Search Results (802)

Background/Objectives: The use of quantitative neuroimaging to establish objective biomarkers in neurodegenerative diseases (NDD) has attracted increasing interest over the last decade. Advanced magnetic resonance imaging (MRI) such as arterial spin labeling (ASL) and diffusion tensor imaging (DTI), as well as [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET), could provide clinically meaningful biomarkers and may support differential diagnosis. The aim of this investigator-initiated, single-center, retrospective comparative study was to implement a framework for multimodal neuroimaging to evaluate cases with rare NDD, using a methodological approach that integrates metabolic, perfusion, and microstructural parameters from simultaneous FDG-PET/MRI, and to investigate its potential to facilitate diagnosis. Methods: Three patients with pathological motor signs (1f/2m; 63, 73, and 52 years) and 19 control subjects with subjective cognitive deficits (SCDs) underwent combined FDG-PET/MRI with pseudo-continuous ASL and DTI. Standardized uptake values (SUVs), relative cerebral blood flow (rCBF), and fractional anisotropy (FA) were calculated to identify pattern alterations in individual patients based on parameterization mapping. The final diagnosis was corticobasal degeneration (CBD, n = 1) or primary lateral sclerosis (PLS, n = 2). Results: At the individual patient level, disease-specific changes in defined brain regions could be demonstrated and quantified compared to control subjects. All three patients showed significantly decreased FA, primarily along parts of the course of the corticospinal tract (CST). In the patient with CBD, asymmetric SUVR and rCBF decreases were observed, mostly overlapping with motor regions. In the two patients with PLS, SUVR revealed mostly unspecific findings (hypothetically due to a slow progression rate or due to potentially early disease stages), while ASL indicated decreased rCBF primarily overlapping within the motor cortex. Changes at the gray matter level were primarily located adjacent to changes in white matter, as indicated by the multimodal analysis approach using simultaneously acquired FDG-PET/MRI data. Conclusions: According to this proof-of-concept study, multimodal neuroimaging by the combination of quantitative MRI and FDG-PET has the potential to guide differential diagnosis in rare NDDs, especially if clinical diagnosis is not straightforward to achieve. Since particularly early diagnosis remains essential for patient counseling, effective treatment, and clinical management, the present framework appears helpful to be developed further until it aligns and integrates with clinical routine. Full article

Moyamoya disease is a progressive steno-occlusive cerebrovascular disorder in which cerebral perfusion may become highly dependent on systemic arterial pressure, arterial carbon dioxide tension, and collateral flow. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization procedure that promotes neovascularization over weeks to months but does not immediately augment cerebral blood flow intraoperatively. Anesthetic management therefore requires preservation of cerebral oxygen delivery during a period of persistent physiologic vulnerability. This narrative review presents a practical perioperative framework for EDAS anesthesia, emphasizing maintenance of mean arterial pressure near baseline or modestly above baseline, avoidance of hypotension and hypovolemia, normoxia, normothermia, and careful regulation of carbon dioxide. Hyperventilation should be avoided because hypocapnia can reduce cerebral blood flow through vasoconstriction, while excessive hypercapnia may contribute to regional maldistribution or steal physiology. Raw electroencephalography may provide cortical ischemia surveillance where available, whereas somatosensory evoked potentials, motor evoked potentials, near-infrared spectroscopy, and transcranial Doppler should be considered adjunctive and institution-dependent. A structured algorithm that integrates hemodynamics, ventilation, oxygen delivery, anesthetic depth, neuromonitoring, and surgical communication may support the timely recognition and correction of intraoperative hypoperfusion. Full article

Introduction: Decompressive craniectomy (DC) is often required to stabilize the intracranial pressure (ICP) in patients with traumatic brain injury (TBI). Both sinking flap syndrome (SFS) and hydrocephalus are known complications of DC. The pathophysiology of each is unknown. Case Report: We report on a patient who underwent DC for TBI who suffered both SFS and low-pressure hydrocephalus. We measured the changes in volumes of each hemisphere and the ventricles with CT and the cerebral blood flow (CBF) and aqueduct flow with phase-contrast MRI during different stages of the disease process. Discussion: The SFS in this patient was associated with a reduction in volume of both supratentorial cavities. There was a significant reduction in CBF bilaterally, which increased by an average of 26% following cranioplasty. During the low-pressure hydrocephalus phase of the patient’s illness, there was reversed CSF flow directed toward the ventricles. Once the ventricles returned to normal size, this reversed flow was lost. Conclusions: Lumped parameter modelling of the patients’ CSF and vascular systems suggested a new hypothesis, i.e., that the reduction in blood flow was due to reversible constriction of the arterioles secondary to a reset of the autoregulation rather than compression of the venous structures. We suggest there is an increase in CSF absorption efficiency despite the known CSF-absorption mechanisms being unlikely to function at such a low ICP. A hypothesis is put forward that CSF absorption occurs via the brain capillary bed in these diseases. Full article

