Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of CaV1.2 Channel Function in Cerebral Arteries of Hypertensive Rats.

BACKGROUND: Hypertension is a major, prevalent risk factor for the development and progression of cerebrovascular disease. Regular exercise has been recommended as an excellent choice for the large population of individuals with mild-to-moderate elevations in blood pressure, but the mechanisms that underlie its vascular-protective and antihypertensive effects remain unknown. Here, we describe a mechanism by which myocyte AKAP150 (A-kinase anchoring protein 150) inhibition induced by exercise training alleviates voltage-dependent L-type Ca2+ channel (CaV1.2) activity and restores cerebral arterial function in hypertension. METHODS: Spontaneously hypertensive rats and newly generated smooth muscle-specific AKAP150 knockin mice were used to assess the role of myocyte AKAP150/CaV1.2 channel in regulating cerebral artery function after exercise intervention. RESULTS: Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased CaV1.2 activity and Ca2+ influx of cerebral arterial myocyte, thus enhancing vascular tone in spontaneously hypertensive rats. Smooth muscle-specific AKAP150 knockin mice were hypertensive with higher CaV1.2 channel activity and increased vascular tone. Furthermore, treatment of Ang II (angiotensin II) resulted in a more pronounced increase in blood pressure in smooth muscle-specific AKAP150 knockin mice. Exercise training significantly reduced arterial myocyte AKAP150 expression and alleviated CaV1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle-specific AKAP150 knockin mice. AT1R (AT1 receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II-involved AT1R-AKAP150 association in myocytes of hypertension. CONCLUSIONS: The current study demonstrates that aerobic exercise ameliorates CaV1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension.

Proteomic mapping reveals dysregulated angiogenesis in the cerebral arteries of rats with early-onset hypertension.

Hypertension is associated with the presence of vascular abnormalities, including remodeling and rarefaction. These processes play an important role in cerebrovascular disease development; however, the mechanistic changes leading to these diseases are not well characterized. Using data-independent acquisition-based mass spectrometry analysis, here we determined the protein changes in cerebral arteries in pre- and early-onset hypertension from the spontaneously hypertensive rat (SHR), a model that resembles essential hypertension in humans. Our analysis identified 125 proteins with expression levels that were significantly upregulated or downregulated in 12-week-old spontaneously hypertensive rats compared to normotensive Wistar Kyoto rats. Using an angiogenesis enrichment analysis, we further identified a critical imbalance in angiogenic proteins that promoted an anti-angiogenic profile in cerebral arteries at early onset of hypertension. In a comparison to previously published data, we demonstrate that this angiogenic imbalance is not present in mesenteric and renal arteries from age-matched SHRs. Finally, we identified two proteins (Fbln5 and Cdh13), whose expression levels were critically altered in cerebral arteries compared to the other arterial beds. The observation of an angiogenic imbalance in cerebral arteries from the SHR reveals critical protein changes in the cerebrovasculature at the early onset of hypertension and provides novel insights into the early pathology of cerebrovascular disease.

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. METHODS: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 (microRNA-5112) in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. Adenovirus-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. RESULTS: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that CircOGDH expression was positively correlated with the size of penumbra in patients with AIS. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, the expression of CircOGDH in brain tissue was closely related to that in the serum of middle cerebral artery occlusion mice. Finally, we found that CircOGDH was highly expressed in plasma exosomes of patients with AIS compared with those in noncerebrovascular disease individuals. CONCLUSIONS: These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemia neuronal viability, and is enriched in neuron-derived exosomes in the peripheral blood, exhibiting a predictive biomarker of penumbra in patients with AIS.

Paternal preconception alcohol consumption increased Angiotensin II-mediated vasoconstriction in male offspring cerebral arteries via oxidative stress-AT1R pathway.

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca2+ ) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BKC a ) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.

