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Many recent research projects have described typical chronic changes in the retinal vasculature for diverse neurovascular and neurodegenerative disorders such as stroke or Alzheimer's disease. Unlike cerebral vasculature, retinal blood vessels can be assessed non-invasively by retinal vessel analysis. To date, there is only a little information about potential simultaneous reactions of retinal and cerebral vessels in acute neurovascular diseases. The field of applications of retinal assessment could significantly be widened if more information about potential correlations between those two vascular beds and the feasibility of non-invasive retinal vessel analysis in acute neurovascular disease were available. Here, we present our protocol for the simultaneous assessment of retinal and cerebral vessels in an acute setting in anesthetized rats using a non-invasive retinal vessel analyzer and a superficial tissue imaging system for laser speckle contrast analysis via a closed bone window. We describe the experimental set-up in detail, outline the pitfalls of repeated retinal vessel analyses in an experimental set-up of several hours, and address issues that arise from the simultaneous use of two different assessment tools. Finally, we demonstrate the robustness and variability of the reactivity of retinal vessels to hypercapnia at baseline as well as their reproducibility over time using two anesthetic protocols common for neurovascular research. In summary, the procedures described in this protocol allow us to directly compare retinal and cerebral vascular beds and help to substantiate the role of the retina as a “window to the brain.” [ABSTRACT FROM AUTHOR]

Study Design: Retrospective single-arm study. Objective: To propose a novel technique named the gantry crane technique for treating severe thoracic spinal stenosis and myelopathy caused by thoracic ossification of the ligamentum flavum (TOLF) and investigate its clinical results. Methods: From June 2017 to January 2019, 18 patients presenting with severe spinal stenosis and myelopathy caused by TOLF were included in our study. All patients were treated with gantry crane technique, pre-operative JOA score, as well as 3 days-, 3 months-, 6 months-, 12 months-, 24 months after operation, and Hirabayashi recovery rate were reported. Pre- and post-operative image were utilized for the assessment of post-operative effect. Peri-operative complications were recorded to assess the safety of the gantry crane technique. Results: The JOA score increased from 10.56 ± 3.76 preoperatively to 12.94 ± 3.33, 13.56 ± 3.48, 13.94 ± 3.32, 14.17 ± 3.70 and 14.06 ± 3.54 in 3 days, 3 months, 6 months, 12 months and 24 months after surgery, respectively. The post-operative JOA scores were improved with statistical significance at the level of P < 0.05. The recovery rate was (39.09 ± 33.85) %, (51.35 ± 42.60) %, (55.79 ± 36.10) %, (64.98 ± 29.24) % and (60.98 ± 35.96) % for 3 days, 3 months, 6 months, 12 months and 24 months after surgery, respectively. There were 2 cases of SSI (surgical site infection), 1 case of NI (neurovascular injury) and 1 case of cerebrospinal fluid (CSF) leakage. Conclusions: This study highlights a safe and effective technique, the gantry crane technique, for treating severe thoracic spinal stenosis and myelopathy caused by TOLF. [ABSTRACT FROM AUTHOR]

Objective: Pediatric nonsaccular aneurysms are rare but challenging lesions; pipeline embolization devices (PEDs) are their potential treatment option. In this study, we aimed to evaluate the safety and efficacy of PEDs for treatment of these aneurysms. Methods: We retrospectively selected pediatric patients with nonsaccular aneurysms treated using PEDs between June 2015 and July 2021 from our prospectively maintained database. For each patient, demographics, aneurysm characteristics, procedure details, and clinical and angiographic follow-up data were collected and summarized. Results: This study included 16 pediatric patients with 16 nonsaccular aneurysms treated with PEDs. A median clinical follow-up time of 1,376 days was achieved in 93.75% of the patients. The complication rate of the included patients was 25%, with two patients developing mass eect, one patient undergoing major ischemic stroke, and one patient experiencing stent foreshortening after the procedure. The complete occlusion rate of aneurysms without any neurologic sequelae was 93.33%, with a median angiographic follow-up period of 246 days. The mortality rate was 6.25%. Conclusions: The use of PEDs to treat pediatric nonsaccular aneurysms is feasible, with a high rate of complete occlusion of the aneurysm and favorable follow-up outcomes. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformation (CCM) is a neurovascular disease that can lead to seizures and stroke-like symptoms. The familial form is caused by a heterozygous germline mutation in either the CCM1, CCM2, or CCM3 gene. While the importance of a second-hit mechanism in CCM development is well established, it is still unclear whether it immediately triggers CCM development or whether additional external factors are required. We here used RNA sequencing to study differential gene expression in CCM1 knockout induced pluripotent stem cells (CCM1−/− iPSCs), early mesoderm progenitor cells (eMPCs), and endothelial-like cells (ECs). Notably, CRISPR/Cas9-mediated inactivation of CCM1 led to hardly any gene expression differences in iPSCs and eMPCs. However, after differentiation into ECs, we found the significant deregulation of signaling pathways well known to be involved in CCM pathogenesis. These data suggest that a microenvironment of proangiogenic cytokines and growth factors can trigger the establishment of a characteristic gene expression signature upon CCM1 inactivation. Consequently, CCM1−/− precursor cells may exist that remain silent until entering the endothelial lineage. Collectively, not only downstream consequences of CCM1 ablation but also supporting factors must be addressed in CCM therapy development. [ABSTRACT FROM AUTHOR]

Hypertension, a multifactorial chronic inflammatory condition, is an important risk factor for neurovascular and neurodegenerative diseases, including stroke and Alzheimer's disease. These diseases have been associated with higher concentrations of circulating interleukin (IL)-17A. However, the possible role that IL-17A plays in linking hypertension with neurodegenerative diseases remains to be established. Cerebral blood flow regulation may be the crossroads of these conditions because regulating mechanisms may be altered in hypertension, including neurovascular coupling (NVC), known to participate in the pathogenesis of stroke and Alzheimer's disease. In the present study, the role of IL-17A on NVC impairment induced by angiotensin (Ang) II in the context of hypertension was examined. Neutralization of IL-17A or specific inhibition of its receptor prevents the NVC impairment (p < 0.05) and cerebral superoxide anion production (p < 0.05) induced by Ang II. Chronic administration of IL-17A impairs NVC (p < 0.05) and increases superoxide anion production. Both effects were prevented with Tempol and NADPH oxidase 2 gene deletion. These findings suggest that IL-17A, through superoxide anion production, is an important mediator of cerebrovascular dysregulation induced by Ang II. This pathway is thus a putative therapeutic target to restore cerebrovascular regulation in hypertension. [ABSTRACT FROM AUTHOR]

