Journal of Cerebral Blood Flow and Metabolism最新文献

The optimal neuroimaging modalities for differentiating intracranial atherosclerotic stenosis-related large vessel occlusion (ICAS-LVO) from embolism related LVO remain uncertain. This study aimed to address this question by directly comparing collateral circulation using either baseline CT perfusion (CTP) or multiphase CT angiogram (mCTA) to define collaterals. We retrospectively analyzed consecutive patients with acute large vessel occlusion from October 2021 to December 2023. All patients underwent CTP before endovascular therapy, and mCTA was reconstructed from CTP data. In-situ ICAS-LVO was confirmed by a neuro-interventional radiologist. Favorable collateral circulation was defined as a collateral index <0.4 on CTP or a collateral score ≥3 on mCTA. Of 377 patients, 72 (19%) had ICAS-LVO. Patients with only a collateral score ≥3 did not show significantly higher odds of ICAS-LVO (P = 0.681). In contrast, those with a collateral index <0.4 but not favorable mCTA collateral had higher odds of ICAS-LVO (OR2.69, 95%CI [1.07-7.01], P = 0.037). Subgroup analysis showed that a collateral grading scale ≥3 may not predict ICAS-LVO within 6 hours, whereas CTP's predictive performance remained consistently strong in both early and late windows. CTP defined favorable collaterals of collateral index <0.4 demonstrate greater predictive value for ICAS-LVO compared to mCTA, especially within an early time window.

Cerebral aneurysm rupture has a poor prognosis, and growing aneurysms are prone to rupture. We therefore conducted a prospective observational study to clarify hemodynamics inducing aneurysm growth, which are poorly understood. Computational fluid dynamics analysis was performed using the patient-specific arterial geometry and flow velocities. Hemodynamic metrics were compared by multivariate analysis between aneurysms enlarged ≥1 mm and stable aneurysms. We enrolled 481 patients. For aneurysms <4 mm, the time-averaged wall shear stress (WSS) was significantly higher in growing aneurysms for the whole aneurysm, neck, body and parent artery, and transverse WSS was significantly higher on the neck and parent artery. In aneurysms ≥4 mm, the normalized transverse WSS was significantly higher in growing aneurysms for the whole aneurysm and dome. Aneurysms <4 mm were likely to show whole-aneurysm growth, while aneurysms ≥4 mm were enlarged at the dome. There may exist two hemodynamic mechanisms for aneurysm growth depending on size. Aneurysms <4 mm may grow near the neck with high magnitudes and multi-directional WSS disturbances, while aneurysms ≥4 mm may grow on the dome with enhanced multi-directional WSS disturbance. These results may be useful in considering indications for surgical treatment. They may help resolve two conflicting hemodynamic rupture theories.

The studies explored cerebral small vessel disease (cSVD), emphasizing the need for precise classification to improve prevention and intervention strategies. Kang et al. introduced an intra-cisterna-magna bevacizumab injection (ICM-BI) model in mice, which induced tight junction loss, microbleeds, and amyloid deposits. However, bevacizumab's low affinity for murine vascular endothelial growth factor raises questions about its mechanism of action, suggesting potential off-target effects. While most cSVD models mimic arteriolosclerosis (type 1) or genetic variants (types 2 and 3), the ICM-BI model represents a novel approach to studying immune-mediated cSVD (type 4). The complexity and variability of cSVD remain significant research challenges.

This study aimed to investigate the impact of controlling serum homocysteine on improving surgical outcomes in patients with moyamoya disease (MMD) and hyperhomocysteinemia. In this prospective observational cohort study, 477 patients with MMD post-encephaloduroarteriosynangiosis are divided into the HHcy-MMD post-control group (n = 193), HHcy-MMD uncontrolled group (n = 91), and MMD group (n = 193), with the HHcy-MMD post-control group further subdivided into good (homocysteine 0-10 μmol/L, n = 121) and general (homocysteine 10-15 μmol/L, n = 72) control groups. The differences in imaging and long-term clinical prognosis among the three groups were compared. No significant differences were noted in the Matsushima grade after encephaloduroarteriosynangiosis between the MMD group and HHcy-MMD post-control group (P > 0.05); however, there was a significant difference between the HHcy-MMD post-control group and HHcy-MMD uncontrolled group (P < 0.001). A significant difference was noted between the good and general control groups in the Matsushima grade (P = 0.025) and long-term follow-up clinical outcomes (P = 0.035). The area under the curve of homocysteine levels for predicting adverse clinical outcomes was 85.48% (95% confidence interval: 80.31-90.65%). Effective control of serum Hcy level after EDAS surgery in Moyamoya disease patients with HHcy may lead to better prognosis.Clinical Trial Registration: This study was registered at ClinicalTrials.gov (NCT03613701).

The Alzheimer's disease (AD) continuum is characterized by amyloid and tau protein deposition, which is partly attributable to the dysfunction of the brain clearance system. However, the specific phase in the AD continuum wherein aberrant clearance is present remains unclear. This study aimed to assess noninvasive magnetic resonance imaging (MRI) indices related to brain clearance functions, such as choroid plexus volume (CPV), lateral ventricular volume (LVV), and the index of diffusivity along the perivascular space (ALPS index), across the Alzheimer's disease (AD) spectrum. The CPV, LVV, and ALPS index in amyloid beta (Aβ)-negative healthy controls (HCs) and Aβ-positive HCs as well as in patients with Aβ-negative subjective cognitive decline (SCD), with Aβ-positive SCD, with mild cognitive impairment, and with AD were evaluated. The CPV and LVV were higher, whereas the ALPS index was lower in the patients with more severe disease. The ALPS index was significantly lower in Aβ-positive HCs than in Aβ-negative HCs. In SCD patients and those in the AD continuum, the MRI-based clearance markers were correlated with P-tau and T-tau protein levels and cognitive scores. In summary, brain clearance markers on MRI are associated with tau deposition, neurodegeneration and cognitive dysfunction.

