Cerebral Blood Flow Research Articles

Do Different Amounts of Exogenous Surfactant Differently Influence Cerebrovascular Instability in a Consecutive Group of Preterm Babies? Preliminary Results from a Single-Center Experience.

Thirty years ago, the first attempt by Saliba and colleagues was made to reduce the negative effects (hypercarbia) of exogenous surfactant (ES) by slowing its administration. Sixteen years later, we observed the first less invasive surfactant administration (LISA) attempt by Kribs and colleagues. Many studies, since that time, have tried to minimize the invasiveness of ES and subsequent cerebral blood flow perturbations through studies using near-infrared spectroscopy (NIRS). We sought to address this medical challenge by identifying a less problematic modality of ES administration by delivering multiple aliquots of ES instead of a single one, as typically performed. The aim of this study was to test the hypothesis that a different way of administering ES using more aliquots could be a safe alternative that should be assessed in further studies. Patients between 26 + 0 and 35 + 6 weeks of gestational age (GA) requiring ES administration were enrolled (April 2023-February 2024). Differently fractioned doses were delivered according to an arbitrary standard dosage (0.3 mL per aliquot in babies < 29 weeks; 0.6 mL in babies ≥ 29 weeks), while NIRS and transcutaneous CO2 (tCO2) monitoring were always performed. ES's effectiveness was assessed based on the reduction in the Oxygen Saturation Index (OSI) after administration. Persistent desaturation, bradycardia, and airway obstruction were defined as adverse effects and used to evaluate safety during ES administration, as well as variability in NIRS-rSO2 values and tCO2. Twenty-four patients were enrolled with a median GA of 29 weeks (IQR 4.5) and BW of 1223 ± 560 g. In addition, 50% of the cohort received fewer than three aliquots, whereas the other 50% received more than three. Monitoring was started before the procedure and continued 30' after the last ES aliquot administration. The variability in NIRS-SpO2 values was significantly higher in the group (p = 0.007) with a lower number of aliquots administered. Similarly, increased NIRS-rSO2 values (p = 0.003) and increased tCO2 levels (p = 0.005) were observed in infants who underwent an ES split after the administration of a low number of aliquots. Our data obtained from the group with > 3 fractionated doses of ES seem to justify the preparation of a more robust study, as the combination of reduced NIRS variability and reduced tCO2 maximum levels is consistent with more stable cerebral blood flow during the challenging time of ES administration.

Perfusion-weighted MRI patterns in neuropsychiatric systemic lupus erythematosus: a systematic review and meta-analysis.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a complex manifestation of Systemic Lupus Erythematosus (SLE) characterized by a wide range of neurological and psychiatric symptoms. This study aims to elucidate the patterns of Perfusion-Weighted MRI (PWI) in NPSLE patients compared to SLE patients without neuropsychiatric manifestations (non-NPSLE) and healthy controls (HCs). A systematic search was conducted in PubMed/Medline, Embase, Web of Science, and Scopus for studies utilizing PWI in NPSLE patients published through April 14, 2024. Cerebral blood flow (CBF) data from NPSLE, non-NPSLE patients, and HCs were extracted for meta-analysis, using standardized mean difference (SMD) as an estimate measure. For studies lacking sufficient data for inclusion, CBF, cerebral blood volume (CBV), and mean transit time (MTT) were reviewed qualitatively. Our review included eight observational studies employing PWI techniques, including dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL). The meta-analysis of NPSLE compared to non-NPSLE incorporated four studies, encompassing 104 NPSLE patients and 90 non-NPSLE patients. The results revealed an SMD of -1.42 (95% CI: -2.85-0.00, I2: 94%) for CBF in NPSLE compared to non-NPSLE. PWI reveals informative patterns of cerebral perfusion, showing a significant reduction in mean CBF in NPSLE patients compared to non-NPSLE patients. Our qualitative synthesis highlights these changes, particularly in the frontal and temporal lobes. However, the existing data exhibits considerable heterogeneity and limitations.

Effects of Prostaglandin E1 and Balloon Atrial Septostomy on Cerebral Blood Flow and Oxygenation in Newborns Diagnosed with Transposition of the Great Arteries.

