Brain Vessels Research Articles

DRG2 Depletion Promotes Endothelial Cell Senescence and Vascular Endothelial Dysfunction.

Endothelial cell senescence is involved in endothelial dysfunction and vascular diseases. However, the detailed mechanisms of endothelial senescence are not fully understood. Here, we demonstrated that deficiency of developmentally regulated GTP-binding protein 2 (DRG2) induces senescence and dysfunction of endothelial cells. DRG2 knockout (KO) mice displayed reduced cerebral blood flow in the brain and lung blood vessel density. We also determined, by Matrigel plug assay, aorta ring assay, and in vitro tubule formation of primary lung endothelial cells, that deficiency in DRG2 reduced the angiogenic capability of endothelial cells. Endothelial cells from DRG2 KO mice showed a senescence phenotype with decreased cell growth and enhanced levels of p21 and phosphorylated p53, γH2AX, senescence-associated β-galactosidase (SA-β-gal) activity, and senescence-associated secretory phenotype (SASP) cytokines. DRG2 deficiency in endothelial cells upregulated arginase 2 (Arg2) and generation of reactive oxygen species. Induction of SA-β-gal activity was prevented by the antioxidant N-acetyl cysteine in endothelial cells from DRG2 KO mice. In conclusion, our results suggest that DRG2 is a key regulator of endothelial senescence, and its downregulation is probably involved in vascular dysfunction and diseases.

Chemical fluorescence-based dye staining for 3-dimensional histopathology analysis

ABSTRACT Tissue clearing for 3-dimensional (3D) imaging is increasingly utilized in many biomedical applications, including the pathological examination of human biopsy specimens. Although many protocols offer rapid and efficient tissue clearing (>1 d), immunofluorescence labeling of thick specimens is a highly time-consuming process. The use of low molecular weight chemical dyes has potential benefits in terms of speed and quality of 3D labeling. Accordingly, we tested several chemical dyes to assess their potential applications in 3D imaging. The combination of SYTO 16 and eosin (S&E) was found to be a potential fluorescent version of the hematoxylin–eosin (H&E) stain. Furthermore, picrosirius red (for collagen), Congo red (for senile plaques), and fluorescent Nissl (for neurons in the normal brain or blood vessels in the injured brain) stains can be used alone or in combination with antibody labeling. As chemical labeling requires a relatively short incubation time (<1 d), fluorescent chemical dyes could expedite the 3D imaging process.

The Interplay Between Brain Vascular Calcification and Microglia.

Vascular calcifications are characterized by the ectopic deposition of calcium and phosphate in the vascular lumen or wall. They are a common finding in computed tomography scans or during autopsy and are often directly related to a pathological condition. While the pathogenesis and functional consequences of vascular calcifications have been intensively studied in some peripheral organs, vascular calcification, and its pathogenesis in the central nervous system is poorly characterized and understood. Here, we review the occurrence of vessel calcifications in the brain in the context of aging and various brain diseases. We discuss the pathomechanism of brain vascular calcification in primary familial brain calcification as an example of brain vessel calcification. A particular focus is the response of microglia to the vessel calcification in the brain and their role in the clearance of calcifications.