[Reversible cerebral vasoconstriction syndrome : A rare cause of stroke]. / Reversibles zerebrales Vasokonstriktionssyndrom : Eine seltene Schlaganfallursache.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex and etiologically diverse neurovascular disorder that typically presents with severe thunderclap headaches (TCH) as the primary symptom, accompanied by reversible vasoconstriction of the cerebral arteries. The clinical course may include focal neurological deficits or epileptic seizures. There are two types: idiopathic RCVS and secondary RCVS, the latter triggered by various substances, medical interventions, or diseases. In clinical practice, various medical specialists may initially encounter this condition, underscoring the importance of accurate recognition and diagnosis of RCVS. The clinical course often appears monophasic and self-limiting, with recurrences reported in only 1.7% of cases annually. Complications such as cerebral hemorrhages and cerebral ischemia can lead to death in 5-10% of cases. This article utilizes a case study to explore RCVS, its complications, and the diagnostic procedures involved.

Endovascular Therapy or Medical Management Alone for Isolated Posterior Cerebral Artery Occlusion: A Multicenter Study.

BACKGROUND: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown. METHODS: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration. RESULTS: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P=0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P=0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P=0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P<0.0001). CONCLUSIONS: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Editorial comment: Changes in high-resolution vessel wall imaging features before and after PTAS for severe intracranial artery stenosis: predicting clinical outcomes within one year.

KEY POINTS: • Periprocedural HR-VWI plays an important role in the prediction of one-year outcomes of SICAS patients who underwent PTAS.• The study further expands the application of lesion wall enhancement on HR-VWI as a predictor of RCIS after PTAS.

Structural and Functional Characteristics of Cerebral Arteries as an Explanation for Clinical Syndromes Limited to the Brain.

Vascular disease affects many different arterial beds throughout the body. Yet the brain is susceptible to several vascular disorders that either are not found in other parts of the body or when found are much less likely to cause clinical syndromes in other organs. This specific vulnerability of the brain may be explained by structural and functional differences between the vessels of the brain and those of vessels in other parts of the body. In this review, we focus on how cerebrovascular anatomy and physiology may make the brain and its vessels more susceptible to unique vascular pathologies. To highlight these differences, we use our knowledge of five diseases and syndromes that most commonly manifest in the intracranial vasculature. For each, we identify characteristics of the intracranial arteries that make them susceptible to these diseases, while noting areas of uncertainty requiring further research.

Multiple dissecting intracranial and extracranial aneurysms in rheumatoid arthritis: a rare case.

A 52 year old female with a history of rheumatoid arthritis (RA) and persistently raised levels of serum rheumatoid factor and cyclic citrunillated peptide, presented with dissecting aneurysms at the right internal carotid artery, and intact aneurysms at the supraclinoid segment and opening of the right opthalmic artery. Coil embolization was performed. The patient developed an ischaemic stroke two days later.Intra and extra-cranial large vessel aneurysms in RA have rarely been reported in the literature. RA patients with persistent systemic inflammation are at increased risk of developing vascular complications and ischaemic stroke. Here, high levels of tissue-deposited immune complexes may have resulted in cerebral artery vasculopathy. Risk stratification for the development of vascular complications, including cranial aneurysms and ischaemic stroke, in RA patients with poorly controlled systemic inflammation, is important; especially when we consider the neurological sequelae associated with dissecting cerebral aneurysms, cerebral infarction and surgical intervention.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

High-Resolution Vessel Wall MR Imaging in Diagnosis and Length Measurement of Cerebral Arterial Thrombosis: A Feasibility Study.