Getting older affects both the structure of the brain and some cognitive capabilities. Until now, magnetic resonance imaging (MRI) approaches have been unable to give a coherent reflection of the cognitive declines. It shows the limitation of the contrast mechanisms used in most MRI investigations, which are indirect measures of brain activities depending on multiple physiological and cognitive variables. However, MRI signals may contain information of brain activity beyond these commonly used signals caused by the neurovascular response. Here, we apply a zero-spin echo (ZSE) weighted MRI sequence, which can detect heartbeat-evoked signals (HES). Remarkably, these MRI signals have properties only known from electrophysiology. We investigated the complexity of the HES arising from this sequence in two age groups; young (18–29 years) and old (over 65 years). While comparing young and old participants, we show that the complexity of the HES decreases with age, where the stability and chaoticity of these HES are particularly sensitive to age. However, we also found individual differences which were independent of age. Complexity measures were related to scores from different cognitive batteries and showed that higher complexity may be related to better cognitive performance. These findings underpin the affinity of the HES to electrophysiological signals. The profound sensitivity of these changes in complexity shows the potential of HES for understanding brain dynamics that need to be tested in more extensive and diverse populations with clinical relevance for all neurovascular diseases. [ABSTRACT FROM AUTHOR]

Objectives: Photon-counting detector computed tomography (PCD-CT) is a promising new technique for CT imaging. The aim of the present study was the in vitro comparison of coil-related artifacts in PCD-CT and conventional energy-integrating detector CT (EID-CT) using a comparable standard brain imaging protocol before and after metal artifact reduction (MAR). Methods: A nidus-shaped rubber latex, resembling an aneurysm of the cerebral arteries, was filled with neurovascular platinum coils and inserted into a brain imaging phantom. Image acquisition and reconstruction were repeatedly performed for PCD-CT and EID-CT (n = 10, respectively) using a standard brain imaging protocol. Moreover, linear interpolation MAR was performed for PCD-CT and EID-CT images. The degree of artifacts was analyzed quantitatively (standard deviation in a donut-shaped region of interest) and qualitatively (5-point scale analysis). Results: Quantitative and qualitative analysis demonstrated a lower degree of metal artifacts in the EID-CT images compared to the total-energy PCD-CT images (e.g., 82.99 ± 7.89 Hounsfield units (HU) versus 90.35 ± 6.28 HU; p < 0.001) with no qualitative difference between the high-energy bin PCD-CT images and the EID-CT images (4.18 ± 0.37 and 3.70 ± 0.64; p = 0.575). After MAR, artifacts were more profoundly reduced in the PCD-CT images compared to the EID-CT images in both analyses (e.g., 2.35 ± 0.43 and 3.18 ± 0.34; p < 0.001). Conclusion: PCD-CT in combination with MAR have the potential to provide an improved option for reduction of coil-related artifacts in cerebral imaging in this in vitro study. Key Points: • Photon-counting detector CT produces more artifacts compared to energy-integrating detector CT without metal artifact reduction in cerebral in vitro imaging after neurovascular coil-embolization. • Spectral information of PCD-CT provides the potential for new post-processing techniques, since the coil-related artifacts were lower in PCD-CT images compared to EID-CT images after linear interpolation metal artifact reduction in this in vitro study. [ABSTRACT FROM AUTHOR]

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Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during retinal development. In certain retinal diseases, the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea). Furthermore, continuously activated microglia secrete inflammatory factors and expedite the loss of the blood-retinal barrier which causes irreversible damage to the secondary death of neurons. In this review, we support microglia can be a potential cellular therapeutic target in retinopathy. We briefly describe the relevance of microglia to the retinal vasculature and blood-retinal barrier. Then we discuss the signaling pathway related to how microglia move to their destinations and regulate vascular regeneration. We summarize the properties of microglia in different retinal disease models and propose that reducing the number of pro-inflammatory microglial death and conversing microglial phenotypes from pro-inflammatory to anti-inflammatory are feasible for treating retinal neovascularization and the damaged blood-retinal barrier (BRB). Finally, we suppose that the unique properties of microglia may aid in the vascularization of retinal organoids. [ABSTRACT FROM AUTHOR]

Objective: Describe and discuss a typical case with recurrent painful ophthalmoplegic neuropathy (RPON), and demonstrate a likely extrinsic compression of the sixth cranial nerve by a vascular loop. Background: RPON is a rare, but well-known entity, characterized by attacks of ophthalmoplegia associated with ipsilateral headache. The etiology is unknown, but a neurovascular conflict (NVC) has been suggested as a cause. Method: A 62-year-old woman presented in the emergency department with a horizontal diplopia that developed a few hours after the onset of a left temporal headache. In the past she had presented to the clinic with the same problem several times. She had been thoroughly examined, but no cause had been found. The symptoms had resolved by themselves. In addition to a classic finding in RPON, gadolinium enhancement and thickening of a cranial nerve, the new MRI scanning detected an NVC. Herein we discuss the relevance of this finding. Conclusion: A neurovascular conflict causing inflammatory demyelination of a single cranial nerve and relapsing remitting painful ophthalmoplegic neuropathy is an alluring idea. However, it is hard to conceive theoretically, and more reported cases with compelling data are needed to give credibility to such an idea. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tooth avulsion clinically presents as complete displacement of a tooth from the alveolar socket and it is one of the most severe forms of dental trauma leading to compromised neurovascular supply, loss of periodontal ligament and pulp necrosis. Storing of avulsed tooth in appropriate storage medium to preserve the periodontal cell viability is of prime importance and research to find the appropriate storage media is still on. AIM: The aim of this study was to investigate the effects of green tea and turmeric as a storage media on periodontal cell viability. MATERIALS AND METHODS: This was a prospective, randomized study conducted using sixty single rooted human premolars freshly extracted for orthodontic purpose. Selected subjects were divided into three groups of 20 each. Randomization was done by performing simple random sampling; Group A consisted of teeth to be stored in HBSS, Group B included teeth to be stored in Green tea and Group C included teeth to be store in Turmeric. Periodontal cell viability was assessed by using a Neubauer's chamber under the light microscope after two hours interval. RESULTS: HBSS preserved significantly higher number of viable PDL cells than any other storage solutions. Green tea extract showed better cell viability in comparison with turmeric. CONCLUSION: The present study indicates that HBSS and green tea effectively maintains the viability of PDL for two hours. Turmeric is less effective in preserving the PDL cell viability within the study time interval. [ABSTRACT FROM AUTHOR]