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders followed by alterations in synaptogenesis, gyrification, sulcation, and the microstructure. Brain injuries can occur both pre-operatively and postoperatively, especially white matter injuries, neuronal loss, and stroke. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess the resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure, and 24 h after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1 + BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. In addition, 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group, but lower than in controls at 24 h of life, while cFTOE remained elevated. The RI increased 24 h after delivery (0.718 vs. 0.769; p = 0.000002) due to decreased EDV (10.71 vs. 8.74; p < 0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 h of life in the PGE1 + BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusions: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period, as reflected by increasing SpO2 and crSO2.

Disturbed Dynamic Brain Activity and Neurovascular Coupling in End-Stage Renal Disease Assessed With MRI.

Pathophysiological mechanisms underlying cognitive impairment in end-stage renal disease (ESRD) remain unclear, with limited studies on the temporal variability of neural activity and its coupling with regional perfusion. To assess neural activity and neurovascular coupling (NVC) in ESRD patients, evaluate the classification performance of these abnormalities, and explore their relationships with cognitive function. Prospective. Exactly 33 ESRD patients and 35 age, sex, and education matched healthy controls (HCs). The 3.0T/3D pseudo-continuous arterial spin labeling, resting-state functional MRI, and 3D-T1 weighted structural imaging. Dynamic (dfALFF) and static (sfALFF) fractional amplitude of low-frequency fluctuations and cerebral blood flow (CBF) were assessed. CBF-fALFF correlation coefficients and CBF/fALFF ratio were determined for ESRD patients and HCs. Their ability to distinguish ESRD patients from HCs was evaluated, alongside assessment of cerebral small vessel disease (CSVD) MRI features. All participants underwent blood biochemical and neuropsychological tests to evaluate cognitive decline. Chi-squared test, two-sample t-test, Mann-Whitney U tests, covariance analysis, partial correlation analysis, family-wise error, false discovery rate, Bonferroni correction, area under the receiver operating characteristic curve (AUC) and multivariate pattern analysis. P < 0.05 denoted statistical significance. ESRD patients exhibited higher dfALFF in triangular part of left inferior frontal gyrus (IFGtriang) and left middle temporal gyrus, lower CBF/dfALFF ratio in multiple brain regions, and decreased CBF/sfALFF ratio in bilateral superior temporal gyrus (STG). Compared with CBF/sfALFF ratio, dfALFF, and sfALFF, CBF/dfALFF ratio (AUC = 0.916) achieved the most powerful classification performance in distinguishing ESRD patients from HCs. In ESRD patients, decreased CBF/fALFF ratio correlated with more severe renal impairment, increased CSVD burden, and cognitive decline (0.4 < |r| < 0.6). ESRD patients exhibited abnormal dynamic brain activity and impaired NVC, with dynamic features demonstrating superior discriminative capacity and CBF/dfALFF ratio showing powerful classification performance. 1 TECHNICAL EFFICACY: Stage 1.

Impairments of neurovascular coupling after stroke lower glymphatic system function and lead to depressive symptom: A longitudinal cohort study

BackgroundRespective changes in neurovascular coupling (NVC) and glymphatic function have been reported in post-stroke depression (PSD). Recent studies have found a link between NVC and waste clearance by the glymphatic system, which has not been illustrated in PSD. MethodWe prospectively recruited ninety-six stroke patients and forty-four healthy controls (HC), with fifty-nine patients undergoing a second MRI scan. NVC metrics were investigated by exploring Pearson correlation coefficients and ratios between cerebral blood flow (CBF) and BOLD-derived quantitative maps (ALFF, fALFF, REHO maps). Diffusion tensor imaging along the perivascular (DTI-ALPS) index was used to reflect glymphatic function. We first analyzed the altered NVC metrics in stroke patients relative to the HC group. Then, we explored the relationship between NVC metrics, ALPS index and depressive symptoms at baseline and during the follow-up period through correlation and mediation analyses. ResultsStroke patients exhibited significantly lower global CBF-fALFF coupling and ALPS index. At the regional level, abnormal NVC alterations in brain regions involved in cognition, emotion, and sensorimotor function in PSD. Baseline analyses showed that ALPS index exhibited positive associations with both global and local NVC and abnormal regional NVC may contribute to generation of PSD by reducing glymphatic function (β = −0.075, p < 0.05, CI = [−0.169 to −0.012]). Longitudinal analyses similarly showed that ALPS index changes were positively associated with changes in NVC and mediated improvements in depressive symptoms. ConclusionOur findings suggest that NVC abnormalities leading to impaired glymphatic system function may be a potential neurobiological mechanism of PSD.

