Brain Blood Vessels Research Articles

Telomere length as a biomarker for cerebrovascular diseases: current evidence.

Cerebrovascular disease (CVD) includes a range of conditions affecting the brain's blood vessels, which can result in reduced blood flow to brain tissue. The most common manifestation of CVD is stroke, the second leading cause of death and the third leading cause of disability worldwide. Major risk factors for CVD encompass gender, age, smoking, hypertension, diabetes, physical inactivity, obesity, alcohol consumption, and metabolic syndrome. Research suggests a link between telomere length and an increased risk of CVD, particularly in ischemic stroke cases. This review highlights key findings on the relationship between telomere length and CVD, underscoring its clinical importance. The analysis utilizes scientific literature from PubMed, Scopus, and SciELO up to 2024. Results show that shorter telomere length is associated with various types of CVD, including stroke, ischemic stroke, hemorrhagic stroke, and cardioembolic stroke. Some studies propose that telomere length measurement could be a valuable biomarker for CVD, potentially improving prevention, diagnosis, and management strategies.

Head-up Surgery in Current Neurosurgery with Neuroendoscope and Exoscope

Neurological surgery requires techniques and equipment to magnify the delicate brain structures and blood vessels that are difficult to discern with the naked eye. The introduction of surgical microscopes in the 1960s marked a breakthrough leading to the development of microsurgery and significant improvements in the safety and efficacy of neurosurgery. Subsequently, minimally invasive neurosurgery became prevalent, particularly with advancements in endoscopic technology in the 1990s. Initially met with skepticism, neuroendoscopy progressed alongside device development, gaining consensus on its utility. In the 2010s, exoscope technology emerged, offering high-definition 3D visualization, and reducing surgeon and patient restrictions compared to traditional microscopes. Heads-up neurosurgery involves projecting the surgical field onto a monitor using a neuroendoscope and an exoscope, allowing the surgeon to perform the operation while looking at the front monitor with the head raised in a relaxed, natural posture. Heads-up surgery using neuroendoscopy and an exoscope offers many advantages over traditional microscopic surgery and is expected to enhance surgical outcomes through the integration of these advanced technologies, potentially becoming a significant breakthrough in neurosurgery. This article provides an overview of the latest heads-up procedures that utilize neuroendoscopy and exoscopy. (Received May 2, 2024; Accepted June 21, 2024; Published November 1, 2024).

Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations.

Capillary malformations (CM) are congenital vascular irregularities of capillary and venous blood vessels that appear in the skin, leptomeninges of the brain, and the choroid of the eye in the disorder known as Sturge Weber Syndrome (SWS). More common are non-syndromic CM found only in the skin, without brain or ocular involvement. A somatic activating mutation in GNAQ (p.R183Q) is found in ~ 90% of syndromic and non-syndromic CM specimens and is present in CD31pos endothelial cells isolated from brain and skin CM specimens. Endothelial expression of the GNAQ p.R183Q variant is sufficient to form CM-like vessels in mice. Given the distinct features and functions of blood vessels in the brain versus the skin, we examined the features of CM vessels in both tissues to gain insights into the pathogenesis of CM. Herein, we present morphologic characteristics of CM observed in specimens from brain and skin. The GNAQ p.R183Q variant allelic frequency in each specimen was determined by droplet digital PCR. Sections were stained for endothelial cells, tight junctions, mural cells, and macrophages to assess the endothelium as well as perivascular constituents. CM blood vessels in brain and skin were enlarged, exhibited fibrin leakage and reduced zona occludin-1 and claudin-5, and were surrounded by MRC1pos/LYVE1pos macrophages. In contrast, the CMs from brain and skin differ in endothelial sprouting activity and localization of mural cells. These characteristics might be helpful in the development of targeted and/or tissue specific therapies to prevent or reverse non-syndromic and syndromic CM.

Chronic Stress Exacerbates Cerebral Amyloid Angiopathy Through Promoting Neutrophil Extracellular Traps Formation.