Purpose: Understanding the anatomy of the deep neurovascular structures of the hand is essential in surgical planning. There is a lack of literature regarding hand size and its influence in branching variation and the distances between branches of various neurovascular structures. Our study quantifies the variation in branching distances of the deep ulnar nerve and deep palmar arch branches. Methods: Twenty-five fresh-frozen cadaveric hands were dissected. Each branch of the deep ulnar nerve and deep palmar arch was identified. The distance from the most distal portion of the pisiform to the proximal aspect of the branch was measured. The relationship between the length of the third metacarpal and the distance of each branch from the pisiform was examined. Results: There was no relationship between branching differences in the deep ulnar nerve and the length of the third metacarpal. There was a significant association between the length of the third metacarpal and the second, third, and fourth branches of the deep palmar arch (p < 0.05). Conclusions: Our study found a significant association between the branching distances of the second, third, and fourth branches of the deep palmar arch and hand size as measured by the length of the third metacarpal. [ABSTRACT FROM AUTHOR]

Talus fractures are rare (<1% of all fractures), and their rarity limits the number of studies available to guide management. In instances such as this, cadaveric studies can play an important role. The purpose of this scoping review was to identify and describe the current body of literature on cadaveric studies of fractures of the talus. Through multiple electronic database searches (Medline, Embase, Scopus) we identified a broad body of cadaveric research into talus fractures, and these were classified into 4 main themes. Study characteristics were summarised along with any descriptive results and conclusions. The search yielded 484 articles of which 19 met the inclusion criteria. They provide valuable insights into benefits and drawbacks of surgical approaches to the talus, particularly with regard to direct visualisation of anatomic reduction, and risks of neurovascular or tendon compromise. For talar neck fractures it is clear that cannulated screws offer superior fixation over plates, however, are inferior when considering anatomic reduction of the fracture. Direct visualisation of fracture reduction is far superior to intraoperative radiographic assessment, and mal-reduction leads to reduced subtalar joint range of motion, midfoot deformity, and increased joint contact pressures. This study provides a summary of the existing literature surrounding the use of cadaver studies in fractures of the talus. We have identified gaps in the literature, particularly surrounding strength of fixation of new locking plate fixation techniques. [ABSTRACT FROM AUTHOR]

The exploration of human brain function has always been a research hotspot in the field of neuroscience. The concept of a neurovascular unit suggests that cerebral microcirculation can be used as a reliable signal to reflect neural function. Accordingly, functional imaging techniques based on the neurovascular unit are very promising because of their ability to reveal neurovascular coupling and evaluate the functional rehabilitation of cerebrovascular diseases represented by stroke. In the present review, we first describe the role of the neurovascular unit in the injury and repair processes after stroke. We then briefly introduce the relative characteristics and advantages of representative neurovascular unit-based functional imaging. Finally, we summarized the value of these techniques in the evaluation of neural networks after stroke. [ABSTRACT FROM AUTHOR]

Brain perivascular macrophages (PVMs) are attracting increasing attention as this emerging cell population in the brain has multifaced roles in supporting the central nervous system structure, brain development, and maintaining physiological functions. They also widely participate in neurological diseases such as neurodegeneration and ischemic stroke. Moreover, PVMs have been reported to have both beneficial and detrimental effects under different pathological contexts. Advanced research technologies allowed the further in‐depth study of PVMs and revealed novel concepts in their origins, differentiation, and regulatory mechanisms. Deepened understanding of the roles of PVMs in different brain pathological conditions can reveal novel phenotypic changes and regulatory signaling, which might pave the way for the development of novel treatment strategies targeting PVMs. [ABSTRACT FROM AUTHOR]

Background: Recently, a data‐driven regression analysis method was developed to utilize the resting‐state (rs) blood oxygenation level–dependent signal for cerebrovascular reactivity (CVR) mapping (rs‐CVR), which was previously optimized by comparing with the CO2 inhalation‐based method in health subjects and patients with neurovascular diseases. Purpose: To investigate the agreement of rs‐CVR and the CVR mapping with breath‐hold MRI (bh‐CVR) in patients with gliomas. Study Type: Retrospective. Population: Twenty‐five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas. Field Strength/Sequence: Dynamic T2*‐weighted gradient‐echo echo‐planar imaging during a breath‐hold paradigm and during the rs on a 3‐T scanner. Assessment: rs‐CVR with various frequency ranges and resting‐state fluctuation amplitude (RSFA) were assessed. The agreement between each rs‐based CVR measurement and bh‐CVR was determined by voxel‐wise correlation and Dice coefficient in the whole brain, gray matter, and the lesion region of interest (ROI). Statistical Tests: Voxel‐wise Pearson correlation, Dice coefficient, Fisher Z‐transformation, repeated‐measure analysis of variance and post hoc test with Bonferroni correction, and nonparametric repeated‐measure Friedman test and post hoc test with Bonferroni correction were used. Significance was set at P < 0.05. Results: Compared with bh‐CVR, the highest correlations were found at the frequency bands of 0.04–0.08 Hz and 0.02–0.04 Hz for rs‐CVR in both whole brain and the lesion ROI. RSFA had significantly lower correlations than did rs‐CVR of 0.02–0.04 Hz and a wider frequency range (0–0.1164 Hz). Significantly higher correlations and Dice coefficient were found in normal tissues than in the lesion ROI for all three methods. Data Conclusion: The optimal frequency ranges for rs‐CVR are determined by comparing with bh‐CVR in patients with gliomas. The rs‐CVR method outperformed the RSFA. Significantly higher correlation and Dice coefficient between rs‐ and bh‐CVR were found in normal tissue than in the lesion. Level of Evidence: 3 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background: Migraine and stroke are neurovascular diseases that have become a public health problem and a relatively high economic burden. The relationship between migraine and stroke has been described in the literature for a long time. Several studies reveal that migraine can be a risk factor for stroke. Methods: We systematically searched PubMed using the PRISMA method and keywords according to MeSH terms to prepare this systematic review. We included published articles discussing migraine as a risk factor for ischemic stroke with a cohort study design and English article and listed the statistical value of the study. Results: In our meta-analysis, we found that migraine significantly increases the incidence of ischemic stroke. There were 12 studies included in this systematic review, and a meta-analysis was performed. The results showed a significant association between migraine and ischemic stroke (HR 1.205, 95% CI 1.151-1.262 p = 0.000), migraine with aura and ischemic stroke (HR 1.442, 95% CI 1.241-1.675 p = 0.000), and migraine without aura and ischemic stroke (HR 1.126, 95% CI 1.048-1.211 p = 0.001). The exact mechanism of stroke caused by migraine is still unclear, although, in some theories, several mechanisms have been described that are thought to be the cause of stroke. Several important points of the cause of stroke in migraine are hemodynamic changes, endothelial dysfunction, cervical artery dissection, vascular reactivity, hypercoagulability, and abortive migraine drugs. Conclusions: Both migraine with aura and without aura are risk factors for ischemic stroke. Several mechanisms that may cause ischemic stroke in migraine have been described, of which CSD-induced endothelial dysfunction is the primary pathophysiology of ischemic stroke in migraine. [ABSTRACT FROM AUTHOR]