Comparison of Perfusion Imaging Definitions of the No-Reflow Phenomenon after Thrombectomy-What Is the Best Perfusion Imaging Definition?

We performed an external validation of 4 existing published definitions of no-reflow in thrombectomy patients with extended Thrombolysis in Cerebral Infarction scale 2c to 3 (eTICI2c-3) angiographic reperfusion who underwent 24-hour perfusion imaging from 2 international randomized controlled trials (EXTEND-IA TNK part-1 and 2) and a multicenter prospective observational study. Receiver-operating-characteristic and Bayesian-information-criterion (BIC) analyses were performed with the outcome variable being dependent-or-dead at 90-days (modified Rankin Score [mRS] ≥3). Of 131 patients analyzed, the prevalence of no-reflow significantly varied between definitions (0.8-22.1%; p < 0.001). There was poor agreement between definitions (kappa 5/6 comparisons <0.212). Among patients with no-reflow according to at least 1 definition, there were significant differences between definitions in the intralesional interside differences in cerebral blood flow (CBF) (p = 0.006), cerebral blood volume (CBV) (p < 0.001), and mean-transit-time (MTT) (p = 0.005). No-reflow defined by 3 definitions was associated with mRS ≥3 at 90 days. The definition of >15% CBV or CBF asymmetry was the only definition that improved model fit on BIC analysis (ΔBIC = -8.105) and demonstrated an association between no-reflow and clinical outcome among patients with eTICI3 reperfusion. Existing imaging definitions of no-reflow varied significantly in prevalence and post-treatment perfusion imaging profile, potentially explaining the variable prevalence of no-reflow reported in literature. The definition of >15% CBV or CBF asymmetry best discriminated for functional outcome at 90 days, including patients with eTICI3 reperfusion. ANN NEUROL 2024.

Super-Resolving and Denoising 4D flow MRI of Neurofluids Using Physics-Guided Neural Networks.

To obtain high-resolution velocity fields of cerebrospinal fluid (CSF) and cerebral blood flow by applying a physics-guided neural network (div-mDCSRN-Flow) to 4D flow MRI. The div-mDCSRN-Flow network was developed to improve spatial resolution and denoise 4D flow MRI. The network was trained with patches of paired high-resolution and low-resolution synthetic 4D flow MRI data derived from computational fluid dynamic simulations of CSF flow within the cerebral ventricles of five healthy cases and five Alzheimer's disease cases. The loss function combined mean squared error with a binary cross-entropy term for segmentation and a divergence-based regularization term for the conservation of mass. Performance was assessed using synthetic 4D flow MRI in one healthy and one Alzheimer' disease cases, an in vitro study of healthy cerebral ventricles, and in vivo 4D flow imaging of CSF as well as flow in arterial and venous blood vessels. Comparison was performed to trilinear interpolation, divergence-free radial basis functions, divergence-free wavelets, 4DFlowNet, and our network without divergence constraints. The proposed network div-mDCSRN-Flow outperformed other methods in reconstructing high-resolution velocity fields from synthetic 4D flow MRI in healthy and AD cases. The div-mDCSRN-Flow network reduced error by 22.5% relative to linear interpolation for in vitro core voxels and by 49.5% in edge voxels. The results demonstrate generalizability of our 4D flow MRI super-resolution and denoising approach due to network training using flow patches and physics-based constraints. The mDCSRN-Flow network can facilitate MRI studies involving CSF flow measurements in cerebral ventricles and association of MRI-based flow metrics with cerebrovascular health.