Cerebral amyloid angiopathy (CAA) is the leading cause of vascular dementia among the elderly. Neuropsychiatric symptoms are commonly manifested in cerebral amyloid angiopathy patients but are usually considered as consequences of cerebral amyloid angiopathy pathology. Here, it is reported that chronic stress promotes cerebral amyloid angiopathy progression, which enhances deposition of amyloid protein beta (Aβ) in brain blood vessels and exacerbates subsequent brain injury. Mechanistically, neutrophil is implicated in cerebral amyloid angiopathy development. Aβ that accumulates in brain vasculature induces neutrophil extracellular traps (NETs) by activating STAT6 signaling, which inhibits neutrophil apoptosis and switches the programmed cell death toward NETosis. During chronic stress, circulatory Norepinephrine (NE) strengthens STAT6 activation in neutrophil and promotes NET formation, thus exacerbates the NET-dependent angiopathy. It is demonstrated that inhibiting neutrophil chemotaxis towards brain or suppressing NET formation both ameliorate cerebral amyloid angiopathy severity in the context of chronic stress. Therefore, it is proposed that stress-associated psychological disorders and NETs are promising therapeutic targets in cerebral amyloid angiopathy.

Expression of Manganese Transporters ZIP8, ZIP14, and ZnT10 in Brain Barrier Tissues.

Manganese (Mn) is an essential trace mineral for brain function, but excessive accumulation can cause irreversible nervous system damage, highlighting the need for proper Mn balance. ZIP14, ZnT10, and ZIP8 are key transporters involved in maintaining Mn homeostasis, particularly in the absorption and excretion of Mn in the intestine and liver. However, their roles in the brain are less understood. The blood-cerebrospinal fluid barrier and the blood-brain barrier, formed by the choroid plexus and brain blood vessels, respectively, are critical for brain protection and brain metal homeostasis. This study identified ZIP14 on the choroid plexus epithelium, and ZIP8 and ZnT10 in brain microvascular tissue. We show that despite significant Mn accumulation in the CSF of Znt10 knockout mice, ZIP14 expression levels in the blood-cerebrospinal fluid barrier remain unchanged, indicating that ZIP14 does not have a compensatory mechanism for regulating Mn uptake in the brain in vivo. Additionally, Mn still enters the CSF without ZIP14 when systemic levels rise. This indicates that alternative transport mechanisms or compensatory pathways ensure Mn balance in the CSF, shedding light on potential strategies for managing Mn-related disorders.

HUBUNGAN ANTARA PENGETAHUAN KELUARGA DAN DUKUNGAN KELUARGA DENGAN KEJADIAN STROKE PADA LANSIA

ABSTRACT Stroke is a cerebrovascular disease (brain blood vessels) which is characterized by impaired brain function due to damage or death of brain tissue due to reduced or blocked blood and oxygen flow to the brain. Objective: to determine the relationship between family knowledge and family support and the incidence of stroke in the elderly. This type of research uses an analytical survey method with a cross sectional approach. The sample in From the results of the analysis it was found that there was a significant relationship between this study amounting to 36 people using accidental sampling technique. From the results of the analysis it was found that there was a significant relationship between Family Knowledge (ρ-value=0.031), and family support (ρ-value=0.040), and the incidence of stroke in the elderly. Suggestion: provide health education for families regarding stroke, treatment, rehabilitation and care of stroke patients at home. Nurses are also expected to be able to help patients and families in increasing the patient's motivation to recover.

Imaging arterial and venous vessels using Iron Dextran enhanced multi-echo 3D gradient echo MRI at 7T.

Iron Dextran is a widely used iron oxide compound to treat iron-deficiency anemia patients in the clinic. Similar to other iron oxide compounds such as Ferumoxytol, it can also be used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent due to its strong iron-induced T2 and T2* shortening effects. In this study, we seek to evaluate the feasibility of using Iron Dextran enhanced multi-echo susceptibility weighted imaging (SWI) MRI at 7T to image arterial and venous blood vessels in the human brain. Phantom experiments were performed to measure the r2* relaxivity for Iron Dextran in blood, based on which the SWI sequence was optimized. Pre- and post-infusion MR images were acquired in human subjects from which maps of arteries and veins were extracted. The post-contrast SWI images showed enhanced susceptibility difference between blood and the surrounding tissue in both arteries and veins. Our results showed that the proposed Iron Dextran enhanced multi-echo SWI approach allowed the visualization of blood vessels with diameters down to ~100 μm, including small blood vessels supplying and draining small brain structures such as the hippocampus. We conclude that Iron Dextran can be an alternative iron-based MRI contrast agent for blood vessel imaging in the human brain.