Introduction: Retinopathy of prematurity (ROP) is considered a neurovascular disease. We investigated whether ROP, mild or severe, is associated with neurodevelopmental impairment (NDI) in extremely preterm children. Methods: We conducted a multicenter retrospective cohort study in southern Taiwan. A total of 394 children <28 weeks of gestation who survived to discharge from 2011 to 2018 received neurodevelopmental assessment at corrected age of 24 months. Severe ROP was defined as ROP of stages 2 plus or worse, or recipients of retinal therapy, and mild ROP as stage 1 or 2 in at least one eye. NDI was defined as cognitive or motor impairment using the Bayley Scales of Infant and Toddler Development, moderate to severe cerebral palsy, or profound hearing loss. Results: Among the 374 children validated for analysis, 157 children (42%) had non-ROP, 145 (39%) mild ROP, and 72 (19%) severe ROP. As ROP severity increased progressively from non-ROP, to mild ROP, and to severe ROP, the rates of NDI increased from 25%, to 46%, and to 61%. The multivariable logistic regression showed that the model included three levels of ROP, and neonatal morbidities achieved better overall performance for NDI than the model that included neonatal morbidities alone. Compared with non-ROP, mild ROP and severe ROP had adjusted odds ratios of 1.90 (95% CI: 1.10–3.28) and 2.75 (95% CI: 1.33–5.67) for NDI, respectively. Conclusion: Mild ROP and severe ROP are independent neonatal morbidities associated with NDI. Neurodevelopmental follow-up of extremely preterm children with any stage of ROP is needed. [ABSTRACT FROM AUTHOR]

Purpose: No study has documented the oculomotor nerve (OMN) segment lying between the posterior cerebral (PCA) and superior cerebellar (SCA) arteries adjacent to the brainstem. The present study aimed to characterize it. Methods: A total of 71 patients underwent thin-sliced, sagittal T2-weighted magnetic resonance imaging for analysis. Results: The OMN segments lying between the PCA and SCA were identified in all patients. The OMN segment in relation to the PCA and SCA was classified into five types. Of them, the PCA-OMN contact type was the most frequent and found in 35.2% of 71 sides on the right and 39.4% on the left. Also, the PCA-OMN compression type was identified in 12.7% on the right and 15.5% on the left. In these types, the mean distance between the brainstem and contact/compression sites were measured 4.4 ± 2.3 mm on the right and 4.4 ± 1.6 mm on the left. In more than forty percent, the sites were located at the level of the pontomesencephalic junction. Conclusions: The OMN may be frequently in contact with the PCA near the brainstem. The site located more distal than the central-peripheral myelin junction of the OMN can attribute to a low frequency of neurovascular compression syndrome of the nerve. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformation (CCM) is a neurovascular disease that affects 0.5% of the general population. For a long time, CCM research focused on genetic mutations, endothelial junctions and proliferation, but recently, transcriptome and proteome studies have revealed that the hemostatic system and neuroinflammation play a crucial role in the development and severity of cavernomas, with some of these publications coming from our group. The aim of this review is to give an overview of the latest molecular insights into the interaction between CCM-deficient endothelial cells with blood components and the neurovascular unit. Specifically, we underscore how endothelial dysfunction can result in dysregulated hemostasis, bleeding, hypoxia and neurological symptoms. We conducted a thorough review of the literature and found a field that is increasingly poised to regard CCM as a hemostatic disease, which may have implications for therapy. [ABSTRACT FROM AUTHOR]

Pericytes, like vascular smooth muscle cells, are perivascular cells closely associated with blood vessels throughout the body. Pericytes are necessary for vascular development and homeostasis, with particularly critical roles in the brain, where they are involved in regulating cerebral blood flow and establishing the blood-brain barrier. A role for pericytes during neurovascular disease pathogenesis is less clear--while some studies associate decreased pericyte coverage with select neurovascular diseases, others suggest increased pericyte infiltration in response to hypoxia or traumatic brain injury. Here, we used an endothelial loss-of-function Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)/Notch mediated mouse model of brain arteriovenous malformation (AVM) to investigate effects on pericytes during neurovascular disease pathogenesis. We tested the hypothesis that pericyte expansion, via morphological changes, and Platelet-derived growth factor B/Platelet-derived growth factor receptor β (Pdgf-B/Pdgfrβ)-dependent endothelial cell-pericyte communication are affected, during the pathogenesis of Rbpj mediated brain AVM in mice. Our data show that pericyte coverage of vascular endothelium expanded pathologically, to maintain coverage of vascular abnormalities in brain and retina, following endothelial deletion of Rbpj. In Rbpj-mutant brain, pericyte expansion was likely attributed to cytoplasmic process extension and not to increased pericyte proliferation. Despite expanding overall area of vessel coverage, pericytes from Rbpj-mutant brains showed decreased expression of Pdgfrβ, Neural (N)-cadherin, and cluster of differentiation (CD)146, as compared to controls, which likely affected Pdgf-B/Pdgfrβ-dependent communication and appositional associations between endothelial cells and pericytes in Rbpj-mutant brain microvessels. By contrast, and perhaps by compensatory mechanism, endothelial cells showed increased expression of N-cadherin. Our data identify cellular and molecular effects on brain pericytes, following endothelial deletion of Rbpj, and suggest pericytes as potential therapeutic targets for Rbpj/Notch related brain AVM. [ABSTRACT FROM AUTHOR]