Neurovascular coupling and CO2 interrogate distinct vascular regulations

Neurovascular coupling (NVC), which mediates rapid increases in cerebral blood flow in response to neuronal activation, is commonly used to map brain activation or dysfunction. Here we tested the reemerging hypothesis that CO2 generated by neuronal metabolism contributes to NVC. We combined functional ultrasound and two-photon imaging in the mouse barrel cortex to specifically examine the onsets of local changes in vessel diameter, blood flow dynamics, vascular/perivascular/intracellular pH, and intracellular calcium signals along the vascular arbor in response to a short and strong CO2 challenge (10 s, 20%) and whisker stimulation. We report that the brief hypercapnia reversibly acidifies all cells of the arteriole wall and the periarteriolar space 3–4 s prior to the arteriole dilation. During this prolonged lag period, NVC triggered by whisker stimulation is not affected by the acidification of the entire neurovascular unit. As it also persists under condition of continuous inflow of CO2, we conclude that CO2 is not involved in NVC.

Perfusion Abnormalities on 24-Hour Perfusion Imaging in Patients With Complete Endovascular Reperfusion.

Perfusion abnormalities in the infarct and salvaged penumbra have been proposed as a potential reason for poor clinical outcome (modified Rankin Scale score >2) despite complete angiographic reperfusion (Thrombolysis in Cerebral Infarction [TICI3]). In this study, we aimed to identify different microvascular perfusion patterns and their association with clinical outcomes among TICI3 patients. University Hospital Bern's stroke registry of all patients between February 2015 and December 2021. Macrovascular reperfusion was graded using the TICI scale. Microvascular reperfusion status was evaluated within the infarct area on cerebral blood volume and cerebral blood flow perfusion maps obtained 24-hour postintervention. Primary outcome was functional independence (90-day modified Rankin Scale score 0-2) evaluated with the logistic regression analysis adjusted for age, sex, and 24-hour infarct volume from follow-up imaging. Based on microvascular perfusion findings, the entire cohort (N=248) was stratified into one of the 4 clusters: (1) normoperfusion (no perfusion abnormalities; n=143/248); (2) hyperperfusion (hyperperfusion on both cerebral blood volume and cerebral blood flow; n=54/248); (3) hypoperfusion (hypoperfusion on both cerebral blood volume and cerebral blood flow; n=14/248); and (4) mixed (discrepant findings, eg, cerebral blood volume hypoperfusion and cerebral blood flow hyperperfusion; n=37/248). Compared with the normoperfusion cluster, patients in the hypoperfusion cluster were less likely to achieve functional independence (adjusted odds ratio, 0.3 [95% CI, 0.1-0.9]), while patients in the hyperperfusion cluster tended to have better outcomes (adjusted odds ratio, 3.3 [95% CI, 1.3-8.8]). In around half of TICI3 patients, perfusion abnormalities on the microvascular level can be observed. Microvascular hypoperfusion, despite complete macrovascular reperfusion, is rare but may explain the poor clinical course among some TICI3 patients, while a detrimental effect of hyperperfusion after reperfusion could not be confirmed.

Abstract 21: The Detrimental Effects of a Comorbidity of Increased Blood Pressure Variability and High Salt Diet on Cardiovascular and Neurovascular Outcomes

Recent studies have identified increased blood pressure variability (BPV) as a novel risk factor for cognitive decline, independently from absolute BP values. However, the underlying mechanisms are poorly defined. In addition, whether a high salt diet (HSD) contributes to BPV and exacerbates cognitive decline is not known. We tested the hypothesis that vascular damage resulting from blood pressure fluctuations in BPV disrupts critical mechanisms regulating cerebral blood flow (CBF), impairing perfusion and leading to neurovascular dysfunction and cognitive decline. We established a murine BPV model and evaluated the impact of BPV on systemic BP (baroreceptor reflex) and CBF regulation (myogenic and functional hyperemia (FH) responses). Mice were implanted with a cranial window for in-vivo two-photon (2P) imaging. A programmable pump infused 6-8 pulses/day of angiotensin II ((Ang II 18 µg/day) (BPV) or saline (Control) for 25 days, and cardiovascular variables were measured via DSI telemetry. Ang II pulse infusions evoked transient BP increases (Δ43±4 mmHg, MAP; P&lt;0.01,n=8); however, did not induce hypertension in the BPV group. BPV mice displayed increased BPV index (P=0.04,n=12) and cognitive decline (novel object recognition test (P=0.01,n=10)). Telemetry data showed a decrease in bradycardic responses following chronic BPV (P=0.03, n=8). Data from 2P studies showed enhanced myogenic response in parenchymal arterioles of BPV vs Controls (P&lt;0.01,n=9-15 runs) when BP transitions from low to high BP. We observed a blunted FH in BPV vs Control during low BP (P&lt;0.01,n=6-7). During high BP, FH was pronounced in Controls (P&lt;0.01,n=6-7); however, pressure-induced vascular responses were abolished in BPV mice (P&lt;0.01,n=6-7). In separate groups of mice, the Control and BPV protocol was repeated with all mice receiving a high-salt diet (HS; 4% NaCl chow+1% NaCl drinking water: Control+HS or BPV+HS). There were no changes in 24-hr MAP in Control+HS (P&gt;0.85, n=5). Whereas BPV+HS mice developed sustained hypertension (increased 24-hr MAP; P&lt;0.01, n=4). These data demonstrate that BPV alters mechanisms regulating CBF and BP, contributing to cognitive decline and that HSD may exacerbate the detrimental effects of BPV on BP regulating mechanisms. Ongoing studies are examining the comorbid effects of BPV+HS on the cerebrovasculature and direct CBF changes in BPV and BPV+HS mice.