Inter-subject cerebrovascular variability: a source of uncertainty for dose calculation to circulating blood cells for glioblastoma patients treated with modern radiotherapy techniques

Purpose. To assess how inter-subject variations in brain vasculature among glioblastoma (GBM) patients affects the calculated dose received by circulating blood cells (CBC) during radiotherapy and its subsequent impact on CBC depletion. Methods. Ten GBM patients treated with either intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) were selected. For each patient, 23 cerebrovascular models were developed based on 23 healthy subject MR-angiography data to simulate intra- and inter-subject blood vessel diversity. Based on the corresponding treatment plan of the patient, the dose to CBC was calculated for all the 230 scenarios. The impact of inter-subject variation on fraction of irradiated blood volume (VD >0 cGy) and lymphocyte kill rates as a function of the clinical target volume (CTV) size and treatment technique were analyzed. Results. The dose fluctuation to CBC was higher in IMRT plans compared to VMAT plans. The uncertainty in the VD >0 cGy was 18.3% for IMRT and 2.0% (CI95%) for VMAT and the dispersion of the D 2% index was 6 cGy for IMRT and 1 cGy for VMAT (CI95%) for one single treatment fraction of 200 cGy. The uncertainty in killed CBC due to inter-subject diversity in brain blood vessel increased with increasing CTV size and was σ = 11.2%. Conclusions. VMAT showed greater robustness against inter-subject variation in blood vessels compared to IMRT. We recommend considering the uncertainty in depleting CBC resulting from the use of less patient-specific and generic blood vessel phantoms to improve the radiation-induced lymphopenia assessments.

Lecanemab and Vascular-Amyloid Deposition in Brains of People With Down Syndrome

Anti-β-amyloid immunotherapy using lecanemab is becoming increasingly available to patients with Alzheimer disease (AD). Individuals with Down syndrome (DS) develop AD neuropathology by age 40 years, representing a significant cohort of genetically determined AD. To investigate the binding properties of lecanemab in the brains of people with DS, in anticipation of their inclusion in clinical trials or access to antiamyloid immunotherapies. The study included cases of postmortem brain tissue analysis from 15 individuals with DS aged 43 to 68 years that were acquired from Alzheimer Disease research centers at the University of California, Irvine and the University of Kentucky from 2008 to 2021. Data were analyzed from August 2023 through May 2024. The binding properties of lecanemab were assessed in brain tissue. The primary outcome was the extent of lecanemab binding to amyloid plaques and brain blood vessels. Tissue from 15 people (8 were female [53%]) with DS ranging in age from 43 to 68 (mean, 56.6) years were included in the study. Lecanemab-labeled amyloid plaques appeared in all 15 DS cases studied, indicating potential target engagement. However, extensive binding of lecanemab to brain blood vessels in DS was observed, raising significant safety concerns. These findings underscore the necessity for clinical trials of lecanemab in people with DS to evaluate both safety and efficacy, particularly in individuals older than 43 years. These findings suggest significant binding of lecanemab to cerebral amyloid angiopathy in DS. Lecanemab should be rigorously tested in clinical trials for AD in the DS population to determine its safety and efficacy, especially in those older than 43 years.

The Relationship Between Self-Concept and Post-Stroke Depression in Stroke Patients

Stroke is when something goes wrong with the blood vessels in your brain, and it can cause serious problems like not being able to move or talk. The are two main types of strokes – one where the blood vessels get blocked (called ischemic) and another where they burst (called hemorrhagic). The blocked kind is more common and happens most often (almost 90% of strokes are ischemic). Meanwhile, hemorrhagic stroke is caused by a leak or rupture of blood vessels in or around the brain, thereby blocking blood flow to brain tissue. Based on preliminary studies, it was found that there was still a high incidence of depression in post-stroke patients at RSU ANNA Medika Madura. The research aims to determine whether there is a relationship between self-concept and post-stroke depression in stroke patients. This research method uses cross-sectional. The independent variable is self-concept, while the dependent variable is post-stroke depression. The total population was 94 stroke patients with a sample of 76 respondents. The sampling technique uses purposive sampling. The instruments used were self-concept questionnaires and HDRS. The statistical test uses the Spearman rank correlation test with a 0.05. The results of the Spearman rank test for the self-concept variable with post-stroke depression obtained a p-value of 0.000 < α 0.05. This research concludes that there is a relationship between self-concept and post-stroke depression in stroke patients. It is hoped that the researchers' suggestions can increase understanding about stroke, improve self-concept to avoid depression.

Cerebrovascular Endothelial Dysfunction: Role of BACE1.