Stress alters hemodynamic regulation through intricate brain–body pathways, translating psychological phenomena into systemic cardiovascular changes. This review explores these complex neurobiological mechanisms, focusing on how the autonomic nervous system and hypothalamic–pituitary–adrenal axis orchestrate pathological fluctuations in heart rate, vascular resistance, and blood pressure. The neurophysiological data link limbic system hyperactivation to endothelial dysfunction and altered cerebral blood flow. Furthermore, we investigate the bidirectional nature of this relationship wherein stress-induced hemodynamic instability can exacerbate psychiatric conditions. Bridging affective neuroscience with cardiovascular physiology, this integrative framework underscores the critical need for multidisciplinary clinical approaches in managing stress-related psychosomatic and cardiovascular pathologies. Full article

Background/Objectives: Diagnosing hemangioblastomas using magnetic resonance imaging (MRI) is challenging, especially when the tumors appear as solid posterior fossa masses. This study aimed to evaluate the diagnostic performance of perfusion MRI and identify the most useful quantitative features for differentiating hemangioblastomas from other posterior fossa tumors. Methods: Forty-five posterior fossa tumors were analyzed, including 18 hemangioblastomas (HB group) and 27 non-hemangioblastoma tumors (NHB group; 8 metastatic brain tumors, 6 pilocytic astrocytomas, 5 malignant lymphomas, 4 glioblastomas, 2 medulloblastomas, and 2 other tumors). All patients underwent 3.0-T MRI. Arterial spin labeling (ASL) was used to calculate the relative tumor blood flow normalized to the contralateral gray matter. Dynamic susceptibility contrast (DSC) imaging was used to obtain regional cerebral blood flow, regional and corrected cerebral blood volume (CBV), and permeability index (K2) values. Regions of interest (ROIs) were placed within the contrast-enhancing areas. Results: The relative ASL values and corrected CBV were significantly higher in hemangioblastomas than in other tumors (p < 0.001). Relative ASL showed the highest diagnostic performance (sensitivity, 100%; specificity, 93.3%). Conclusions: Non-contrast ASL showed strong diagnostic performance for identifying posterior fossa hemangioblastomas and may serve as a practical alternative to contrast-enhanced DSC, although ROI placement can be challenging in very small mural nodules. Full article

Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and investigated their anti-ischemic activities both in vitro and in vivo, aiming to identify candidates with high safety and improved efficacy compared with Pts. The ADMET method was used to predict the drug-likeness of a series of Pts derivatives, and in vitro MTT cell viability analysis was conducted on neuroblastoma cells (SH-SY5Y) and brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reperfusion (OGD/R) injury. On the basis of the cytotoxicity results, four derivatives (NO. 1, NO. 3, NO. 5, and NO. 7) were selected for subsequent in vitro and in vivo biological activities evaluation. These compounds exhibited significantly higher TI values (18.29–30.61) in OGD/R-injured hBMECs compared with Pts (7.63) and effectively suppressed apoptosis, promoted cell migration, and enhanced tube formation capacity. In vivo, NO. 3 (5 mg/kg, ip., 7 d) demonstrated superior efficacy compared to Pts in improving cerebral blood flow, reducing infarction volume, enhancing neurological function, and modulating serum biomarker levels in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, whereas NO. 1 and NO. 7 showed comparable efficacy to Pts. The acute intraperitoneal toxicity of NO. 3 was conducted and showed that the LD₅₀ of NO. 3 was estimated to be more than 300 mg/kg. In this study, the rational design and comprehensive evaluation of Pts derivatives were reported. Compound NO. 3 demonstrated superior pharmacological efficacy to Pts both in vitro and in vivo, and it may be a promising therapeutic candidate for ischemic stroke intervention. Full article