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.

Predicting white-matter hyperintensity progression and cognitive decline in patients with cerebral small-vessel disease: a magnetic resonance-based habitat analysis.

White-matter hyperintensity (WMH) is the key magnetic resonance imaging (MRI) marker of cerebral small-vessel disease (CSVD). This study aimed to investigate whether habitat analysis based on physiologic MRI parameters can predict the progression of WMH and cognitive decline in CSVD. Diffusion- and perfusion-weighted imaging data were obtained from 69 patients with CSVD at baseline and at 1-year of follow-up. The white-matter region was classified into constant WMH, growing WMH, shrinking WMH, and normal-appearing white matter (NAWM) according to the T2-fluid-attenuated inversion recovery (FLAIR) sequences images at the baseline and follow-up. We employed k-means clustering on a voxel-wise basis to delineate WMH habitats, integrating multiple diffusion metrics and cerebral blood flow (CBF) values derived from perfusion data. The WMH at the baseline and the predicted WMH from the habitat analysis were used as regions of avoidance (ROAs). The decreased rate of global efficiency for the whole brain structural connectivity was calculated after removal of the ROA. The association between the decreased rate of global efficiency and Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) scores was evaluated using Pearson correlation coefficients. We found that the physiologic MRI habitats with lower fractional anisotropy and CBF values and higher mean diffusivity, axial diffusivity, and radial diffusivity values overlapped considerably with the new WMH (growing WMH of baseline) after a 1-year follow-up; the accuracy of distinguishing growing WMH from NAWM was 88.9%±12.7% at baseline. Similar results were also found for the prediction of shrinking WMH. Moreover, after the removal of the predicted WMH, a decreased rate of global efficiency had a significantly negative correlation with the MoCA and MMSE scores at follow-up. This study revealed that a habitat analysis combining perfusion with diffusion parameters could predict the progression of WMH and related cognitive decline in patients with CSVD.

Glymphatic System Impairment in the Advanced Stage of Moyamoya Disease.

Assessing the glymphatic system activity using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) may be helpful to understand the pathophysiology of moyamoya disease (MMD). 63 adult patients with MMD and 20 healthy controls (HCs) were included for T1-weighted images, T2-FLAIR, pseudocontinuous arterial spin labeling, and DTI. 60 patients had digital subtraction angiography more than 6 months after combined revascularization. The Suzuki stage, postoperative Matsushima grade, periventricular anastomoses (PA), enlarged perivascular spaces (EPVS), deep and subcortical white matter hyperintensities (DSWMH), DTI-ALPS, cerebral blood flow (CBF), and cognitive scales of MMD patients were assessed. MMD patients were divided into early and advanced stage based on the Suzuki stage. We detected lower DTI-ALPS in patients with advanced stage relative to HCs (p = 0.046) and patients with early stage (p = 0.004), hemorrhagic MMD compared with ischemic MMD (p = 0.048), and PA Grade 2 compared with Grade 0 (p = 0.010). DTI-ALPS was correlated with the EPVS in basal ganglia (r = -0.686, p < 0.001), Suzuki stage (r = -0.465, p < 0.001), DSWMH (r = -0.423, p = 0.001), and global CBF (r = 0.300, p = 0.017) and cognitive scores (r = 0.343, p = 0.018). The DTI-ALPS of patients with good postoperative collateral formation was higher compared to those with poor postoperative collateral formation (p = 0.038). In conclusion, the glymphatic system was impaired in advanced MMD patients and may affected cognitive function and postoperative neoangiogenesis.