BACKGROUND: Detecting and measuring intraluminal thrombus has prognostic and therapeutic implications for stroke patients. PURPOSE: To investigate the feasibility of 3D isotropic high-resolution T1w-CUBE imaging to detect and measure intraluminal thrombus in stroke patients. STUDY TYPE: Retrospective. SUBJECTS: A total of 93 patients with acute (N = 39) and subacute (N = 54) stroke. FIELD STRENGTH/SEQUENCE: A 3.0 T/spin-echo echo-planar diffusion-weighted imaging (DWI), high-resolution T1w-CUBE imaging and 3D flow compensated gradient-echo susceptibility-weighted imaging (SWI). ASSESSMENT: Data assessment was performed by three neuroradiologists with 11, 13, and 20 years of clinical experience. The accuracy of T1W-CUBE and SWI in diagnosing thrombosis was compared by using digital subtraction angiography (DSA) as the reference. For thrombus length measurement, the image quality of proximal and distal thrombus of T1w-CUBE images was first evaluated with a 4-point rating system. Then, the proximal and distal positions to lesions were determined on T1w-CUBE images and compared with those from DSA acquired during endovascular reperfusion therapy. If comparable both locations were found between CUBE and DSA, CUBE imaging can thus be considered for accurate measurement of thrombus length. STATISTICAL TESTS: Fleiss' Kappa; the area under the receiver operating characteristic (ROC) curve (AUC); Pearson's chi-squared test with Yates' continuity correction. RESULTS: Moderate-to-good interobserver agreements were validated with all Kappa coefficients higher than 0.40 in thrombus diagnosis and measurement. CUBE imaging showed higher clinical efficacy than SWI (AUC: 0.966 vs. 0.850) in thrombus diagnosis. Additionally, high quality of CUBE imaging was confirmed with 3 or 4 points rated by all three observers. Compared to intraoperative DSA, T1w CUBE showed consistent proximal and distal positions of thrombi in 16 of the 18 patients, validating the accuracy of T1w-CUBE in measuring thrombus length. DATA CONCLUSION: T1w-CUBE imaging has potential to facilitate diagnosis and measurement of intraluminal thrombus. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Effects of Levodopa Therapy on Cerebral Arteries and Perfusion in Parkinson's Disease Patients.

BACKGROUND: Levodopa is the most-commonly used therapy for Parkinson's Disease (PD). Imaging findings show increased cerebral blood flow (CBF) response to levodopa, but the artery morphological change is less studied. PURPOSE: To investigate the effect of levodopa on cerebral arteries and CBF. STUDY TYPE: Prospective. POPULATION: 57 PD patients (56 ± 10 years, 26 males) and 17 age-matched healthy controls (AMC, 57 ± 9 years, 9 males) were scanned at baseline (OFF). Patients were rescanned 50 minutes after taking levodopa (ON). FIELD STRENGTH AND SEQUENCE: 3 T; Simultaneous noncontrast angiography intraplaque imaging (SNAP) based on turbo field echo; Pseudo-continuous arterial spin labeling (PCASL) based on echo-planner imaging. ASSESSMENT: The Unified Parkinson's Disease Rating Scale (UPDRS-III) was used to assess the disease severity. Length and radius of arteries were measured from SNAP images. CBF was calculated from PCASL images globally and regionally. STATISTICAL TESTS: Mann Whitney U tests were conducted in comparing PD vs. AMC. Wilcoxon matched-pairs signed rank tests were used in comparing OFF vs. ON, and the more-affected vs. the less-affected hemisphere in PD. Linear regressions were performed to test the correlations of neuroimaging findings with behavioral changes. Significance threshold was P < 0.05 with Bonferroni correction. RESULTS: PD patients were identified with significantly lower CBF (PD OFF Mean = 40.15 ± 5.99, AMC Mean = 43.48 ± 6.21 mL/100 g/min) and shortened total artery length (PD OFF Mean = 5851.07 ± 1393.45, AMC Mean = 7479.16 ± 1335.93 mm). Levodopa elevated CBF of PD brains (PD ON Mean = 41.48 ± 6.32 mL/100 g/min) and expanded radius of proximal arteries. Artery radius change significantly correlated with CBF change in corresponding territories (r = 0.559 for Internal Carotid Arteries, r = 0.448 for Basilar Artery, and r = 0.464 for Middle Cerebral Artery M1). Global CBF significantly related to UPDRS-III (r = -0.391) post-levodopa. DATA CONCLUSION: Levodopa can increase CBF by dilating proximal arteries. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.