Cerebrovascular reactivity (CVR) and cerebral pulsatility (CP) are important indicators of cerebrovascular health, which are associated with physical activity (PA). While sex differences influence the impact of PA on cerebrovascular health, sex-specific effects of PA intensity and dose on CP and CVR remains unknown. This study aimed to evaluate the sex-specific effects of self-reported PA dose and intensity on CVR and CP. The Human Connectome Project - Aging dataset was used, including 626 participants (350 females, 276 males) aged 36-85. The effect of menopausal status was also assessed. Resting state fMRI data was used to estimate both CVR and CP. Weekly self-reported PA was quantified as metabolic equivalent of task. Females presented a unique non-linear relationship between relative CVR and total PA in the cerebral cortex. Females and menopausal subgroups revealed negative linear relationships with total and walking PA in occipital and cingulate regions. Males exhibited negative linear relationships between total and vigorous PA and CVR in parietal and cingulate regions. Postmenopausal females showed greater reductions across more regions in CP than other groups. Overall, males and females appear to benefit from different amounts and intensities of PA, with menopause status influencing the effect of PA on cerebrovascular health.

Chimeric antigen receptor T (CAR-T) cells have made brilliant achievements in the treatment of many kinds of malignant tumors, and six kinds of CAR-T products have been approved by the Food and Drug Administration (FDA), bringing new hope for the treatment of diseases. However, the complications associated with CAR-T cell therapy should not be ignored. Neurological complications often jeopardize patients' lives, including immune effector cell-associated neurotoxicity syndrome, cerebrovascular accidents, movement and neurocognitive treatment-emergent adverse events. The current knowledge of the mechanism and treatment of these complications is still insufficient, which is a direction that needs to be solved in the future.

Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, and the specific role of IL-1α in ischemic stroke remain largely unknown. Here we show that IL-1α and IL-1β have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1α expression (4 h) and delayed IL-1β expression in infiltrated neutrophils and a small microglial subset (24-72 h). We examined for the first time the specific role of microglial-derived IL-1α in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1α deletion did not influence acute outcome after ischemic stroke. However, microglial IL-1α knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1α on post-stroke neurorepair and recovery, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop effective therapies.

Perfusion through leptomeningeal collateral vessels is a likely pivotal factor in the outcome of ischemic stroke patients. Acupuncture has been reported to restore cerebral blood flow (CBF) after acute ischemic stroke, but the underlying mechanisms are poorly understood. This study aimed to examine whether electroacupuncture (EA) could improve CBF following an acute ischemic injury by regulating leptomeningeal collaterals. The clinical outcomes suggest that EA resulted in an increase in the average CBF within the whole brain and gray matter of healthy subjects compared to pre-intervention. The experiments conducted on animals revealed that EA was able to improve neurological function, reduce infarct volume, and salvage tissue damage in the peri-infarct areas of permanent middle cerebral artery occlusion rats. Additionally, EA was found to increase cerebral perfusion and the diameter of developed leptomeningeal anastomoses, accompanied by activation of cholinergic neurons of the nucleus basalis of Meynert (NBM). However, these effects of EA were reversed by chemogenetic inhibition of cholinergic neurons in the NBM or by intraperitoneal injection of acetylcholine receptors antagonist atropine. These findings suggest that EA improved CBF after acute ischemic stroke, partially via activating cholinergic projections from the NBM to the cortex, thereby promoting leptomeningeal collateral circulation. ClinicalTrials.gov identifier: NCT03444896.

Neurofibrillary tangles (NFTs), composed of aggregated tau protein, in the brain is a neuropathological hallmark and feature of Alzheimer's disease (AD) and other tauopathies. One promising approach to prevent tau aggregates is to inhibit O-GlcNAcase (OGA), an enzyme that regulates tau O-GlcNAcylation. [¹¹C]BIO-1819578 has emerged as a promising candidate to determine target occupancy of such OGA inhibitor drugs. The aim of this study was to further evaluate the pharmacokinetic properties of [¹¹C]BIO-1819578 in non-human primates (NHPs) and to estimate its effective dose. Kinetic compartment analyses of [¹¹C]BIO-1819578 binding to OGA in the brain were performed on positron emission tomography (PET) measurements conducted in three cynomolgus NHPs. Whole-body PET measurements were carried out in two NHPs to estimate the effective radiation dose. Both the 1-tissue-compartment (1TCM) and 2-tissue-compartment model (2TCM) could describe the regional time activity curves of [¹¹C]BIO-1819578. The 2TCM was the statistically preferred model. The effective radiation dose was estimated to be 0.0033 mSv/MBq. The results showed that [¹¹C]BIO-1819578 has suitable characteristics for reliable quantification of OGA using full kinetic modelling. The effective dose was on par with other ¹¹C radioligands and is unlikely to pose an issue for human use.