Cerebrovascular and neurodegenerative diseases are often linked to dysregulated cerebral blood flow, which results in oxidative stress and alterations in energy metabolism. Targeting the underlying initiators and exacerbating factors could offer protective benefits. Among the proposed therapeutic agents, the steroid hormone progesterone (P4) has shown considerable potential. This study evaluates the protective effects of P4 (1.7 mg/kg, administered subcutaneously once daily for a week) in a rat model of chronic cerebral hypoperfusion (CCH), provoked by the permanent bilateral ligation of the common carotid arteries. Redox and metabolic imbalances, specifically lipid and adenine nucleotide metabolism, were examined in serum and striatal crude synaptosomal fractions. Additionally, sensorimotor functions were assessed using non-invasive neurological tests. Biochemical analyses showed that P4 in CCH conditions contributed to the normalization of redox and metabolic homeostasis in both the serum and striatum. In the serum, this was accompanied by increased adenine nucleotide turnover, likely favoring protective adenosine signaling. In parallel, P4 alleviated the striatal oxidative burden while augmenting antioxidant response and promoting nucleotide catabolism. Our findings demonstrate that P4-mediated protection is accomplished through coordinated biochemical serum–striatum responses, linking systemic and synaptic metabolic regulation with improved sensorimotor function and recovery from CCH-induced deficits. Full article

Ischemic stroke, a major cause of global disability, is characterized by the blockage of an artery leading to reduced cerebral blood flow and subsequent brain injury. Automatic segmentation of ischemic stroke lesions in Computed Tomography Perfusion (CTP) maps is critical for accurate diagnosis, treatment planning, and outcome assessment. However, the accuracy of traditional methods remains limited, with Dice Similarity Coefficient (DSC) values around 68%. To address this challenge, we propose a deep learning-based model inspired by biological systems and brain mechanisms, which emulates natural information processing to enhance ischemic stroke lesion segmentation. The proposed network architecture consists of five graph convolutional layers that automatically extract and classify features from CTP images. We evaluated the model using the ISLES 2018 database, achieving a DSC of 75.41% and a Jaccard Index of 74.52%, representing significant improvements over previous methods. Notably, the proposed approach performs robustly in noisy environments, maintaining accuracy above 60% even at SNR = −4. These results demonstrate the potential of biomimetic-inspired networks for automatic ischemic stroke segmentation. Full article

Alzheimer’s disease (AD) is a neurodegenerative disease impacting over 6 million Americans, with cases projected to increase to over 14 million by 2060. The AD pathology leads to difficulty completing everyday tasks or conversations, and ultimately, progresses to disrupt the most basic bodily functions and require full-time caretaking. While disease-modifying therapy remains elusive, reducing the incidence of AD is crucial to mitigate the projected increase in cases. Exercise has emerged as an effective strategy to promote brain health in late adulthood and to protect against the onset of AD. Exercise opposes several disease processes, including cognitive dysfunction, amyloid beta aggregation, tau phosphorylation, and deficits in hippocampal volume, mitochondrial function, cerebral blood flow, and neurogenesis, through various pathways, including the systemic release of exerkines. The exerkine irisin is an important mediator of the beneficial relationship between exercise and the brain. Previous work administering irisin therapeutically to healthy and preclinical AD mice has demonstrated irisin use to replicate multiple exercise-induced effects in the brain and protect against AD-induced deficits. Although irisin is suggested as a promising strategy for promoting brain health in late adulthood, our understanding of irisin signaling and its protective effects against AD remains incomplete. This review will investigate irisin as an important, physiologically relevant promoter of brain health in aging and AD. Full article