Cerebral white matter vasculature: still uncharted?

White matter vasculature plays a major role in the pathophysiology of permanent neurological deficits following a stroke or progressive cognitive alteration related to small vessel disease. Thus, knowledge of the complex vascularization and functional aspects of the deep white matter territories is paramount to comprehend clinical manifestations of brain ischaemia. This review provides a structured presentation of the existing knowledge of the vascularization of the human cerebral white matter from seminal historical studies to the current literature. First, we revisit the highlights of prenatal development of the endoparenchymal telencephalic vascular system that are crucial for the understanding of vessel organization in the adult. Second, we reveal the tangled history of debates on the existence, clinical significance and physiological role of leptomeningeal anastomoses. Then, we present how conceptions on white matter vascularization transitioned from the mixed ventriculopetal/ventriculofugal theory, in which a low-flow area was interposed in between concurrent arterial flows, to the purely ventriculopetal theory. The latter model explains variable white matter sensitivity to ischaemia by various organizations of ventriculopetal vessel terminals having different origin/length properties and interconnection patterns. Next, arteries supplying primarily the white matter are described according to their length and overall structure. Furthermore, the known distribution territories, to date, are studied in relation to primary anatomical structures of the human cerebral white matter, emphasizing the sparsity of the 'ground truth' data available in the literature. Finally, the implications for both large vessel occlusion and chronic small vessel disease are discussed, as well as the insights from neuroimaging. All things considered, we identify the need for further research on deep white matter vascularization, especially regarding the arterial supply of white matter fibre tracts.

Thrombectomy of symptomatic isolated occlusions of posterior cerebral arteries in segment P1 and P2 in acute stroke treatment.

BACKGROUND: Interventional stroke treatments for occlusions of the posterior circulation are established procedures. However, there are limited data on the treatment of isolated symptomatic P1 and P2 occlusions, which we have examined in this study. PURPOSE: To investigate the mechanical thrombectomy of distal posterior occlusions. MATERIAL AND METHODS: Retrospectively, data from patients with isolated P1 and P2 occlusions treated with MT were evaluated. Successful reperfusions have been defined as modified thrombolysis in cerebral infarct (mTICI) Grade 2b-3. A good clinical outcome was defined as a 90-day modified Rankin score 0-2. RESULTS: All 79 treated patients were primarily aspirated. Stent retrievers were used secondarily in nine patients. Successful reperfusion was achieved in 95% of patients. Of the patients, 57% had a favorable clinical outcome after 90 days. CONCLUSION: Mechanical thrombectomy with first line aspiration of symptomatic P1 and P2 occlusions is a safe and effective procedure.

Nanoscale coupling of junctophilin-2 and ryanodine receptors regulates vascular smooth muscle cell contractility.

Junctophilin proteins maintain close contacts between the endoplasmic/sarcoplasmic reticulum (ER/SR) and the plasma membrane in many types of cells, as typified by junctophilin-2 (JPH2), which is necessary for the formation of the cardiac dyad. Here, we report that JPH2 is the most abundant junctophilin isotype in native smooth muscle cells (SMCs) isolated from cerebral arteries and that acute knockdown diminishes the area of sites of interaction between the SR and plasma membrane. Superresolution microscopy revealed nanometer-scale colocalization of JPH2 clusters with type 2 ryanodine receptor (RyR2) clusters near the cell surface. Knockdown of JPH2 had no effect on the frequency, amplitude, or kinetics of spontaneous Ca2+ sparks generated by transient release of Ca2+ from the SR through RyR2s, but it did nearly abolish Ca2+ spark-activated, large-conductance, Ca2+-activated K+ (BK) channel currents. We also found that JPH2 knockdown was associated with hypercontractility of intact cerebral arteries. We conclude that JPH2 maintains functional coupling between RyR2s and BK channels and is critically important for cerebral arterial function.