Purpose: This study compared screw and Kirschner-wire (K-wire) fixation for intra-articular fractures of the proximal phalanx head regarding the success of union and functional outcomes. Methods: In this retrospective study, we enrolled patients with closed intra-articular fractures of the proximal phalangeal head treated between January 2011 and December 2021. Patients with open wounds, tendon or neurovascular injuries, comminuted fractures, or middle phalangeal fractures were excluded. Patients' demographics, bone union, proximal interphalangeal (PIP) joint range of motion (ROM), grip power, and complications were collected and analyzed. The percentage of intra-articular surface involvement and the number of bone fragments were also analyzed in relation to the functional results. Results: Among 41 patients, 21 were managed with screw fixation, and the remaining 20 with K-wire fixation. The mean union rate was 100% in the screw fixation group and 95.0% in the K-wire fixation group, with no statistically significant difference (p=0.488). Other functional parameters (PIP joint ROM, time to bone union, and grip power) were not significantly different between the two groups. Regardless of the treatment modality, the PIP joint ROM showed significant negative associations with the involvement of more intra-articular surfaces (p<0.001) and the presence of a greater number of bone fragments (p=0.040). Conclusion: In intra-articular fractures of the proximal phalanx head, the treatment modality (screw or K-wire) did not affect the treatment outcome. Instead, the percentage of intra-articular surface involvement and the number of bone fragments showed significant negative associations with the PIP joint ROM after treatment. [ABSTRACT FROM AUTHOR]

Background and purpose: Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non‐traditional vascular risk factors (nt‐vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t‐vrfs). In order to discover sex‐specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10‐year trends in the prevalence of vrfs in Switzerland were assessed. Methods: Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t‐vrfs and nt‐vrfs were analyzed in a cross‐sectional study design. Results: Over the observation period, the number of women having full‐time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt‐vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t‐vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t‐vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]). Conclusions: A rise in women's economic participation alongside a higher affection with nt‐vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Bioinformatics tools are used to create a clinical prediction model for cervical cancer metastasis and to investigate the neurovascular-related genes that are involved in brain metastasis of cervical cancer. One hundred eighteen patients with cervical cancer were divided into two groups based on the presence or absence of metastases, and the clinical data and imaging findings of the two groups were compared retrospectively. The nomogram-based model was successfully constructed by taking into account four clinical characteristics (age, stage, N, and T) as well as one imaging characteristic (original_glszm_GrayLevelVariance Rad-score). In patients with cervical cancer, headaches and vomiting were more often reported in the brain metastasis group than in the other metastasis groups. According to the TCGA data, mRNA differential gene expression analysis of patients with cervical cancer revealed an increase in the expression of neurovascular-related gene Adrenoceptor Beta 1 (ADRB1) in the brain metastasis group. An analysis of the correlation between imaging features and ADRB1 expression revealed that ADRB1 expression was significantly higher in the low Rad-score group compared with the high Rad-score group (P = 0.025). Therefore, ADRB1 expression in cervical cancer was correlated with imaging features and was associated as a risk factor for cerebral neurovascular metastases. This study developed a nomogram prediction model for cervical cancer metastasis using age, stage, N, T and original_glszm_GrayLevelVariance. As a risk factor associated with the development of cerebral neurovascular metastases of cervical cancer, ADRB1 expression was significantly higher in brain metastases from cervical cancer. [ABSTRACT FROM AUTHOR]

In the pathophysiology of hemorrhagic stroke, the perturbation of the neurovascular unit (NVU), a functional group of the microvascular and brain intrinsic cellular components, is implicated in the progression of secondary injury and partially informs the ultimate patient outcome. Given the broad NVU functions in maintaining healthy brain homeostasis through its maintenance of nutrients and energy substrates, partitioning central and peripheral immune components, and expulsion of protein and metabolic waste, intracerebral hemorrhage (ICH)-induced dysregulation of the NVU directly contributes to numerous destructive processes in the post-stroke sequelae. In ICH, the damaged NVU precipitates the emergence and evolution of perihematomal edema as well as the breakdown of the blood–brain barrier structural coherence and function, which are critical facets during secondary ICH injury. As a gateway to the central nervous system, the NVU is among the first components to interact with the peripheral immune cells mobilized toward the injured brain. The release of signaling molecules and direct cellular contact between NVU cells and infiltrating leukocytes is a factor in the dysregulation of NVU functions and further adds to the acute neuroinflammatory environment of the ICH brain. Thus, the interactions between the NVU and immune cells, and their reverberating consequences, are an area of increasing research interest for understanding the complex pathophysiology of post-stroke injury. This review focuses on the interactions of T-lymphocytes, a major cell of the adaptive immunity with expansive effector function, with the NVU in the context of ICH. In cataloging the relevant clinical and experimental studies highlighting the synergistic actions of T-lymphocytes and the NVU in ICH injury, this review aimed to feature emergent knowledge of T cells in the hemorrhagic brain and their diverse involvement with the neurovascular unit in this disease. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations (CMs) are slow-flow vascular lesions that affect up to 0.5% of the pediatric population. These lesions are at risk for hemorrhage, causing seizures, and leading to neurological deficits. Here, we conduct a literature review and then present a report of a supratentorial CM in a 2-year-old patient with no significant past medical history who presented at our institution with 1 month of eye twitching. We performed a literature search of five databases of all articles published before 2020. Our inclusion criteria included cohort and case series of children with mean age under 12 years. Our search yielded 497 unique articles, of which 16 met our inclusion criteria. In our pooled literature analysis, a total of 558 children were included, 8.3% of which had a positive family history and 15.9% had multiple CMs. About 46.1% of the children had seizures, and 88.4% of those who underwent surgery had a total resection. About 85.1% of those with epilepsy were Engel Class 1 postsurgery. Over a mean follow-up of 4.1 years, 3.4% of patients had additional neurological deficits, including paresis and speech deficits. Our analysis of published literature shows surgical intervention should be considered first-line therapy for patients who are symptomatic from CM, present with seizure, and have surgically accessible lesions. Additional work is needed on outcomes and long-term effects of minimally invasive treatments, including radiosurgery and laser ablation, in pediatric populations. [ABSTRACT FROM AUTHOR]