Dysfunctional endothelium is increasingly recognized as a mechanistic link between cardiovascular risk factors and dementia, including Alzheimer disease. BACE1 (β-site amyloid-β precursor protein-cleaving enzyme 1) is responsible for β-processing of APP (amyloid-β precursor protein), the first step in the production of Aβ (amyloid-β) peptides, major culprits in the pathogenesis of Alzheimer disease. Under pathological conditions, excessive activation of BACE1 exerts detrimental effects on endothelial function by Aβ-dependent and Aβ-independent mechanisms. High local concentration of Aβ in the brain blood vessels is responsible for the loss of key vascular protective functions of endothelial cells. More recent studies recognized significant contribution of Aβ-independent proteolytic activity of endothelial BACE1 to the pathogenesis of endothelial dysfunction. This review critically evaluates existing evidence supporting the concept that excessive activation of BACE1 expressed in the cerebrovascular endothelium impairs key homeostatic functions of the brain blood vessels. This concept has important therapeutic implications. Indeed, improved understanding of the mechanisms of endothelial dysfunction may help in efforts to develop new approaches to the protection and preservation of healthy cerebrovascular function.

Intracranial vasculopathy: an important organ damage in young adult patients with late-onset Pompe disease

BackgroundLate-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients.ResultsNeuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging.ConclusionsIntracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.

A bright Ce-based downshifting luminescence nanoprobe for NIR-IIb vessel imaging

Nanomaterials with unique emission in the second near-infrared window (NIR-II, 1000–1700 nm) are regarded as the promising probes for visualization of tumor vessels and cerebrovascular architecture, because of their superior features such as deep tissue penetration and large imaging resolution. Herein, the new Ce-based fluoride nanoparticles (NPs) with high-efficiency NIR-IIb emission were explored for high-resolution vascular imaging and tumor associated vessel detection. Under the same synthesis conditions, the Ce-based fluoride present the preferential formation CeF3 host and low upconversion (UC) emission, but possess more strong (1.45 times) NIR-IIb downconversion (DC) emission centered at 1525 nm under the irradiation of a 980 nm laser, which is significantly different from the traditional NaYF4:Yb/Er host. Through the efficient cross relaxation between Ce3+ and Er3+, intense NIR-IIb luminescence from Er3+ with high quantum yields were achieved, which make sure the entire mouse body and brain blood vessel imaging with supernal resolution (47.6 μm) were demonstrated. Moreover, the optical imaging in NIR-IIb region guided tumorous vascular visualization was successfully achieved. Therefore, the explored CeF3 NPs with boosting NIR-IIb emission can be employed as new diagnostic bio-probes used in high spatial resolution tumorous vessel detection.

Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations.

Capillary malformations (CM) are congenital vascular irregularities of capillary and venous blood vessels that appear in the skin, leptomeninges of the brain, and the choroid of the eye in the disorder known as Sturge Weber Syndrome (SWS). More common are non-syndromic CM found only in the skin, without brain or ocular involvement. A somatic activating mutation in GNAQ (p.R183Q) is found in ~90% of syndromic and non-syndromic CM specimens and is present in CD31pos endothelial cells isolated from brain and skin CM specimens. Endothelial expression of the GNAQ p.R183Q variant is sufficient to form CM-like vessels in mice. Given the distinct features and functions of blood vessels in the brain versus the skin, we examined the features of CM vessels in both tissues to gain insights into the pathogenesis of CM. Herein, we present morphologic characteristics of CM observed in specimen from brain and skin. The GNAQ p.R183Q variant allelic frequency in each specimen was determined by droplet digital PCR. Sections were stained for endothelial cells, tight junctions, mural cells, and macrophages to assess the endothelium as well as perivascular constituents. CM blood vessels in brain and skin were enlarged, exhibited fibrin leakage and reduced zona occludin-1, and were surrounded by MRC1pos/LYVE1pos macrophages. In contrast, the CMs from brain and skin differ in endothelial sprouting activity and localization of mural cells. These characteristics might be helpful in the development of targeted and/or tissue specific therapies to prevent or reverse non-syndromic and syndromic CM.

Brain Blood Vessel Segmentation based on Region Growing and U-net Neural Network

Aiming at the problems of insufficient feature extraction in existing deep learning-based cerebrovascular segmentation methods and uneven segmentation results when the original imaging quality is poor, a cerebrovascular segmentation method that integrates region growing and an improved U-net neural network is proposed. Based on the deep learning segmentation results, automatic seed point selection for region growing is performed and fused to improve the segmentation accuracy at the pixel level. In this work, the integrated segmentation method improves the Dice coefficient from 0.805 to 0.878 and the Average Hausdorff Distance (AHD) from 3.949 to 0.903 compared to the deep learning segmentation method.