Aberrant course of the petrous internal carotid artery associated with ipsilateral type 1 proatlantal artery.

PURPOSE: To describe an extremely rare case of an aberrant course of the petrous internal carotid artery (ICA) associated with an ipsilateral type 1 proatlantal artery (PA) that was diagnosed by cerebral magnetic resonance (MR) angiography. CASE REPORT: The patient was a 64-year-old man with double vision. Cerebral MR imaging and MR angiography were subsequently performed using a 1.5-T scanner. MR angiography showed an aberrant course of the petrous right ICA that was associated with right type 1 PA. The left vertebral artery (VA) and proximal right VA were absent. DISCUSSION: An aberrant course of the petrous ICA is rare but clinically significant, because it is dangerous during middle ear surgery. Type 1 PA is an extremely rare type of persistent fetal anastomosis between the carotid and vertebrobasilar systems. Type 1 PA is also clinically significant, because it is dangerous during craniovertebral junction surgery. We found no similar cases in the relevant English-language literature. CONCLUSION: Although both variations were seen ipsilaterally and were located relatively close to each other, the embryological development of these variations is quite different. In addition, no similar case has been reported previously. Thus, these may have formed incidentally.

[Small focal cerebral ischemic changes caused by hypertension and tandem atherostenosis of the cerebral arteries]. / Melkoochagovye ishemicheskie izmeneniya golovnogo mozga, obuslovlennye arterial'noi gipertoniei i tandemnym aterostenozom tserebral'nykh arterii.

Postmortem studies are of great importance in evaluating the effectiveness of clinical, diagnostic, therapeutic, and preventive measures aimed at combating a social disease, such as dyscirculatory encephalopathy, the leading causes of which are hypertension and atherosclerosis. The complexity of these studies is largely determined by a variety of brain changes with the frequent concurrence of hypertension and severe cerebral atherosclerosis and, at the same time, the similarity of some changes, for example, the localization and size of hypertensive and atherosclerotic lacunar infarcts. The paper describes a case of dyscirculatory encephalopathy with multiple small focal cerebral ischemic changes caused by both hypertension and athero-stenosis of several arteries in both the brain carotid systems and the vertebrobasilar system, namely tandem stenoses. It has been established that small infarcts in tandem stenosis can result from adaptive processes in the intracranial arteries. These infarcts have some features of localization, such as the areas of adjacent blood supply to the cerebral hemispheres and cerebellum, as well as the deep regions of the brainstem. It is shown that arterial pathological changes in the ischemic zones permit one to make a differential diagnosis of hypertensive lacunar infarcts and the same infarcts arising in tandem stenoses. In addition, among the typological signs of hypertensive lacunar infarcts, there are enlarged perivascular spaces in the peri-infarct region and ischemic destruction of myelin in the periventricular regions of the brain.

Activation of the Central Renin-Angiotensin System Causes Local Cerebrovascular Dysfunction.