In this preliminary study, the underlying pathophysiology mechanisms of cerebral aneurysms (CAs) in monozygotic twins (MTs) were investigated via a rare pair of MTs (twin A and twin B) involving four reconstructed arterial models using preclinical information. First, dimensions and configurated outlines of three-perspective geometries were compared. Adopting an in-vitro validated numerical CA model, hemodynamic characteristics were investigated in the MTs, respectively. Despite expected genetic similarities, morphological comparisons show that configurations of cerebral arteries exhibit significant differences between the twins. The ICA size of twin A is larger than that in twin B (2.23~25.86%), varying with specific locations, attributing to variations during embryological developments and environmental influences. Numerical modeling indicates the MTs have some hemodynamic similarities such as pressure distributions (~13,400 Pa) and their oscillatory shear index (OSI) (0~0.49), but present significant differences in local regions. Specifically, the difference in blood flow rate in the MTs is from 16% to 221%, varying with specifically compared arteries. The maximum time-averaged wall shear stress (53.6 Pa vs. 37.8 Pa) and different local OSI distributions were also observed between the MTs. The findings revealed that morphological variations in MTs could be generated by embryological and environmental factors, further influencing hemodynamic characteristics on CA pathophysiology.

Tortuosity and fragility of the intracranial vasculature have precluded the application of novel intravascular imaging modalities during the treatment of cerebrovascular pathologies. In other circulatory beds, these technologies have transformed clinical and therapeutic decision-making. A new report demonstrates the clinical use of high-resolution intravascular imaging in the human cerebrovasculature using neuro optical coherence tomography. This technology provides an unprecedented opportunity to examine the luminal dimensions of cerebrovascular disease. We expect that the neurointerventional community will rapidly adopt this technology—similar to wider adoptions by other vascular specialties—for both a better understanding of underlying disease and clarity of endovascular therapeutic safety and effectiveness. [ABSTRACT FROM AUTHOR]

Cerebral X-ray digital subtraction angiography (DSA) is a widely used imaging technique in patients with neurovascular disease, allowing for vessel and flow visualization with high spatio-temporal resolution. Automatic artery–vein segmentation in DSA plays a fundamental role in vascular analysis with quantitative biomarker extraction, facilitating a wide range of clinical applications. The widely adopted U-Net applied on static DSA frames often struggles with disentangling vessels from subtraction artifacts. Further, it falls short in effectively separating arteries and veins as it disregards the temporal perspectives inherent in DSA. To address these limitations, we propose to simultaneously leverage spatial vasculature and temporal cerebral flow characteristics to segment arteries and veins in DSA. The proposed network, coined CAVE, encodes a 2D+time DSA series using spatial modules, aggregates all the features using temporal modules, and decodes it into 2D segmentation maps. On a large multi-center clinical dataset, CAVE achieves a vessel segmentation Dice of 0.84 (± 0.04) and an artery–vein segmentation Dice of 0.79 (± 0.06). CAVE surpasses traditional Frangi-based k -means clustering (P < 0.001) and U-Net (P < 0.001) by a significant margin, demonstrating the advantages of harvesting spatio-temporal features. This study represents the first investigation into automatic artery–vein segmentation in DSA using deep learning. The code is publicly available at https://github.com/RuishengSu/CAVE_DSA. [Display omitted] • The first automatic deep learning-based method for artery–vein segmentation in DSA is proposed. • CAVE generates artery–vein segmentations from 2D+time DSA series with variable frame lengths. • CAVE simultaneously harnesses spatial vasculature and temporal contrast flow characteristics. • CAVE promises to facilitate fast, accurate, and objective vasculature interpretation in DSA. [ABSTRACT FROM AUTHOR]

Retinoic acid is a metabolic product derived from vitamin A, acting at a nuclear level to maintain the proper transcriptional activity. Moreover, this molecule contributes to the development and maturation of the cerebral vascular system, playing a pivotal role in development and maintenance of neurovascular unit integrity. This physiological structure is comprised of glial cells, vascular cells, and neurons, ensuring the correct function of the blood-brain barrier and, at last instance, the homeostasis of the central nervous system. Therefore, retinoic acid ensures the physiological structure integrity of the neurovascular unit, decreasing the development of neurological disorders. Furthermore, retinoic acid can modulate the physiological function of the neurovascular unit cells, which is crucial to the maintenance of this physiological structure. The deletion of this molecule leads to the development of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease. In addition, impaired signaling of this molecule contributes to a worse prognosis in the recovery after ischemic stroke. This review characterizes the cellular components that constitute the neurovascular unit and analyzes the effect of retinoic acid on these cellular components that, in a coordinated manner, are responsible for homeostasis of the central nervous system. Through this description, it seems apparent that retinoic acid administration might be an essential pharmacological tool in the near future. • Retinoic acid promotes neuronal regulation and differentiation. • Retinoic acid modulates the inflammatory response of astrocytes and microglia. • Retinoic acid controls endothelial-pericyte interactions. • Retinoic acid induces the contractile phenotype of smooth muscle cells. • Retinoic acid promotes re-myelination of damaged oligodendrocytes. [ABSTRACT FROM AUTHOR]