513 Surveilling Cerebrospinal Fluid Protein Biomarkers in Brain Metastasis

INTRODUCTION: Cerebrospinal fluid (CSF) is in constant and direct contact with the brain parenchyma, vessels and meninges. The distribution and relative isolation of CSF makes it valuable in the evaluation of central nervous system pathologies. CSF protein profiling has been widely studied in neuro-degenerative and inflammatory diseases. This analysis may also be relevant in patients with brain metastases. METHODS: Patients were enrolled between May 2017 and March 2020 under an IRB protocol. CSF and plasma were processed and stored at -80°C. Concentrations of 142 soluble proteins were quantified by Luminex (Eve Technologies). RESULTS: Seventy-four patients were included in this study. Of the 60 patients with brain metastases, most had lung cancer (N=29), melanoma (N=10) and breast cancer (N=7). Non-malignant samples included normal pressure hydrocephalus (NPH, N=5), CSF leak (N=9) and radiation necrosis (N=9). Of the 142 soluble proteins profiled, 44 were significantly elevated in patients with LMD compared to intraparenchymal disease. None were more elevated in intraparenchymal disease. This finding was not replicated in the plasma. The CSF profile of patients with LMD and NPH were highly similar. CONCLUSION: Soluble CSF proteins are detectable in patients with brain metastases and concentrations differ based on extent of intracranial disease. This difference was not seen in plasma. These findings suggest that patients with LMD have a protein signature, different from those with intraparenchymal brain metastases only, which can help augment current diagnostic standards and reflect the tumor microenvironment. The similarity of LMD and NPH CSF proposes a similar pathogenesis and warrants further exploration. Further analysis of clinical data including survival and treatment response may assist in the management of patients with brain metastases.

A Current Review of Systemic Lupus Erythematosus Treatment Using Monoclonal Antibodies

Abstract: Lupus is a heterogeneous and inflammatory autoimmune disease that affects the immune system of the body. This disease affects multiple tissues and organs. The most frequent kind of lupus is systemic lupus erythematosus (SLE). SLE is an autoimmune illness in which the immune system targets the body's tissues, resulting in extensive inflammation and tissue destruction in the organs involved. Joints, skin, brain, lungs, kidneys, and blood vessels can all be affected. It appears to be a form of B-cell disease in which autoantibodies attack the cells. Systemic lupus erythematosus autoimmune diseases involve different treatment methods. These abnormalities are due to the presence of autoantibodies, and these contribute to the degeneration of the body’s immune system. In this review, we will focus on various therapies, including SLE treatments, such as B-cell therapy, cytokine therapy, interferon targets, and anticomplementary therapies, all of which have become challenging. We will also discuss post-marketing use and ongoing clinical trials, as well as safety and effective doses.

Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit.

The neurovascular unit (NVU) is a conceptual framework that has been proposed to better explain the relationships between the neural cells and blood vessels in the human brain, focused mainly on the brain gray matter. The major components of the NVU are the neurons, astrocytes (astroglia), microvessels, pericytes, and microglia. In addition, we believe that oligodendrocytes should also be included as an indispensable component of the NVU in the white matter. Of all these components, astrocytes in particular have attracted the interest of researchers because of their unique anatomical location; these cells are interposed between the neurons and the microvessels of the brain. Their location suggests that astrocytes might regulate the cerebral blood flow (CBF) in response to neuronal activity, so as to ensure an adequate supply of glucose and oxygen to meet the metabolic demands of the neurons. In fact, the adult human brain, which accounts for only 2% of the entire body weight, consumes approximately 20–25% of the total amount of glucose and oxygen consumed by the whole body. The brain needs a continuous supply of these essential energy sources through the CBF, because there are practically no stores of glucose or oxygen in the brain; both acute and chronic cessation of CBF can adversely affect brain functions. In addition, another important putative function of the NVU is the elimination of heat and waste materials produced by neuronal activity. Recent evidence suggests that astrocytes play pivotal roles not only in supplying glucose, but also fatty acids and amino acids to neurons. Loss of astrocytic support can be expected to lead to malfunction of the NVU as a whole, which underlies numerous neurological disorders. In this review, we shall focus on historical and recent findings with regard to the metabolic contributions of astrocytes in the NVU.