Exploring the translational impact of type 1 diabetes on cerebral neurovascular function through ECoG-LSCI.

Type 1 diabetes mellitus (T1DM) can result in complications such as retinopathy, nephropathy, and peripheral neuropathy, which can lead to brain dysfunction. In this study, we investigated the effects of T1DM on cerebral neurovascular function in mice. Streptozotocin (STZ) is known to induce T1DM in animals; thus, we used an STZ-induced diabetes model to evaluate the effects of hyperglycemia on brain morphology and neurovascular tissue. Neurovascular coupling is the connection between neuronal activity and cerebral blood flow that maintains brain function. The ECoG-LSCI technique combines electrocorticography (ECoG) and laser speckle contrast imaging (LSCI) to detect cortical spreading depression (CSD) as a marker of neurovascular coupling and measure corresponding neurovascular function. Our results suggested that in the STZ group, hyperglycemia affected excitatory neurotransmission and metabolism, leading to reductions in intercellular signaling, somatosensory evoked potential (SSEP) amplitudes, and CSD transmission rates. Western blot data further revealed that brain-derived neurotrophic factor (BDNF) and neuronal nuclear antigen levels were reduced in the STZ group. Abnormalities in glucose metabolism in the brain and increased phosphorylation of AKT and GSK3 are hypothesized to be responsible for these decreases. Overall, this study highlights the importance of glucose metabolism in normal brain physiology and demonstrates that hyperglycemia disrupts neurovascular coupling and affects cerebral neurovascular function and that the degree of CSD is positively correlated with the extent of brain tissue damage. Further research is essential to gain a complete understanding of the related mechanisms and the implications of these findings.

Abstract P193: Adoptive transfer of placental CD4+ T Cells from preeclamptic patients with a history of COVID-19 causes hypertension and cognitive dysfunction postpartum in a pregnant rat model of preeclampsia

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with activated CD4+ T cells, impaired cognitive function, and changes in cerebral blood flow (CBF) autoregulation. Previously, PE women have been shown to develop neurovascular and cardiovascular disorders earlier in life than those that had uneventful pregnancy. COVID-19 (CV) during pregnancy is associated with an increase incidence of the PE phenotype and is also associated with chronic neurovascular and cardiovascular consequences. Previously, we showed adoptive transfer of placental CD4+ T cells from PE women into athymic nude pregnant rats causes a PE phenotype, however we don’t know the role of CD4+ T cells to cause long-term neurovascular or cardiovascular consequences in PE in the presence or absence of a history (Hx) of COVID-19 during pregnancy. Therefore, we hypothesize that CD4+ T cells from PE patients with and without a Hx of CV causes hypertension and neurovascular dysfunction compared to CD4+ T cells from normotensive patients. One million placental CD4+ T cells from Normotensive (NT), CV Hx NT, and PE patients with or without a CV Hx were isolated and injected interperitoneally (i.p.) into pregnant nude athymic rats on gestational day (GD) 12. Dams were allowed to deliver and aged 12-weeks after delivery. At 12-weeks postpartum, blood pressure (MAP) was measured; CBF autoregulation was measured by laser Doppler flowmetry. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function 12-weeks postpartum. A two-way ANOVA was used for statistical analysis. At 12-weeks postpartum, MAP increased in CV Hx PE (153±6, n=7, p&lt;0.05) and PE (150±5 mmHg, n=5, p&lt;0.05) compared to CV Hx NT (121±6, n=6) and NT (116±6 mmHg, n=6), respectively. Behavioral analysis showed CV Hx PE and PE exhibited impaired memory and learning (P&lt;0.05) compared to either NT group. Our findings indicate that rat recipients of CD4+ T cells from PE patients in the presence or absence of CV Hx have HTN and cognitive dysfunction in the postpartum period compared to recipients of control CD4 + T cells. These data indicate the importance of CD4+ T cells in long-term consequences of PE and COVID infection during pregnancy.