Objective: To assess the accuracy of routine knee MRI in detecting acute popliteal artery and/or common peroneal nerve (CPN) dysfunction following multiligamentous knee injury (MLKI), with correlation of MRI findings to clinical outcome. Materials and methods: Routine MRI knee examinations in 115 MLKI patients (54/115 with acute neurovascular injury, 61/115 without neurovascular injury) were retrospectively reviewed. Cases were classified by injury mechanism and ligamentous injuries sustained. MRI examinations were reviewed by two readers for vascular (arterial flow void, arterial calibre, intimal flap, perivascular hematoma) and CPN (intraneural T2-hyperintensity, calibre, discontinuity, perineural hematoma) injuries. Accuracy of routine knee MRI in the diagnosis of acute neurovascular injury and correlation of MRI findings to clinical outcome were evaluated. Results: Patients included 86/115 males, mean age 33 years. The accuracy of MRI in diagnosis of acute CPN injury was 80.6%, 83.6% (readers 1 and 2): sensitivity (78%, 79.7%), specificity (80%, 86.7%), PPV (78%, 82.5%), and NPV (82.7%, 84.4%). Increased intraneural T2 signal showed a significant correlation to acute CPN dysfunction (p < 0.05). MRI was 75%, 69.8% (readers 1 and 2) accurate in detecting acute vascular injury: sensitivity (73.3%, 86.7%), specificity (75.2%, 67.3%), PPV (30.5%, 36.1%), and NPV (95%, 97.1%). No MRI features of vascular injury showed a statistical correlation with clinical outcome. Neurovascular complications were more common in ultra-low-energy injuries and KD-V3L pattern of ligament disruption. Conclusion: Routine MRI is of limited accuracy in assessing vascular complication, but higher accuracy in assessing CPN injury following MLKI. Increased intraneural T2 signal on conventional knee MR imaging shows statistically significant association with clinically documented acute CPN dysfunction following MLKI. [ABSTRACT FROM AUTHOR]

Background: Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II is an autosomal recessive condition encompassing a heterogeneous group of disorders characterized by symmetrical growth retardation leading to dwarfism, microcephaly, and a range of multiple medical complications including neurovascular diseases. Biallelic pathogenic variants in the pericentrin gene (PCNT) have been implicated in its pathogenesis. Case presentation: We performed whole-exome sequencing to ascertain the diagnosis of a 2 year and 6 months old boy who presented with severe failure to thrive, microcephaly, and facial gestalt suggestive of MOPD Type II which included features such as retrognathia, small ears, prominent nasal root with a large nose, microdontia, sparse scalp hair, bilateral fifth finger clinodactyly. He had a small ostium secundum atrial septal defect and bilaterally small kidneys. Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II was confirmed based on a pathogenic compound heterozygous frameshift variant in the PCNT gene c.5059_5060delAA | p. Asn1687fs (novel variant) and c.9535dup (p. Val3179fs). His parents were found to be heterozygous carriers for the variants. Conclusion: We report a novel frameshift variant in the PCNT gene and a previously unreported phenotype for Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II. [ABSTRACT FROM AUTHOR]

Objectives: Ischemic cerebral infarction (ICI) is a fatal neurovascular disorder. A bioinformatics approach based on single-cell and bulk RNA-seq analyses was applied to investigate the pathways and genes involved in ICI and study the expression profile of these genes. Methods: First, the aberrantly regulated "small-molecule ribonucleic acids" [microRNA (miRNAs)] and messenger RNAs (mRNAs) were analyzed using transcriptome data from the ischemic brain infarction dataset of the Gene Expression Omnibus (GEO) database. In mouse cerebrovascular monocytes, the single-cell regulatory network inference and clustering (SCENIC) workflow was used to identify key transcription factors (TFs). Then, the two miRNA-TF-mRNA interaction networks were constructed. Moreover, the molecular complex detection (MCODE) extracted the core sub-networks and identified the important TFs within these sub-networks. Finally, whole blood samples were collected for validation of the expression of critical molecules in ICI. Results: We identified four cell types and 266 regulons in mouse cerebrovascular monocytes using SCENIC analysis. Moreover, 112 differently expressed miRNAs and 3,780 differentially expressed mRNAs were identified. We discovered potential biomarkers in ICI by building a miRNA-TF-mRNA interaction network. The hsa-miR-518-5p/hsa-miR-3135b/REL/SOD2 was found to play a potential role in ICI progression. The expression of REL and superoxide dismutase 2 (SOD2) was significantly elevated in the ICI group in the clinical cohort (P < 0.05). Furthermore, a REL expression was elevated in endothelial cells and fibroblasts at the single-cell level, indicating that REL is a cell-specific regulon. Functional enrichment analyses revealed that REL is primarily engaged in neurotransmitter activity and oxidative phosphorylation. Conclusions: Our research uncovered novel biomarkers for ICI of neurovascular disease. The hsa-miR-518-5p/hsa-miR-3135b may regulate the REL/SOD2 pathway in ICI progression. [ABSTRACT FROM AUTHOR]

Objectives: Various informant-based questionnaires are used in clinical practice to screen for pre-stroke cognitive problems. However, there is no guidance on which tool should be preferred. We compared the validity of the two most commonly used informant-based tools.Methods: We recruited consecutively admitted stroke patients. Patients' informants completed the Informant Questionnaire for Cognitive Decline in the Elderly Short Form (IQCODE-SF, 16-item) and Ascertain Dementia 8 (AD8). We assessed construct validity (accuracy) against a semi-structured clinical interview for dementia or mild cognitive impairment (MCI), describing test accuracy metrics and comparing area under ROC curves (AUROC). We described criterion validity by evaluating associations between test scores and neuroimaging markers of dementia and overall 'brain frailty'. Finally, we described prognostic validity comparing ROC curves for 18-month clinical outcomes of dementia, death, stroke, and disability.Results: One-hundred-thirty-seven patient-informant dyads were recruited. At usual clinical cut-points, the IQCODE-SF had comparable sensitivity to the AD8 (both = 92%) for pre-stroke dementia, but superior specificity (IQCODE-SF: 82% vs. AD8: 58%). Youden index suggested that the optimal AD8 threshold for diagnosis of dementia is ≥4. The IQCODE-SF demonstrated stronger associations with markers of generalised and medial-temporal lobe atrophy, neurovascular disease, and overall brain frailty. IQCODE-SF also demonstrated greater accuracy for predicting future dementia (IQCODE-SF AUROC = 0.903, 95% CI = 0.798-1.00; AD8 AUROC = 0.821, 95% CI = 0.664-0.977).Conclusions: Both IQCODE-SF and AD8 are valid measures of pre-stroke dementia. Higher cut points for AD8 may improve performance in the acute stroke setting. Based on consistent superiority across a range of validity analyses, IQCODE-SF may be preferable to AD8 for pre-stroke dementia screening. [ABSTRACT FROM AUTHOR]

