibular subscale scores were associated with increased ACC CBF (q=.021). NSI somatic-sensory subscale scores were not associated with ROI CBF.Conclusions:Results demonstrate that in TBI-susceptible anterior ROIs, alterations in CBF but not cortical thickness are associated with postconcussive symptomatology in Veterans with a history of mTBI. Specifically, postconcussive total symptoms as well as affective, cognitive, and vestibular subscale symptoms were strongly linked primarily to CBF of frontal regions. Remarkably, these results indicate that enduring symptoms in generally younger samples of Veterans with head injury histories may be closely tied to cerebrovascular function rather than brain structure changes. These findings may provide a neurological basis for negative clinical outcomes (e.g., enduring PCS and poor quality of life) that is frequently reported by many individuals following mTBI. Future work is needed to examine unique effects of blast exposure as well as associations with repeated injury on brain-behavior relationships.

Circular RNA PTP4A2 regulates microglial polarization through STAT3 to promote neuroinflammation in ischemic stroke.

Microglial polarization plays a critical role in neuroinflammation and may be a potential therapeutic target for ischemic stroke. This study was to explore the role and underlying molecular mechanism of Circular RNA PTP4A2 (circPTP4A2) in microglial polarization after ischemic stroke. C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO), while primary mouse microglia and BV2 microglial cells experienced oxygen glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions. CircPTP4A2 shRNA lentivirus and Colivelin were used to knock down circPTP4A2 and upregulate signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. Microglial polarization was assessed using immunofluorescence staining and Western blot. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were applied to detect the binding between circPTP4A2 and STAT3. The levels of circPTP4A2 were significantly increased in plasma and peri-infarct cortex in tMCAO mice. CircPTP4A2 knockdown reduced infarct volume, increased cortical cerebral blood flow (CBF), and attenuated neurological deficits. It also decreased pro-inflammatory factors levels in peri-infarct cortex and plasma, and increased anti-inflammatory factors concentrations 24 h post-stroke. In addition, circPTP4A2 knockdown suppressed M1 microglial polarization and promoted M2 microglial polarization in both tMCAO mice and OGD/R-induced BV2 microglial cells. Moreover, circPTP4A2 knockdown inhibited the phosphorylation of STAT3 induced by oxygen-glucose deprivation. In contrast, increased phosphorylation of STAT3 partly counteracted the effects of circPTP4A2 knockdown. RNA pull-down and RIP assays further certified the binding between circPTP4A2 and STAT3. These results revealed regulatory mechanisms of circPTP4A2 that stimulated neuroinflammation by driving STAT3-dependent microglial polarization in ischemic brain injury. CircPTP4A2 knockdown reduced cerebral ischemic injury and promoted microglial M2 polarization, which could be a novel therapeutic target for ischemic stroke.

Establishment of A Mouse Model of Stellate Ganglion Block and Subsequent Biphasic Effects on Bilateral Cerebral Cortical Blood Flow

Background and objectives: Stellate ganglion block (SGB) has significant therapeutic efficacy in various clinical practices and further exploration of SGB is needed. The mouse model of SGB had not been reported and the effect on cerebral cortical blood flow (CCBF) was controversial. We aimed to establish an stellate ganglion block (SGB) mouse model and explore how SGB influences CCBF.&#x0D; Methods: Male C57BL/6 mice were randomly divided into five groups (n = 6): groups L (left SGB) and R (right SGB) received an injection of 0.25% ropivacaine hydrochloride (0.08 mL) on the respective stellate ganglion; similarly, groups SL (left saline control) and SR (right saline control) received an injection of normal saline (0.08 mL) instead. Group C received no intervention. CCBF was assessed before SGB (T0) and 10 (T1), 30 (T2), 60 (T3), 90 (T4), and 120 min (T5) after SGB using laser speckle contrast imaging system.&#x0D; Results: The SGB mouse model was successfully established in groups L and R. Compared with baseline, CCBF on the blocked side decreased at T1, increased at T2–T5, and peaked at T3 in groups L and R (all, P &lt; 0.01). Compared with groups C and SL, the CCBF on the left side decreased at T1 and increased at T2–T5 in group L (all, P &lt; 0.05). A similar trend was noted in groups C and SR relative to group R. The CCBF on the unblocked side decreased at T1, increased at T2–T5, and peaked at T3 in groups L and R (all, P &lt; 0.01).&#x0D; Conclusions: The SGB mouse model was established successfully. Unilateral SGB can affect bilateral cerebral cortical blood flow, which shows a transitory decrease followed by a significant increase for at least 2 h.