Nervonic acid alleviates stroke and its associated poststroke depression behaviors

Nervonic acid (NA) is an important long-chain monounsaturated fatty acid found in mammalian nervous tissue. It has recently garnered research attention due to its therapeutic potential in treating psychiatric and neurodegenerative disorders. In this study, we investigated the efficacy of NA in treating ischemia/reperfusion and poststroke events in a rat model. Specifically, there was significant reduction in the infarct area, cell death, and neuronal swelling after NA treatment, and the improvement in cerebral blood flow was also observed on day five after middle cerebral artery occlusion. Moreover, NA treatment led to the upregulation of brain-derived neurotrophic factors and myelin basic protein genes. NA displayed improved effects on depressive-like behavior of rats by three validated assays—the sucrose preference test, open-field test, and forced swim test. Regarding the mechanism of action, direct supplementation of NA in the brain was observed. We also observed the indirect effects of NA on the gut microbiota. Notably, the NA group gradually restored the bacterial diversity and the EGb group exhibited no impact based on observed-out analysis. We found an increase in the abundance of Blautia and Sutterella, which participated in phenylalanine metabolism. The metabolomics of plasma and brain samples revealed a decrease in the levels of phenylalanine-based amino acids, which alleviated the inhibitory effects on glutamine metabolism and promoted the recovery and signaling transmission of neurons after stroke. Altogether, our findings suggest that NA can be a viable treatment option for alleviating stroke and its associated poststroke depressive-like behaviors.

Neuroimaging analysis reveals distinct cerebral perfusion responses to fasting-postprandial metabolic switching in Alzheimer's disease patients.

Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.

Pseudo-continuous and territorial arterial spin labeling MRI for assessment of cerebral perfusion in moyamoya disease after revascularization: A comparative study with digital subtraction angiography

PurposeTo evaluate if pseudo-continuous arterial spin labeling (pcASL) and territorial ASL (tASL) can assess cerebral perfusion post-revascularization in Moyamoya disease and compare with digital subtraction angiography (DSA) outcomes. Materials and methodsPatients diagnosed with Moyamoya disease who underwent pcASL using two post-labeling delays (short ASL, 1,525 ms; delayed ASL, 2,525 ms), tASL, and DSA 3 months after surgery at a single institution were retrospectively evaluated. Manual delineation on pcASL cerebral blood flow (CBF) maps covered middle cerebral artery (MCA) territory on both sides, and cerebellum. Normalized CBF (nCBF) was calculated. Revascularization in the MCA territory was evaluated with external carotid angiography and tASL, graded on a three-point scale. Intermodality agreement was analyzed with weighted κ statistics. Correlation between pcASL-derived nCBF and tASL-measured revascularization, and revascularization grade from direct angiography, was determined. Diagnostic performance of pcASL and tASL was evaluated using DSA as a reference via receiver operating characteristic (ROC) curve analysis. ResultsA total of 32 hemispheres from 31 patients were assessed. On the operated side, sASL and dASL had nCBF values of 1.00 ± 0.30 and 1.31 ± 0.31, respectively. Revascularization area grading showed substantial intermodality agreement (weighted κ = 0.68; 95 % CI: 0.49, 0.87). DSA revascularization moderately correlated with sASL and dASL nCBF values (r = 0.56 and 0.47) and strongly correlated with tASL revascularization area (r = 0.73). ROC analysis revealed that sASL and dASL nCBF values reflected revascularization (area under the curve (AUC) = 0.86 and 0.77) and tASL revascularization area (AUC = 0.91). Combined pcASL and tASL had an AUC of 0.93, comparable to tASL alone, improving diagnostic performance. The diagnostic accuracy of nCBF for sASL was 87.5 %, superior to 75 % for dASL. The diagnostic accuracy of tASL external carotid artery revascularization area was 87.5 %, with sensitivity and specificity of 88 % and 85.7 %, respectively. ConclusionThe combination of pcASL and tASL outperformed pcASL alone in assessing cerebral perfusion post-Moyamoya disease revascularization.