Background and Purpose: Hypertension is a leading risk factor for cerebrovascular disease and loss of brain health. While the brain renin-angiotensin system (RAS) contributes to hypertension, its potential impact on the local vasculature is unclear. We tested the hypothesis that activation of the brain RAS would alter the local vasculature using a modified deoxycorticosterone acetate (DOCA) model. Methods: C57BL/6 mice treated with DOCA (50 mg SQ; or shams) were given tap H2O and H2O with 0.9% NaCl for 1 to 3 weeks. Results: In isolated cerebral arteries and parenchymal arterioles from DOCA-treated male mice, endothelium- and nitric oxide-dependent dilation was progressively impaired, while mesenteric arteries were unaffected. In contrast, cerebral endothelial function was not significantly affected in female mice treated with DOCA. In males, mRNA expression of renal Ren1 was markedly reduced while RAS components (eg, Agt and Ace) were increased in both brain and cerebral arteries with central RAS activation. In NZ44 reporter mice expressing GFP (green fluorescent protein) driven by the angiotensin II type 1A receptor (Agtr1a) promoter, DOCA increased GFP expression ≈3-fold in cerebral arteries. Impaired endothelial responses were restored to normal by losartan, an AT1R (angiotensin II type 1 receptor) antagonist. Last, DOCA treatment produced inward remodeling of parenchymal arterioles. Conclusions: These findings suggest activation of the central and cerebrovascular RAS impairs endothelial (nitric oxide dependent) signaling in brain through expression and activation of AT1R and sex-dependent effects. The central RAS may be a key contributor to vascular dysfunction in brain in a preclinical (low renin) model of hypertension. Because the brain RAS is also activated during aging and other diseases, a common mechanism may promote loss of endothelial and brain health despite diverse cause.

Deep Cerebral Perforators: Anatomical Distribution and Clinical Symptoms: An Overview.

The anatomic distribution of the deep cerebral perforators is considered either a given or subject to enormous variability. Most published overviews on this topic only report findings from a limited number of anatomic dissections, and no attempt has been made to date to provide a comprehensive overview of all published data. A comprehensive literature search was performed on MEDLINE, Embase, and Google Scholar with the help of an information specialist. Three types of studies were included: (1) articles that described the anatomy and distribution territories of perforator groups arising from the arteries of the circle of Willis; (2) studies that evaluated the anatomy of the deep cerebral perforators using imaging techniques; and (3) studies that evaluated either microsurgically or radiologically confirmed perforator occlusion and reported the (magnetic resonance imaging-confirmed) distribution territory of the infarction together with a description of the clinical symptoms associated as a result of the infarction. A total of 2715 articles were screened and 53 were included. Of these, 40 dealt with the anatomic and imaging anatomy of perforator groups (37 reported results of dissections and 3 results of imaging studies), with a total of 2421 hemispheres investigated. Another 13 articles with 680 patients were included that evaluated perforator infarction territories. The deep cerebral perforator distribution shows large variability with poor concordance rates among reported studies, with the exception of the posterior communicating and anterior choroidal artery perforators. Despite the assumption that cerebral perforator anatomy is a given, studies show large variability in the anatomic distribution of various perforator groups. Perforator anatomy and relationships between perforator groups, as well as potential collateral circulation in these territories should be prioritized as a research topic in cerebrovascular disease in the near future.

An evaluation of performance measures for arterial brain vessel segmentation.

BACKGROUND: Arterial brain vessel segmentation allows utilising clinically relevant information contained within the cerebral vascular tree. Currently, however, no standardised performance measure is available to evaluate the quality of cerebral vessel segmentations. Thus, we developed a performance measure selection framework based on manual visual scoring of simulated segmentation variations to find the most suitable measure for cerebral vessel segmentation. METHODS: To simulate segmentation variations, we manually created non-overlapping segmentation errors common in magnetic resonance angiography cerebral vessel segmentation. In 10 patients, we generated a set of approximately 300 simulated segmentation variations for each ground truth image. Each segmentation was visually scored based on a predefined scoring system and segmentations were ranked based on 22 performance measures common in the literature. The correlation of visual scores with performance measure rankings was calculated using the Spearman correlation coefficient. RESULTS: The distance-based performance measures balanced average Hausdorff distance (rank = 1) and average Hausdorff distance (rank = 2) provided the segmentation rankings with the highest average correlation with manual rankings. They were followed by overlap-based measures such as Dice coefficient (rank = 7), a standard performance measure in medical image segmentation. CONCLUSIONS: Average Hausdorff distance-based measures should be used as a standard performance measure in evaluating cerebral vessel segmentation quality. They can identify more relevant segmentation errors, especially in high-quality segmentations. Our findings have the potential to accelerate the validation and development of novel vessel segmentation approaches.