Evaluating the state of non-invasive imaging biomarkers for traumatic brain injury.

Non-invasive imaging biomarkers are useful for prognostication in patients with traumatic brain injury (TBI) at high risk for morbidity with invasive procedures. The authors present findings from a scoping review discussing the pertinent biomarkers. Embase, Ovid-MEDLINE, and Scopus were queried for original research on imaging biomarkers for prognostication of TBI in adult patients. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. Data was synthesized and confidence evaluated with the linked evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Our search yielded 3104 unique citations, 44 of which were included in this review. Study populations varied in TBI severity, as defined by Glasgow Coma Scale (GCS), including: mild (n=9), mild and moderate (n=3), moderate and severe (n=7), severe (n=6), and all GCS scores (n=17). Diverse imaging modalities were used for prognostication, predominantly computed tomography (CT) only (n=11), magnetic resonance imaging (MRI) only (n=9), and diffusion tensor imaging (DTI) (N=9). The biomarkers included diffusion coefficient mapping, metabolic characteristics, optic nerve sheath diameter, T1-weighted signal changes, cortical cerebral blood flow, axial versus extra-axial lesions, T2-weighted gradient versus spin echo, translocator protein levels, and trauma imaging of brainstem areas. The majority (93%) of studies identified that the imaging biomarker of interest had a statistically significant prognostic value; however, these are based on a very low to low level of quality of evidence. No study directly compared the effects on specific TBI treatments on the temporal course of imaging biomarkers. The current literature is insufficient to make a strong recommendation about a preferred imaging biomarker for TBI, especially considering GRADE criteria revealing low quality of evidence. Rigorous prospective research of imaging biomarkers of TBI is warranted to improve the understanding of TBI severity.

Effect of first epinephrine administration time on cerebral perfusion pressure and cortical cerebral blood flow in a porcine cardiac arrest model

ObjectiveThe optimal time for epinephrine administration and its effects on cerebral blood flow (CBF) and microcirculation remain controversial. This study aimed to assess the effect of the first administration of epinephrine on cerebral perfusion pressure (CePP) and cortical CBF in porcine cardiac arrest model. MethodsAfter 4 min of untreated ventricular fibrillation, eight of 24 swine were randomly assigned to the early, intermediate, and late groups. In each group, epinephrine was administered intravenously at 5, 10, and 15 min after cardiac arrest induction. CePP was calculated as the difference between the mean arterial pressure and intracranial pressure. Cortical CBF was measured using a laser Doppler flow probe. The outcomes were CePP and cortical CBF measured continuously during cardiopulmonary resuscitation (CPR). Mean CePP and cortical CBF were compared using analysis of variance and a linear mixed model. ResultsThe mean CePP was significantly different between the groups at 6–11 min after cardiac arrest induction. The mean CePP in the early group was significantly higher than that in the intermediate group at 8–10 min and that in the late group at 6–9 min and 10–11 min. The mean cortical CBF was significantly different between the groups at 9–11 min. The mean cortical CBF was significantly higher in the early group than in the intermediate and late group at 9–10 min. ConclusionEarly administration of epinephrine was associated with improved CePP and cortical CBF compared to intermediate or late administration during the early period of CPR.

12‐weeks of caloric restriction diet improves cortical cerebral blood flow in healthy middle‐age adults