Background and purpose: Short-term external counterpulsation (ECP) noninvasively augments cerebral blood flow by elevating blood pressure in ischemic stroke. The current retrospective case–control study examined the effect of long-term ECP treatment on blood pressure and beat-to-beat blood pressure variability (BPV) in patients with recent ischemic stroke. Method: The ECP group included data from 20 recent ischemic stroke patients who received five daily 1 h sessions each week for seven weeks, for a total of 35 sessions of ECP treatment from our ECP registry. An equivalent comparative control group without ECP treatment was composed from the same pool of patients and matched with cases by sex and age. Beat-to-beat heart rate and blood pressure were monitored before and after the long-term intervention. Power spectral analysis calculated the beat-to-beat BPV oscillations at very low frequency (VLF; <0.04 Hz), low frequency (LF; 0.04–0.15 Hz), high frequency (HF; 0.15–0.40 Hz), and the total power spectral density (TP; <0.40 Hz) and LF/HF ratio. Result: There was a significant reduction in systolic blood pressure (SBP) after the intervention compared with that before intervention in both groups (p < 0.05), but only the ECP group displayed a statistically significant reduction in diastolic blood pressure (DBP) (p = 0.023). The changes in SBP and DBP (delta SBP and delta DBP) from pre-intervention to completion showed no significant differences between the two groups (all p > 0.05). The ECP group exhibited a more pronounced and significant decrease in each spectral component of BPV after the intervention than at pre-intervention, with a substantial decrease in systolic BPV at TP (p = 0.048) and in the LF/HF ratios (p = 0.021 in diastolic BPV and p = 0.004 in systolic BPV, respectively) compared to the control group. Conclusions: A standard 35-session ECP treatment decreases beat-to-beat BPV but does not change SBP and DBP in patients with recent ischemic stroke. This implies that long-term ECP treatment may enhance autonomic regulation to benefit post-stroke clinical outcomes. Full article

Background/Objectives: Snow Chrysanthemum (Coreopsis tinctoria Nutt.), a traditional medicinal and edible plant rich in flavonoids (TFSC) with antihypertensive and neuroprotective activities, has unclear effects and mechanisms on vascular dementia (VaD) comorbid with hypertension, a key risk factor accelerating VaD. This study aimed to investigate TFSC’s ameliorative effects on cognitive impairment in hypertensive VaD rats and elucidate its holistic therapeutic mechanisms. Methods: Spontaneously hypertensive rats (SHRs) with unilateral common carotid artery ligation were used to establish the hypertensive VaD model. TFSC was intragastrically administered for 11 weeks. Systolic blood pressure (BP) and cerebral blood flow (CBF) were monitored; cognitive function was assessed via open field, novel object recognition and Morris water maze tests. Histopathological changes were evaluated by H&E and Nissl staining, serum oxidative stress and inflammatory markers were measured, and hippocampal transcriptome sequencing plus RT-qPCR was performed to identify key pathways and genes. Results: The chemical profile of TFSC was characterized, showing a total flavonoid content of 84.96%; 49 compounds were identified, 39 of which were flavonoids. TFSC reduced BP, improved CBF, alleviated cognitive dysfunction and neuronal damage, enhanced antioxidant capacity (increased SOD, CAT, GSH; decreased ROS), and exerted anti-inflammatory effects (reduced TNF-α, IL-1β, IL-6, Ang-II). It modulated multiple pathways, with the PI3K-Akt and MAPK pathways enriched, and validated key differentially expressed genes. Conclusions: This study provides preliminary evidence for the holistic therapeutic potential of TFSC against hypertensive VaD. With integrated vascular regulatory and neuroprotective effects, TFSC serves as a promising candidate for VaD by targeting both vascular risk factors and neuropathological damage. Full article

Background: Isolated Generalized Dystonia (IGD) severely reduces quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is effective for refractory IGD, but the factors influencing efficacy remain unclear. Methods: Twelve IGD patients treated with bilateral STN-DBS (2016–2021) were retrospectively analyzed. Clinical outcomes (BFMDRS, HAMA, HAMD, MOCA, MMSE) were evaluated at baseline and the last follow-up (12–60 months). The electrode position and volume of tissue activated (VTA) in STN subregions were analyzed using Lead-DBS V3.0. Results: STN-DBS significantly improved BFMDRS-M and BFMDRS-D scores (p < 0.001) without cognitive or mood deterioration. BFMDRS-M improvement correlated positively with the VTA of the whole STN and motor subregion (p < 0.05) but not with associative/limbic subregions. The preoperative HAMD score was negatively associated with motor improvement (p = 0.002). Conclusions: STN-DBS safely improves motor function in IGD. Efficacy depends on the VTA within the STN sensorimotor subregion. The preoperative HAMD score may predict the long-term outcome, helping guide patient selection and surgical planning. Full article