The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu&FK@RNPs), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain. Meanwhile, these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS. As a result, the cognition of AD mice was significantly improved and the quantity of A β plaques was decreased. Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons. Besides, the neuroinflammation dominated by NF- κ B pathway was significantly inhibited with decreased NF- κ B and IL-1 β in the brain. Overall, Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion. Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection. Reactive oxygen species (ROS)-responsive programmed receptor of advanced glycation endproducts (RAGE) targeted delivery depot of Ibu&FK@RNPs was prepared to act on astrocytes and neurons in the treatment of Alzheimer's disease (AD) through anti-neuroinflammation and neuroprotection. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a common neurovascular disorder disease often characterized by episodic headaches that can develop chronic disorders. Acupuncture as a non-pharmacological therapy has been extensively used to manage migraine prevention and treatment in clinical practice. Many studies focused on acupuncture therapy for migraine, but none analyzed the publications quantitatively and qualitatively. The aim of this study is to show the recent researches and trend of advances in this field based on quantitative and qualitative analyses. Methods: Publications related to acupuncture research about migraine were retrieved from the Web of Science (WoS) Core Collection and Scopus database. The quantitative data analysis was performed to show the recent researches and trend of advances from six perspectives: annual scientific production, countries, institutions, authors, journals, and keywords. For the qualitative analysis, acupuncture research about migraine was analyzed from the top twenty most highly cited articles. Results: The number of annual scientific production steadily increased with some fluctuations over the years. The country and institutions contributing most to this field are China and Chengdu University of Traditional Chinese Medicine. Zhao Ling was the most relevant author in this field, Linde Klaus was the highly co-cited author. The leading journal regarding the number of selected articles was "Zhongguo Zhen Jiu". The top twenty most highly cited articles were divided into two categories: original articles and reviews. Among these two categories, original articles occupied the vast majority. Moreover, the real effectiveness of acupuncture for migraine prevention and treatment was the research frontier and hot spot. Conclusion: Results of our analysis indicate that the number of publications showed an overall increasing trend, demonstrating that this research field still has a promising future. In addition, more researchers will probably focus their work on the difference between verum acupuncture and usual care for preventing and treating migraine. [ABSTRACT FROM AUTHOR]

Neurological/neurovascular disorders constitute the leading cause of disability and the second leading cause of death globally. Major neurological/neurovascular disorders or diseases include cerebral stroke, Alzheimer's disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, and others. Their pathophysiology is considered highly complex and is the main obstacle in developing any drugs for these diseases. In this review, we have described the endothelin system, its involvement in neurovascular disorders, the importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN—sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders/diseases. In addition, we have highlighted the results of our preclinical and clinical studies related to these diseases. The phase I safety and tolerability study of sovateltide has shown it as a safe and tolerable compound at therapeutic dosages. Furthermore, preclinical and clinical phase II studies have demonstrated the efficacy of sovateltide in treating acute ischemic stroke. It is under development as a first-in-class drug. In addition, efficacy studies in Alzheimer's disease (AD), acute spinal cord injury, and neonatal hypoxic-ischemic encephalopathy (HIE) are ongoing. Successful completion of these studies will validate that ETBRs signaling can be an important target in developing drugs to treat neurological/neurovascular diseases. [ABSTRACT FROM AUTHOR]

The brain and spinal cord are immune-privileged organs, but in the disease state protection mechanisms such as the blood brain barrier (BBB) are ineffective or overcome by pathological processes. In neuroinflammatory diseases, microglia cells and other resident immune cells contribute to local vascular inflammation and potentially a systemic inflammatory response taking place in parallel. Microglia cells interact with other cells impacting on the integrity of the BBB and propagate the inflammatory response through the release of inflammatory signals. Here, we discuss the activation and response mechanisms of innate and adaptive immune processes in response to neuroinflammation. Furthermore, the clinical importance of neuroinflammatory mediators and a potential translational relevance of involved mechanisms are addressed also with focus on non-classical immune cells including microglia cells or platelets. As illustrative examples, novel agents such as Anfibatide or Revacept, which result in reduced recruitment and activation of platelets, a subsequently blunted activation of the coagulation cascade and further inflammatory process, demonstrating that mechanisms of neuroinflammation and thrombosis are interconnected and should be further subject to in depth clinical and basic research. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that functional Near-Infrared Spectroscopy (fNIRS) can provide an essential bridge between our current understanding of neural circuit organization and cortical activity in the developing brain. Indeed, fNIRS allows studying brain functions through the measurement of neurovascular coupling that links neural activity to subsequent changes in cerebral blood flow and hemoglobin oxygenation levels. While the literature offers a multitude of fNIRS applications to typical development, only recently this tool has been extended to the study of neurodevelopmental disorders (NDDs). The exponential rise of scientific publications on this topic during the last years reflects the interest to identify a "fNIRS signature" as a biomarker of high translational value to support both early clinical diagnosis and treatment outcome. The purpose of this systematic review is to describe the updating clinical applications of fNIRS in NDDs, with a specific focus on preschool population. Starting from this rationale, a systematic search was conducted for relevant studies in different scientific databases (Pubmed, Scopus, and Web of Science) resulting in 13 published articles. In these studies, fNIRS was applied in individuals with Autism Spectrum Disorder (ASD) or infants at high risk of developing ASD. Both functional connectivity in resting-state conditions and task-evoked brain activation using multiple experimental paradigms were used in the selected investigations, suggesting that fNIRS might be considered a promising method for identifying early quantitative biomarkers in the autism field. [ABSTRACT FROM AUTHOR]

Mutations in the ATP‐binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes, and blood vessels and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history. [ABSTRACT FROM AUTHOR]

The neurovascular unit (NVU) is a highly organized multicellular system localized in the brain, formed by neuronal, glial (astrocytes, oligodendrocytes, and microglia) and vascular (endothelial cells and pericytes) cells. The blood–brain barrier, a complex and dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma, is a component of the NVU. In a variety of neurological disorders, including Alzheimer's disease, multiple sclerosis, and stroke, dysfunctions of the NVU occurs. There is, however, a lack of knowledge regarding the NVU function in leukodystrophies, which are rare monogenic disorders that primarily affect the white matter. Since leukodystrophies are rare diseases, human brain tissue availability is scarce and representative animal models that significantly recapitulate the disease are difficult to develop. The introduction of human induced pluripotent stem cells (hiPSC) now makes it possible to surpass these limitations while maintaining the ability to work in a biologically relevant human context and safeguarding the genetic background of the patient. This review aims to provide further insights into the NVU functioning in leukodystrophies, with a special focus on iPSC-derived models that can be used to dissect neurovascular pathophysiology in these diseases. [ABSTRACT FROM AUTHOR]