Recent Research Progress on the Use of Transcranial Magnetic Stimulation in the Treatment of Vascular Cognitive Impairment.

Vascular Cognitive Impairment (VCI) is a condition where problems with brain blood vessels lead to a decline in cognitive abilities, commonly affecting the elderly and placing a significant burden on both patients and their families. Compared to medication and surgery, Transcranial Magnetic Stimulation (TMS) is a non-invasive treatment option with fewer risks and side effects, making it particularly suitable for elderly patients. TMS not only assesses the excitability and plasticity of the cerebral cortex, but its effectiveness in treating Vascular Cognitive Impairment (VCI) and its subtypes has also been validated in numerous clinical trials worldwide. However, there is still a lack of review on the physiological mechanisms of TMS treatment for VCI and its specific clinical application parameters. Therefore, this article initially provided a brief overview of the risk factors, pathological mechanisms, and classification of VCI. Next, the article explained the potential physiological mechanisms of TMS in treating VCI, particularly its role in promoting synaptic plasticity, regulating neurotransmitter balance, and improving the function of the default mode network. Additionally, The article also summarizes the application of rTMS in treating VCI and its subtypes, VCI-related sleep disorders, and the use of TMS in follow-up studies of VCI patients, providing empirical evidence for the clinical application of TMS and rTMS technologies.

In-Brain Multiphoton Imaging of Vaterite Cargoes Loaded with Carbon Dots.

Biocompatible fluorescent agents are key contributors to the theranostic paradigm by enabling real-time in vivo imaging. This study explores the optical properties of phenylenediamine carbon dots (CDs) and demonstrates their potential for fluorescence imaging in cells and brain blood vessels. The nonlinear absorption cross-section of the CDs was measured and achieved values near 50 Goeppert-Mayer (GM) units with efficient excitation in the 775-895 nm spectral range. Mesoporous vaterite nanoparticles were loaded with CDs to examine the possibility of a biocompatible imaging platform. Efficient one- and two-photon imaging of the CD-vaterite composites uptaken by diverse cells was demonstrated. For an in vivo scenario, CD-vaterite composites were injected into the bloodstream of a mouse, and their flow was monitored within the blood vessels of the brain through a cranial window. These results show the potential of the platform for high-brightness biocompatible imaging with the potential for both sensing and simultaneous drug delivery.

#850 The association between proteinuria and stroke: results from the non-communicable diseases screening programme of Chiang Mai Region, Northern Thailand

Abstract Background and Aims Stroke is a significant global health issue, representing the second leading cause of death and a major contributor to disability. It can be classified into two main types: ischemic stroke, caused by blockage of a brain blood vessel, and haemorrhagic stroke, resulting from blood vessel rupture. Chronic kidney disease (CKD) is another prevalent health concern, affecting approximately 10% of all populations worldwide. CKD impairs kidney function and has been associated with an increased risk of cerebrovascular events, including stroke. Within the Northern Thai population, the prevalence of CKD is higher than the global average, underscoring the importance of investigating the relationship between CKD and stroke in this region. Method All patients for which accurate proteinuria measurement was obtained as part of the NCD screening program in Chiang Mai, Northern Thailand were included in the study. Multilinear cox regression analysis was used to estimate the hazards ratio for the association between proteinuria on stroke. The model was adjusted for other significant confounders of the association including age, sex, CKD, diabetes, hypertension and hypercholesterolaemia Results In a cohort of 3967 patients for which accurate proteinuria measurements were obtained and for whom had complete data for covariates, there was no evidence for an association between proteinuria and stroke. Hazards ratio for stroke in patients with trace proteinuria (adjusted for covariates) was 1.08 (95% CI 0.80-1.45) and positive proteinuria 0.06 (0.78-1.44) compared to a baseline of no proteinuria. Conclusion This study provides important insights into stroke risk factors in the Northern Thai population. The lack of substantial association between proteinuria and stroke suggests that proteinuria may not independently contribute to stroke risk in this cohort. Generalizability, however, is limited due to overrepresentation of diabetes and hypercholesterolaemia in the cohort, which is a strong independent risk factor for stroke. Increasing age is identified as the most critical risk factor for stroke. Understanding these associations can guide targeted interventions and public health strategies for stroke prevention in this population. The study limitations highlight the importance of analysis of a cohort that is more representative of a wider population in terms of chronic disease, such as diabetes and hypercholesterolaemia, and highlights the importance of longer follow up to fully elucidate whether proteinuria has an association with stroke. Furthermore the study raises questions as to whether measurement of proteinuria via urine dipstick analysis may limit conclusions that can be drawn compared to more robust methods such as urine albumin:creatinine or urine protein:creatinine ratios. Finally this study may be underpowered to detect subtle changes of a hazards ratio of less than 1.2, so is at risk of a type 2 statistical error.