Contrast-induced neurotoxicity presented as transient cortical blindness after stent-assisted coiling of a medium-sized unruptured basilar artery aneurysm: A case report and review of the literature

Background: Contrast-induced neurotoxicity is a rare event after endovascular diagnostic procedures or interventions and presents as transient neurological deficit. Herewith, we present a case of reversible complete cortical blindness after uneventful stent-assisted coiling of a medium-sized unruptured basilar artery aneurysm.Case Description: A 70-year-old woman with a medium-sized 10 mm/6 mm wide neck basilar tip aneurysm was planned for endovascular obliteration of the lesion. The procedure was done under general anesthesia. The contrast agent was iso-osmolar, nonionic. The aneurysm was coiled, and a stent was placed in the left posterior cerebral artery achieving sufficient aneurysm packing. No signs of vessel obliteration were observed during the procedure. On awakening of anesthesia, the patient reported complete visual loss. Ophthalmological examination was normal. The patient was brought back to the angio-suite but there were no signs of parent vessel compromise from the endovascular implants or distal vessel occlusion. An MRI of the brain was done showing no signs of brain ischemia, just mild brain edema in both occipital lobes. Given the results of the radiological studies and clinical presentation, the diagnosis of contrast-induced neurotoxicity was accepted. In 72 h, the patient had complete resolution of the visual loss and was discharged home with no additional neurological worsening.Conclusion: Contrast-induced neurotoxicity is a rare event that can occur after uneventful endovascular interventions of the brain vessels. Knowledge of this rare complication, after exclusion of all other possible reversible causes, is important for the treatment and prognosis of the patient.

ANESTHESIA PECULIARITIES IN BEACH CHAIR POSITION (LITERATURE REVIEW)

Beach chair position (BCP) that is applied for shoulder surgery has a number of advantages for surgeons, but it may lead to intraoperative hypotension, bradycardia and postoperative neurologic complications. Objective of the publication is to review up-to-date literature to emphasize complications related to BCP and methods of their monitoring and prophylaxis. Methods. We have analyzed publications from Google Scholar, PubMed, and specialized scientificjournals databases. Results. In orthopedic practice the main types of surgical positions that are used for shoulder surgery are the next: semi-BCP — 30°, BCP — 60°, Semi-upright sitting position — 90°. In spite of its correlations with hemodynamic changes the tilt angle is rarely measured in clinical practice. The etiology of nervous system impairment is thought to be hypotension and subsequent brain hypoperfusion that is induced by BCP under generalanesthesia. Blood pressure at the standard brachial level is significantly higher than at the meatus acoustic level. That is why today the safety level of blood pressure for BCP surgery is not clearly estimated. The majority of clinical investigations have shown that BCP leads to decreasing of regional cerebral blood flow and brain oxygenation. The high incidence of cerebral desaturation events in BCP (more than 50 %) require its accurate monitoring. The most widely used method is NIRS (near-infrared spectroscopy). Other methods including Doppler scanning of brain vessels and jugular saturation has limited clinical using. In majority of trials of cerebral desaturation events has shown to have controversial impact on postoperative cognitive dysfunction. Serum neurospecific proteins examination may be a perspective method of further investigations for neurologic impairment after surgeries in BCP.

Abstract 163: Potential Therapeutic Effects Of Angiopoietin-2 Inhibition On Rescuing Hereditary Hemorrhagic Telangiectasia Associated Cerebrovascular Defects

