Journal of Cerebral Blood Flow and Metabolism

Cell therapy and regenerative medicine have made remarkable progress in treating neurodegenerative disorders. Induced pluripotent stem cells (iPSCs) offer a promising source for cell replacement therapies, but their practical application faces challenges due to poor survival and integration after transplantation. Park et al. propose a novel therapeutic strategy involving the co-transplantation of regulatory T cells (Tregs) and iPSC-derived dopamine neurons. This combined approach enhances the survival of transplanted cells and protects against neuroinflammation-induced damage...

A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial...

The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein. Right internal jugular vein blood flow was measured using Duplex ultrasound, and tritiated NA was infused through the participants' right superficial forearm vein...

The near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx) has become popularized for non-invasive neuromonitoring of cerebrovascular function in post-cardiac arrest patients with hypoxic-ischemic brain injury (HIBI). We provide commentary on the physiologic underpinnings and assumptions of NIRS and the COx, potential confounds in the context of HIBI, and the implications for the assessment of cerebral autoregulation.

As few studies have reported the impact of lower left ventricular ejection fraction (LVEF) on the prognosis of acute ischemic stroke (AIS) patients, we aimed to explore this through a retrospective cohort study and a meta-analysis. A total of 283 AIS patients receiving intravenous thrombolysis at the Third Affiliated Hospital of Wenzhou Medical University between 2016 and 2019 were enrolled and divided into three groups based on LVEF tertiles. The logistic regression model estimated the association between LVEF and the three-month AIS prognosis...

The goal of neurocritical care is to prevent and reverse the pathologic cascades of secondary brain injury by optimizing cerebral blood flow, oxygen supply and substrate delivery. While glucose is an essential energetic substrate for the brain, we frequently observe a strong decrease in glucose delivery and/or a glucose metabolic dysregulation following acute brain injury. In parallel, during the last decades, lactate and ketone bodies have been identified as potential alternative fuels to provide energy to the brain, both under physiological conditions and in case of glucose shortage...

A mounting body of research points to cerebrovascular dysfunction as a fundamental element in the pathophysiology of Parkinson's disease (PD). In the current feasibility study, blood-oxygen-level-dependent (BOLD) MRI was used to measure cerebrovascular reactivity (CVR) in response to hypercapnia in 26 PD patients and 16 healthy controls (HC), and aimed to find a multivariate pattern specific to PD. Whole-brain maps of CVR amplitude (i.e., magnitude of response to CO2 ) and latency (i.e., time to reach maximum amplitude) were computed, which were further analyzed using scaled sub-profile model principal component analysis (SSM-PCA) with leave-one-out cross-validation...

Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via 15 O-gas positron emission tomography (PET), and all patients underwent cognitive tests...

Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 ( RNF213 ), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVECWT ) or p...

Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo)...

Metabolomic analysis of cerebrospinal fluid (CSF) is used to improve diagnostics and pathophysiological understanding of neurological diseases. Alterations in CSF metabolite levels can partly be attributed to changes in brain metabolism, but relevant transport processes influencing CSF metabolite concentrations should be considered. The entry of molecules including metabolites into the central nervous system (CNS), is tightly controlled by the blood-brain, blood-CSF, and blood-spinal cord barriers, where aquaporins and membrane-bound carrier proteins regulate influx and efflux via passive and active transport processes...

The blood-brain barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules and cells between the blood and the central nervous system. It undergoes structural and functional changes during aging, which may compromise its integrity and contribute to the pathogenesis of neurodegenerative diseases. In recent years, advances in microscopy and high-throughput bioinformatics have allowed a more in-depth investigation of the aging mechanisms of BBB. This review summarizes age-related alterations of the BBB structure and function from six perspectives: endothelial cells, astrocytes, pericytes, basement membrane, microglia and perivascular macrophages, and fibroblasts, ranging from the molecular level to the human multi-system level...

Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues...

Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging...

Vascular pathology is the second leading cause of cognitive impairment and represents a major contributing factor in mixed dementia. However, biomarkers for vascular cognitive impairment and dementia (VCID) are under-developed. Here we aimed to investigate the potential role of CO2 Cerebrovascular Reactivity (CVR) measured with phase-contrast quantitative flow MRI in cognitive impairment and dementia. Forty-five (69 ± 7 years) impaired (37 mild-cognitive-impairment and 8 mild-dementia by syndromic diagnosis) and 22 cognitively-healthy-control (HC) participants were recruited and scanned on a 3 T MRI...

A metabolic coupling between glutamate and N-acetylaspartate measured by in vivo magnetic resonance spectroscopy has been recently reported in the literature with inconsistent findings. In this study, confounders originating from Pearson's spurious correlation of ratios and spectral correlation due to overlapping magnetic resonance spectroscopy signals of glutamate and N-acetylaspartate were practically eliminated to facilitate the determination of any metabolic link between glutamate and N-acetylaspartate in the human brain using in vivo magnetic resonance spectroscopy...

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted within PubMed and reference sections of articles identified from April 2014 to November 2022...

Stimulation of the M4 muscarinic acetylcholine receptor reduces striatal hyperdopaminergia, suggesting its potential as a therapeutic target for schizophrenia. Emraclidine (CVL-231) is a novel, highly selective, positive allosteric modulator (PAM) of M4 muscarinic acetylcholine receptors i.e. acts as a modulator that increases the response of these receptors. First, we aimed to further characterize the positron emission tomography (PET) imaging and quantification performance of a recently developed M4 PAM radiotracer, [11 C]MK-6884, in non-human primates (NHPs)...

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...

Driven and spontaneous methods have been used to quantify the cerebral pressure-flow relationship via transfer function analysis (TFA). Commonly, TFA derived estimates are assessed using band averages within the very-low (0.02-0.07 Hz) and low (0.07-0.20 Hz) frequency during spontaneous oscillations but are quantified at frequencies of interest where blood pressure oscillations are driven (e.g., 0.05 and/or 0.10 Hz). Driven estimates more closely resemble the autoregulatory challenges individuals experience on a daily basis, while also eliciting higher levels of reliability...