EEG biomarkers analysis in different cognitive impairment after stroke: an exploration study.

Stroke is a cerebrovascular illness that brings about the demise of brain tissue. It is the third most prevalent cause of mortality worldwide and a significant contributor to physical impairment. Generally, stroke is triggered by blood clots obstructing the brain's blood vessels, or when these vessels rupture. And, the cognitive impairment's evaluation and detection after stroke is crucial research issue and significant project. Thus, the objective of this work is to explore an potential neuroimage tool and find their EEG biomarkers to evaluate and detect four cognitive impairment levels after stroke. In this study, power density spectrum (PSD), functional connectivity map, and one-way ANOVA methods were proposed to analyze the EEG biomarker differences, and the number of patient participants were thirty-two human including eight healthy control, mild, moderate, severe cognitive impairment levels, respectively. Finally, healthy control has significant PSD differences compared to mid, moderate and server cognitive impairment groups. And, the theta and alpha bands of severe cognitive impairment groups have presented consistent superior PSD power at the right frontal cortex, and the theta and beta bands of mild, moderated cognitive impairment (MoCI) groups have shown significant similar superior PSD power tendency at the parietal cortex. The significant gamma PSD power difference has presented at the left-frontal cortex in the mild cognitive impairment (MCI) groups, and severe cognitive impairment (SeCI) group has shown the significant PSD power at the gamma band of parietal cortex. At the point of functional connectivity map, the SeCI group appears to have stronger functional connectivity compared to the other groups. In conclusion, EEG biomarkers can be applied to classify different cognitive impairment groups after stroke. These findings provide a new approach for early detection and diagnosis of cognitive impairment after stroke and also for the development of new treatment options.

The role of CCN1 in kidney-brain crosstalk

Cognitive impairment and dementia are major global health problems of the aging human population. It is estimated that about 55 million people were living with dementia in 2019 and this number is expected to triple by 2050. Dementia can result from abnormal structure and function of brain blood vessels that may develop in a variety of conditions including chronic kidney disease (CKD). Recent studies from our laboratory suggest that in addition to controlling blood volume and blood pressure (renin), and blood cell count (erythropoietin), the kidney produces novel systemic angiogenic hormones to maintain blood vessels, such as the matricellular protein Cellular Communication Network factor 1 (CCN1). These hormones are then released to the blood and may act as new molecular mechanisms of kidney-brain crosstalk. We hypothesized that kidney-derived CCN1 helps to preserve the normal structure and function of blood vessels throughout the body, including a healthy blood-brain barrier (BBB). We further hypothesized that reduced plasma CCN1 caused by diminished renal production of CCN1 due to kidney disease plays a major role in the development of brain vascular dysfunction, and therefore in the pathogenesis and progression of dementia and cognitive impairment. Intravital multiphoton (MPM) imaging of the intact mouse brain in control or after 5/6 nephrectomy (5/6 Nx), a well-established mouse model of chronic kidney disease (CKD) was used to measure changes in BBB permeability with or without chronic CCN1 treatment. Kidney and BBB structure/function phenotyping was performed using CCN1 ELISA assay, the Medibeacon transdermal GFR measurement system, tissue harvest, and immunohistochemistry. Compared to control, 5/6 Nx mice had reduced plasma CCN1 levels, reduced GFR, but no difference in systolic blood pressure. MPM imaging showed increased fluorescence intensity of mid-size plasma proteins (A680 conjugated Albumin 70 kDa) compared to high molecular weight markers (A488 conjugated Dextran 500 kDa) in brain interstitium in 5/6 Nx compared to control. In addition, the density of cell-to-cell junctions in brain endothelial cells were 20% reduced in CKD compared to control healthy mice. In brain endothelial cells cultured in vitro, CCN1 treatment had protective effects on cell proliferation, motility and angiogenesis as confirmed by scratch and tube formation assays. In summary, this study identified new mechanisms of kidney-brain crosstalk, and helped to improve our mechanistic understanding of cerebrovascular pathology in CKD. DK123564, DK064324, DK135290. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.