Introduction: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular disease characterized by arteriovenous malformations (AVMs), which are abnormal, enlarged connections between arteries and veins that are prone to hemorrhage. AVMs often form in the brain and can lead to stroke. Mutations in endoglin (Eng), activin receptor-like kinase 1 (Alk1) or smad-related protein 4 (Smad4) cause HHT. Endothelial cell (EC) specific knock out of Alk1, Eng, or Smad4 in mice mimics HHT vascular defects, including AVM formation. We showed that Smad4 directly repressed transcription of the critical pro-angiogenic factor Angiopoietin-2 (Ang2) in ECs and that in Smad4-HHT mice, Ang2 /ANG2 levels are robustly and ectopically increased in ECs. By inhibiting Ang2, we prevented and rescued AVMs and normalized retinal vasculature. Since Smad4 is a central transcription factor in the TGF-β signaling pathway and a downstream effector of the Eng and Alk1 co-receptors, we hypothesized that Ang2 inhibition may universally normalize HHT vascular phenotypes. Methods: Blue latex dye perfusion methods were used to visualize and characterize cerebrovascular defects in HHT mouse models (n=5~7). RNA-seq was performed on isolated brain ECs (iBECs) to further define molecular phenotypic characteristics (n=5). In situ hybridization on brain slices (n=3) and ELISA on whole brain lysate (n=3~9) were performed to confirm elevated Ang2 RNA and protein levels. Ang2 inhibitor was delivered via intraperitoneal injection, followed by cerebrovascular assessments (n=5~9). Results: We found that brain AVMs are present in Smad4-, Alk1-, and Eng-HHT mutants, with all models displaying elevated Ang2 levels. RNA-seq of iBECs in Smad4-, Alk1-, and Eng-HHT models reveals 5502, 5307, and 1659 differentially expressed genes in respective mutants compared to controls. Data set comparisons revealed common, increased pro-angiogenic genes, which helped to define the HHT-specific angiogenic profile. Moreover, Ang2 inhibition decreased Smad4-HHT’s brain vessel diameter and Alk1-HHT’s brain vessel density, and prevented brain AVM formation in Eng-HHT mice. In conclusion, Ang2 inhibition partially normalized cerebrovascular defects in Smad4- and Alk1-HHT mice, and completely in Eng-HHT mice.

Quantifying cerebral blood flow in the whole brain in a diffusion model with multiple sources from cerebrovascular structures

AbstractVarious imaging techniques have been developed to visualize the three‐dimensional structures of the brain and cerebrovascular vessels. Recently, several imaging techniques have allowed the measurement of cerebral blood flow (CBF) in the whole brain. Despite the rapid development of imaging techniques, numerical methods of predicting CBF are still challenging, due to the complexity of cerebrovascular structure modeling at the clinical level. Additionally, simulation models for oxygen and mass transport from the vasculature to tissues are not available at the clinical level due to the lack of knowledge in the field of microvascular transport. In this study, we propose a computational method to quantify CBF in the whole brain, linking cerebrovascular transport, and brain tissue perfusion. To simplify the linking process, the microvascular transport of blood was treated as a diffusion process. The concentration of CBF was predicted using our novel computational method. Furthermore, we investigated changes in CBF in cases where the blood supply to specific areas of the brain were blocked by disrupted vessels.

Neurocoagulation from a Mechanistic Point of View in the Central Nervous System.

Coagulation mechanisms are critical for maintaining homeostasis in the central nervous system (CNS). Thrombin, an important player of the coagulation cascade, activates protease activator receptors (PARs), members of the G-protein coupled receptor family. PAR1 is located on neurons and glia. Following thrombin activation, PAR1 signals through the extracellular signal-regulated kinase pathway, causing alterations in neuronal glutamate release and astrocytic morphological changes. Similarly, the anticoagulation factor activated protein C (aPC) can cleave PAR1, following interaction with the endothelial protein C receptor. Both thrombin and aPC are expressed on endothelial cells and pericytes in the blood-brain barrier (BBB). Thrombin-induced PAR1 activation increases cytosolic Ca2+ concentration in brain vessels, resulting in nitric oxide release and increasing F-actin stress fibers, damaging BBB integrity. aPC also induces PAR1 activation and preserves BBB vascular integrity via coupling to sphingosine 1 phosphate receptors. Thrombin-induced PAR1 overactivation and BBB disruption are evident in CNS pathologies. During epileptic seizures, BBB disruption promotes thrombin penetration. Thrombin induces PAR1 activation and potentiates N-methyl-D-aspartate receptors, inducing glutamate-mediated hyperexcitability. Specific PAR1 inhibition decreases status epilepticus severity in vivo. In stroke, the elevation of brain thrombin levels further compromises BBB integrity, with direct parenchymal damage, while systemic factor Xa inhibition improves neurological outcomes. In multiple sclerosis (MS), brain thrombin inhibitory capacity correlates with clinical presentation. Both thrombin inhibition by hirudin and the use of recombinant aPC improve disease severity in an MS animal model. This review presents the mechanisms underlying the effects of coagulation on the physiology and pathophysiology of the CNS.