Abstract P132: Sex Differences in Cerebrovascular Dysfunction in the APP/PS1 TgF344-AD Rat Model of Alzheimer's Disease

Alzheimer's Disease (AD) is the primary cause of dementia and is characterized by extracellular beta-amyloid plaques and intracellular hyperphosphorylated tau-containing neurofibrillary tangles in the brain. Emerging evidence suggests that cerebrovascular dysfunction is associated with AD. Although two-thirds of AD patients are female, sex differences in transgenic AD models have been largely ignored. The present study investigated sex differences in cerebrovascular dysfunction and potential mechanisms in AD using a TgF344-AD rat model. The APP/PS1 TgF344-AD (AD) rats serve as a preferred model to study AD since they recapitulate the complete repertoire of AD-like pathologies in humans. We previously longitudinally characterized cerebral hemodynamics in male TgF344 AD rats at 3, 4, 6, and 14 months, and reported that 4-month-old AD males displayed early signs of impaired cerebral blood flow (CBF) autoregulation and reduced functional hyperemia, two months earlier than memory loss, which was co-occurred with the appearance of plaques. These deficits progressed with advancing age. The present study used 13-14 months of female TgF344-AD (AD) and F344 (WT) rats. We found that AD females also displayed impaired learning and memory function in the eight-arm swim and open field tests as seen in males. Amyloid plaques were prominent in the hippocampus and cortex of female AD brains at a similar level in males, while no plaques were observed in WT brains. Functional hyperemic responses to whisker stimulation were markedly impaired in female AD rats. Further, we found evidence of astrocyte activation and microgliosis in female AD brains using immunohistochemistry and western blots. The astrocytes and microglial activation formed clusters around amyloid plaques. The direct contact between astrocytic endfeet and penetrating arterioles was markedly reduced in AD animals. Moreover, the blood-brain barrier (BBB) was disrupted in AD animals as the tight junction marker ZO1 was significantly reduced in AD brains. These results demonstrate cerebrovascular dysfunction contributes to loss of cognitive function in both male and female APP/PS1 TgF344-AD rats and is associated with impaired functional hyperemia, loss of astrocytic endfeet on penetrating arterioles, BBB breakdown, neuroinflammation related to amyloid plaques. They also indicate that the female TgF344-AD rat is appropriate for studying age-related influences of sex hormones on AD.

Sex Disparities in Mortality After Endovascular Therapy in Large Core Infarcts

Background In recent large core endovascular therapy (EVT) trials of large vessel occlusion acute ischemic stroke (AIS), treatment was associated with reduced rates of mortality. Because post‐AIS mortality can be influenced by societal and biological factors that differ between women and men, we investigate sex‐based differences in mortality outcomes following EVT in large core AIS. Methods From our prospectively collected multicenter registry across 4 comprehensive stroke centers in the Greater Houston area, we identified patients from 2017 to 2022 with large vessel occlusion AIS and large infarct core. Large infarct core was defined by computed tomography perfusion exceeding 70 mL (by regional cerebral blood flow measurements using automated postprocessing) or computed tomography Alberta Stroke Program Early CT [Computed Tomography] Score&lt;6. The primary outcome of this study was the likelihood of mortality at 90 days, determined through multivariable logistic regression adjusted for EVT, sex, and EVT/sex interaction term. Secondary outcomes included 90‐day disability outcomes and intracerebral hemorrhage. Results Among 190 patients who met inclusion criteria, 50% were female and 45.3% received EVT. Demographic differences between the sexes were largely balanced apart from the older age of presentation for women compared with men (75 versus 67, women versus men; P &lt;0.01). In univariable analysis, women who did not receive EVT had greater mortality (27.4% difference; P &lt;0.001) compared with men, with comparable rates in EVT‐treated cohorts. In multivariable analysis, non‐EVT management was strongly associated with mortality in women compared with men at discharge (odds ratio [OR] 5.81, 95% CI [1.96–17.23]) and 90‐days (OR 6.77, 95% CI [2.09–21.94]). In the secondary analysis, which additionally adjusted the model for age and National Institutes of Health Stroke Scale score, these findings were unchanged. The sex/EVT interaction term showed significant interaction for mortality both at discharge and 90 days ( P &lt;0.01). Conclusion EVT in large core AIS populations may disparately reduce mortality in women compared to men.