Background and Purpose: Neurological injury remains a major complication of pediatric cardiac surgery and is closely related to alterations in cerebral blood flow during extracorporeal circulation (ECC). However, the real-time assessment of cerebral perfusion under these conditions has been limited by the lack of magnetic resonance (MR)-compatible perfusion systems. The aim of this pilot feasibility study was to establish a porcine model enabling simultaneous cardiopulmonary bypass (CPB) and real-time MR-based assessment of cerebral blood flow during simulated pediatric cardiac surgery. Methods: We conducted a pilot study on 11 Duroc pigs (14.6 ± 1.4 kg BW), designed in iterative cycles. The experimental setup included an MR-conditional heart-lung machine and a surgical protocol closely mimicking pediatric cardiac surgery. After the initiation of CPB and hemodynamic stabilization, animals were cooled to target temperatures (20 °C or 28 °C) depending on the perfusion strategy. Structural and functional MRI, including phase-contrast imaging, arterial spin labeling, diffusion-weighted imaging, and MR spectroscopy, were performed during cooling and rewarming. Procedural feasibility, technical challenges, and optimization strategies were systematically documented. Results: The study successfully established a reproducible porcine model enabling MR imaging during extracorporeal circulation. Key technical challenges, including vascular access, cannulation of the ascending aorta, and blood volume management, were identified and addressed through the iterative refinement of the surgical and perfusion protocols. The use of the Seldinger technique significantly improved cannulation safety and reduced blood loss. Stable CPB conditions and target hypothermic temperatures were achieved in successfully cannulated animals. MRI acquisition during CPB was feasible, providing simultaneous structural and functional assessment of cerebral perfusion. Representative imaging data demonstrate the capability of the model to capture cerebral hemodynamics in real time. Conclusions: This pilot study establishes a novel MR-compatible porcine model for the real-time assessment of cerebral blood flow during extracorporeal circulation. The platform provides a robust foundation for future quantitative investigations of cerebral perfusion, mechanisms of brain injury, and neuroprotective strategies in pediatric cardiac surgery. Full article

Neuronal activity and cerebral blood flow are tightly coupled to support the high metabolic demands of the brain. Disruption of neurovascular coupling is a defining feature of many neurodegenerative disorders such as Alzheimer’s disease, stroke, small vessel disease, Parkinson’s disease, and aging. Progress in understanding the mechanisms underlying neurovascular coupling requires experimental approaches that can simultaneously measure neuronal activity and vascular dynamics with high spatial and temporal resolution, while also enabling targeted perturbations of the system. Here, we present a methodological framework that combines chronic electrophysiological recordings with two-photon imaging of cerebral blood flow and optogenetic manipulation of the vasculature in vivo. Using a chronically implanted flexible electrode array, we obtain measurements of the single- and multi-unit spiking activity, as well as local field potentials. Concurrently, two-photon microscopy enables high-resolution measurements of vessel diameter and blood flow within individual vascular segments. In addition, optogenetic control of vascular smooth muscle cells allows for rapid and reversible manipulation of the vessel diameter through the same cranial window while simultaneously recording the neural and vascular activity. We provide detailed protocols for surgical implantation, data acquisition, and analysis, and discuss experimental considerations and limitations. This combined platform offers a powerful tool for mechanistic studies of neurovascular coupling and its dysfunction in disease models. Full article

Cerebral ischemic stroke is caused by impaired blood flow to the brain parenchyma due to acute vessel occlusion. Although current therapies focusing on rapid restoration of blood flow achieve high rates of recanalization, outcomes remain unfavorable in a significant proportion of patients. Part of this discrepancy is due to intravascular inflammation driven by thrombo-inflammatory mechanisms that add to cerebral tissue loss. Despite being an inevitable consequence of vessel occlusion, altered shear stress remains largely overlooked as a contributor to endothelial dysfunction in stroke. To directly assess the impact of disturbed flow on the endothelial phenotype, human brain endothelial cells were cultured under controlled flow conditions using an ibidi pump system and exposed to flow alternating in both magnitude and direction. Subsequently, the expression of key endothelial proteins, including Claudin-5, PECAM-1, CD62e and endoglin, was analyzed. We show here that the sequence of shear-stress modulation, recapitulating the hemodynamic conditions of large-vessel occlusion and subsequent reperfusion in stroke, is sufficient to cause an inflammatory phenotype in human brain endothelial cells. In addition, we demonstrate that platelet activation induces the mechanosensors Piezo1 and syndecan-1, sensitizing brain endothelial cells to shear-stress alterations characteristic of ischemic stroke. Targeting shear-stress-mediated inflammatory activation of the brain endothelium may therefore offer a complementary strategy in stroke therapy, particularly in large-vessel occlusion with abrupt flow changes. Full article