Первая доклиническая ангиоспастическая фаза ретинопатии недоношенных

Purpose. To evaluate the role of the first preclinical phase in the pathogenesis of retinopathy of prematurity (ROP). Material and methods. 642 premature babies were examined. The gestational age at the time of birth was up to 30 weeks and the weight was up to 1500 g. Ophthalmological monitoring was carried out from 28–30 weeks of postconceptional gestational age. Indirect ophthalmoscopy, digital calibration of retinal vessels, and studies on a wide-field retinal pediatric camera were performed. Dopplerography data of the blood flow in the brain vessels and in the ocular artery were analyzed in 28 children (56 eyes). The partial pressure of oxygen (pO2) and carbon dioxide (pCO2) in capillary blood was studied using Radiometer ABL800 FLEX gas analyzer (normal levels of pO2 are 40–60 mmHg, pCO2 is 35–45 mmHg). Results. It was revealed that the lower the degree of maturity of the child’s body was, the more often retinal arteriospasm was detected. In children with a postconceptional age of 25–27 weeks, arteriospasm was detected in 82% of cases, at 28 – 29 weeks – in 67%, 30 – 32 weeks – in 54% of cases. The degree of angiospasm correlates with a high index of blood flow resistance in the brain vessels and the ocular artery. The predominance of a high index of blood flow resistance in more premature infants with low body weight was revealed.The index of resistance of brain vessels 0.8 and higher, according to dopplerography, is a critical indicator of the threat of ROP development in a premature baby. Conclusion. During retinopathy of prematurity, it is important to detect the first preclinical, antispasmodic phase of ROP development, which lasts about one month and until now practically does not attract the attention of ophthalmologists. In this phase, the pathogenesis of pathological angiogenesis is formed. Further study of the preclinical phase will radically revise the strategy and tactics of diagnosis and treatment of RP. Key words: retinopathy of prematurity, first preclinical angiospastic ROP phase, active ROP phase, scarring ROP phase, autoregulation of retinal vessels, hypoxic and hypercapnic drives.

Closed‐Loop Temperature‐Controlled Magnetic Hyperthermia Therapy with Magnetic Guidance of Superparamagnetic Iron‐Oxide Nanoparticles

AbstractHyperthermia therapy eliminates cancer cells by heating them above physiological temperatures. Superparamagnetic iron oxide nanoparticles (SPIONs) are promising for targeted hyperthermia therapy because of their excellent heating efficiency, biocompatibility, and active magnetic navigation. When exposed to a high‐frequency alternating magnetic field (AMF), SPIONs dissipate heat to damage cancer cells. Accurate temperature control is crucial for safe and efficient hyperthermia therapy. A closed‐loop temperature controller to control the temperature and heating rate by adjusting AMF’s strength, thereby enabling controllable hyperthermia therapy. Under a low‐frequency rotating magnetic field (RMF), the SPIONs form chains which can be actively manipulated towards the target by adjusting RMF’s direction, followed by AMF exposure for hyperthermia therapy. The SPIONs are precisely manipulated in a microfluidic chip and rat brain vessels ex vivo, highlighting the potential for targeted position control. Last, in vitro, and in vivo hyperthermia treatments are performed on human prostate cancer cells (PC3) and a PC3 xenograft mouse model using the proposed temperature controller, with tracking errors under 0.5°C and significant reduction in cancer cell viability and tumor volume. The magnetic locomotion with RMF, and the controlled heating using AMF, show the feasibility of using SPIONs for targeted hyperthermia therapy.

Cerebrovascular microRNA Expression Profile During Early Development of Alzheimer's Disease in a Mouse Model.