AbstractBackgroundCaloric restriction (CR) improves neuronal stress resistance in animals and improves cognitive performance in older adults (1‐3). Neuroinflammation is an increasingly recognized mechanism relevant to Alzheimer disease (AD). We investigated the effect of a 12‐week CR diet on imaging markers of dementia and neuroinflammation in midlife individuals with multiple sclerosis (MS), a prototype neuroinflammatory disease.MethodsIn a single‐blind randomized controlled trial, 10 participants with MS (8 women and 2 men, age: 45.5±10.67 and education: 16.4±2.5 years) were recruited from the Washington University John L. Trotter MS Center and randomly assigned to participate in either a 12‐week CR or control group on their regular diet. Participants fasted 2 days a week and during those days eating no more than 500 calories. Participants underwent MRI scanning at the time of recruitment and at the end of the 12‐week program. Volumetric analyses were conducted through FreeSurfer 7.1.1 (4), relative regional cerebral blood flow (rCBF) was obtained through ASL‐MRICloud (5), and hindered and restricted diffusion fractions (HF and RF) were calculated through the diffusion basis spectrum imaging (DBSI), representing tissue edema and inflammatory cell infiltration respectivelyResultsSix participants were obese, two were overweight and two had normal weight with an average BMI of 30.3±5.48 kg/m2 across participants. Following 12‐weeks of CR, participants showed an increase in normalized hippocampal volume (p:0.02) compared to those on regular diet. CR also resulted in improved cortical thickness in the bilateral medial orbitofrontal cortices compared to the control group (p:0.014). An average increase in relative perfusion (rCBF) in the bilateral inferior temporal gyri (p:0.02, &amp; p:0.004) and bilateral fusiform gyri (p:0.008 &amp; p:0.002) was observed in participants undergoing CR compared to those on a regular diet at the end of 12‐weeks (Figure 1 and 2). Being on a CR diet was associated with reduced HF and RF in the bilateral inferior longitudinal fasciculi (p:0.04 &amp; p:0.002) indicating reduced edema and cellularity (6).ConclusionCR is associated with alterations in brain’s structure and function in terms of improved volumetric measurements, regional perfusion and reduced tissue inflammation, and hence implicated as a neuroprotective intervention in midlife persons.

White-Matter Lesions and Cortical Cerebral Blood Flow Evaluation by 3D Arterial Spin-Labeled Perfusion MRI in Asymptomatic Divers: Correlation with Patent Foramen Ovale Ocurrence.

Cerebral white-matter lesions (cWML) can be caused by dilation of Virchow-Robin spaces or may correspond to true lacunar ischemic lesions. The aim of our study was to evaluate in asymptomatic divers the relationship between the presence of patent foramen ovale (PFO) and cWML, as well as their possible effects on cortical cerebral blood flow (CBF) by magnetic resonance (MRI) through the arterial spin labeling (ASL) sequence. Transthoracic echocardiography was performed for the identification of PFO, and cerebral magnetic resonance including the 3D-ASL sequence for CBF quantification. Thirty-eight divers, with a mean age 45.8 ± 8.6 years, were included. Nineteen healthy volunteers, mean age 41 ± 15.2 years, served as the control group. A total of 28.9% of divers had completed more than 1000 dives. It was found that 26.3% of divers presented with PFO in the echocardiographic study. cWML was evidenced in 10.5% of diver MRI studies. There was no statistically significant relationship between the presence of PFO and cWML (p = 0.95). We observed a lower blood flow in all brain areas assessed by the 3D-ASL sequence in the group of divers, compared with the control group. We did not find statistical differences in CBF as a function of the presence or absence of PFO, number of dives, or cWML evidence.

Regional cerebral blood flow and brain atrophy in mild cognitive impairment and Alzheimer's disease.

A decline in the regional cerebral blood flow (CBF) is proposed to be one of the initial changes in the Alzheimer's disease process. To date, there are limited data on the correlation between CBF decline and gray matter atrophy in mild cognitive impairment (MCI) and AD patients. to investigate the association between CBF with the gray matter structural parameters such as cortical volume, surface area, and thickness in AD, MCI, and healthy controls (HC). Data from three groups of participants including 39 HC, 82 MCI, and 28 AD subjects were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI). One-way ANOVA and linear regression were used to compare data and find a correlation between structural parameters such as cortical volume, surface area, and thickness and CBF which measured by arterial spin labeling (ASL)-MRI. Our findings revealed a widespread significant correlation between the CBF and structural parameters in temporal, frontal, parietal, occipital, precentral gyrus, pericalcarine cortex, entorhinal cortex, supramarginal gyrus, fusiform, precuneus, and pallidum. CBF decline may be a useful biomarker for MCI and AD and accurately reflect the structural changes related to AD. According to the present results, CBF decline, as measured by ASL-MRI, is correlated with lower measures of structural parameters in AD responsible regions. It means that CBF decline may reflect AD-associated atrophy across disease progression and is also used as an early biomarker for AD and MCI diagnosis.