Emerging evidence demonstrates association of Alzheimer's disease (AD) with impaired delivery of blood oxygen and nutrients to and throughout the brain. The cerebral circulation plays multiple roles underscoring optimal brain perfusion and cognition entailing moment-to-moment blood flow control, vascular permeability, and angiogenesis. With currently no effective treatment to prevent or delay the progression of AD, cerebrovascular microRNA (miRNA) markers corresponding to post-transcriptional regulation may distinguish phases of AD. We tested the hypothesis that cerebrovascular miRNA expression profiles indicate developmental stages of AD pathology. Total RNA was isolated from total brain vessel segments of male and female 3xTg-AD mice [young, 1-2 mo; cognitive impairment (CI), 4-5 mo; extracellular amyloid-β plaques (Aβ), 6-8 mo; plaques+neurofibrillary tangles (AβT), 12-15 mo]. NanoString technology nCounter miRNA Expression panel for mouse was used to screen for 599 miRNAs. Significant (p < 0.05) downregulation of various miRNAs indicated transitions from young to CI (e.g., let-7g & miR-1944, males; miR-133a & miR-2140, females) and CI to Aβ (e.g., miR-99a, males) but not from Aβ to AβT. In addition, altered expression of select miRNAs from overall Pre-AD (young + CI) versus AD (Aβ+ AβT) were detected in both males (let-7d, let-7i, miR-23a, miR-34b-3p, miR-99a, miR-126-3p, miR-132, miR-150, miR-151-5p, miR-181a) and females (miR-150, miR-539). Altogether, at least 20 cerebrovascular miRNAs effectively delineate AD versus Pre-AD pathology. Using the 3xTg-AD mouse model, these data demonstrate that cerebrovascular miRNAs pertaining to endothelial function, vascular permeability, angiogenesis, inflammation, and Aβ/tau metabolism can track early development of AD.

Extracting 3D Angiography Data from Simulated Computed Tomography Angiography Scans Using Low Iodine Contrast Agent

The purpose of this research is to investigate the feasibility of using low contrast agent concentration with X-ray computed tomography in visualizing and diagnosing the human vascular system while minimizing the risk of toxicity to the patient. This research investigated the effect of several iodine contrast agent concentrations on the ability to extract and visualize human vessels using simulated computed tomography scans. Monte Carlo simulation was used to perform these computed tomography acquisitions. The simulated patient was based on actual computed tomography angiography data, where a technique was developed to simulate brain vessels with contrast agents ranging from 0 mg to 20 mg of iodine. The simulation used segmented patient data along with basic image processing techniques to model the various levels of iodine concentrations. Cone beam computed tomography projections of a patient injected with and without iodine were acquired in the simulations. Subtraction of the corresponding projections was performed to generate images caused by the contrast agent. Then, histogram analysis of these differences was used to assess the validity of extracting and visualizing the human vessels. The smallest amount of iodine, 0.5 mg, helped better visualize the brain vessels and 2 mg of iodine was high enough to show almost 90% of the vessels. Additionally, the vessels were clearly visible in all the subtracted images. This research showed very promising outcomes in using low concentrations of iodine. Thus, this study proposes for the pharmaceutical companies and others interested to clinically investigate and evaluate the efficacy of using low concentrations of iodine and the associated side effects.

Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound.

Brain tumors are particularly challenging malignancies, due to their location in a structurally and functionally distinct part of the human body - the central nervous system (CNS). The CNS is separated and protected by a unique system of brain and blood vessel cells which together prevent most bloodborne therapeutics from entering the brain tumor microenvironment (TME). Recently, great strides have been made through microbubble (MB) ultrasound contrast agents in conjunction with ultrasound energy to locally increase the permeability of brain vessels and modulate the brain TME. As we elaborate in this review, this physical method can effectively deliver a wide range of anticancer agents, including chemotherapeutics, antibodies, and nanoparticle drug conjugates across a range of preclinical brain tumors, including high grade glioma (glioblastoma), diffuse intrinsic pontine gliomas, and brain metastasis. Moreover, recent evidence suggests that this technology can promote the effective delivery of novel immunotherapeutic agents, including immune check-point inhibitors and chimeric antigen receptor T cells, among others. With early clinical studies demonstrating safety, and several Phase I/II trials testing the preclinical findings underway, this technology is making firm steps towards shaping the future treatments of primary and metastatic brain cancer. By elaborating on its key components, including ultrasound systems and MB technology, along with methods for closed-loop spatial and temporal control of MB activity, we highlight how this technology can be tuned to enable new, personalized treatment strategies for primary brain malignancies and brain metastases.

Fluorescently-tagged magnetic protein nanoparticles for high-resolution optical and ultra-high field magnetic resonance dual-modal cerebral angiography.

Extremely small paramagnetic iron oxide nanoparticles (FeMNPs) (<5 nm) can enhance positive magnetic resonance imaging (MRI) contrast by shortening the longitudinal relaxation time of water (T1), but these nanoparticles experience rapid renal clearance. Here, magnetic protein nanoparticles (MPNPs) are synthesized from protein-conjugated citric acid coated FeMNPs (c-FeMNPs) without loss of the T1 MRI properties and tagged with fluorescent dye (f-MPNPs) for optical cerebrovascular imaging. The c-FeMNPs shows average size 3.8 ± 0.7 nm with T1 relaxivity (r1) of 1.86 mM-1 s-1 and transverse/longitudinal relaxivity ratio (r2/r1) of 2.53 at 11.7 T. The f-MPNPs show a higher r1 value of 2.18 mM-1 s-1 and r2/r1 ratio of 2.88 at 11.7 T, which generates excellent positive MRI contrast. In vivo cerebral angiography with f-MPNPs enables detailed microvascular contrast enhancement for differentiation of major blood vessels of murine brain, which corresponds well with whole brain three-dimensional time-of-flight MRI angiograms (17 min imaging time with 60 ms repetition time and 40 μm isotropic voxels). The real-time fluorescence angiography enables unambiguous detection of brain capillaries with diameter < 40 μm. Biodistribution examination revealed that f-MPNPs were safely cleared by the organs like the liver, spleen, and kidneys within a day after injection. Blood biochemical assays demonstrated no risk of iron overload in both rats and mice. With hybrid neuroimaging technologies (e.g., MRI-optical) on the rise, f-MPNPs built on this platform can generate exciting neuroscience applications.

Craniotomy for acute monitoring of pial vessels in the rodent brain

A growing awareness for vascular contribution to pathogenesis of brain diseases increases the need for techniques that allow high-resolution imaging and quantification of changes in function and structure of cerebral microvessels. Cerebral vessels are very sensitive structures, making them vulnerable for injury. In addition, they are uniquely characterized with the blood-brain barrier, and an extra caution is required during procedures that involve engagement of cerebral vessels (i.e., craniotomy).Using state of the art facilities, including 3D intravital microscope, we describe here in details:•The steps and equipment required for drilling a craniotomy and removing of the dura, while keeping brain parenchyma and vessels intact. This enables long duration of live and direct monitoring of pial vessels and imaging of BBB permeability.•We present the craniotomy procedure that relevant and compatible with imaging pial vessels and monitoring the blood-brain barrier in small rodents.

Microglial function for synapses and vessels in physiological and pathological brain

Microglial function for synapses and vessels in physiological and pathological brain

Systemic lupus erythematosus: a rare clinical image.

Systemic lupus erythematosus (SLE), is the most common type of lupus. Systemic lupus erythematous is an autoimmune disease in which the immune system attacks its tissues, causing widespread inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. A 12-year-girl visited the outpatient department with the complaint of skin lesions (red color) over sun-exposed areas on the hand, feet, and face. Oral mucosal bleeding, joint pain including knee, shoulder, elbow, and wrist. On physical examination, photosensitive rash and oral bleeding were observed. Laboratories investigation revealed the patient had systemic lupus erythematosus. The patient was referred to the dermatology department for further medical management.