Vascular Brain Damage Research Articles

Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction/Disruption with Increased Risk of Hemorrhagic and Ischemic Stroke.

Globally, cerebral microbleeds (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5 mm, smooth, round, or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences MRI images. CMBs are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and is only expected to continue to grow, we can expect the healthcare burdens associated with CMBs to also grow. Increased numbers (≥10) of CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Herein author highlights that it is essential to learn as much as we can about CMB development, evolution, and their relation to impaired cognition, dementia, and the exacerbation of neurodegeneration.

Clusters of resilience and vulnerability: executive functioning, coping and mental distress in patients with diffuse low-grade glioma

PurposeDiffuse low-grade gliomas (dLGG) often have a frontal location, which may negatively affect patients’ executive functions (EF). Being diagnosed with dLGG and having to undergo intensive treatment can be emotionally stressful. The ability to cope with this stress in an adaptive, active and flexible way may be hampered by impaired EF. Consequently, patients may suffer from increased mental distress. The aim of the present study was to explore profiles of EF, coping and mental distress and identify characteristics of each profile.Methods151 patients with dLGG were included. Latent profile analysis (LPA) was used to explore profiles. Additional demographical, tumor and radiological characteristics were included.ResultsFour clusters were found: 1) overall good functioning (25% of patients); 2) poor executive functioning, good psychosocial functioning (32%); 3) good executive functioning, poor psychosocial functioning (18%) and; 4) overall poor functioning (25%). Characteristics of the different clusters were lower educational level and more (micro)vascular brain damage (cluster 2), a younger age (cluster 3), and a larger tumor volume (cluster 4). EF was not a distinctive factor for coping, nor was it for mental distress. Maladaptive coping, however, did distinguish clusters with higher mental distress (cluster 3 and 4) from clusters with lower levels of mental distress (cluster 1 and 2).ConclusionFour distinctive clusters with different levels of functioning and characteristics were identified. EF impairments did not hinder the use of active coping strategies. Moreover, maladaptive coping, but not EF impairment, was related to increased mental distress in patients with dLGG.

Features of the Background EEG of Alcohol Dependent Patients with Comorbid Exogenous Organic Brain Damage

Background: the range and prevalence of complicating pathologies in alcoholism indicate the need for a thorough examination of patients using modern diagnostic approaches. The aim was to study the indicators of spontaneous electrical activity of the brain in patients with alcohol dependence with comorbid exogenous organic brain damage non-alcoholic nature. Patients and methods: a study of electroencephalograms of 148 men with alcohol dependence using the classification of E.A. Zhirmunskaya (1984) was conducted. Results: based on the hystory data, 85 (57.4%) patients were found to have exogenous organic vascular brain damage (including hypertension in 57 (38.5%) cases, chronic cerebral circulation disorder — in 8 (5.4%), somatoform autonomic dysfunction — in 7 (4.7%)) and traumatic character (mild traumatic brain injury) in 13 (8.8%)) patients. The analysis using Fisher’s exact criterion revealed statistically significant differences between patients with alcohol dependence and alcoholism patients with comorbid exogenous organic brain damage in the frequency of occurrence of various types of electroencephalograms (p < 0.001). The study clearly showed that the presence of exogenous organic brain damage in patients with alcoholism leads to more pronounced functional changes in the brain. Conclusion: early detection of pathological activity on the EEG in patients with alcohol dependence will allow clinicians to carry out appropriate therapeutic and diagnostic measures in a timely manner and will provide additional information necessary for the development of personalized medical rehabilitation programs for patients taking into account their neurophysiological profile.

Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury.

Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.

H-FABP as a Biomarker of Vascular Brain Damage in Transient Ischemic Attack (P3-5.009)

H-FABP as a Biomarker of Vascular Brain Damage in Transient Ischemic Attack (P3-5.009)

Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System <i>in vivo</i>

Introduction. A characteristic manifestation of vascular brain damage is depressive disorders that accompany both acute and chronic disorders of cerebral circulation. Depression not only reduces the patient's quality of life, but also complicates the treatment of basic vascular disease, increases the risk of stroke and death. Therefore, complex therapy of vascular depression includes not only antidepressants, but also basic means to correct the consequences of disorders of cerebral blood flow, including with antiplatelet activity. In this regard, the development of a new molecule based on thietane-containing heterocycles, combining the properties of an antidepressant and an antiplatelet agent.Aim. To conduct a preclinical evaluation of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazol-4 bromide when administered to rats.Materials and methods. A study was conducted of the effect of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietan-3-yl)-1H-1,2,4-triazol-4-bromide on the hemostasis system during intravenous and intragastric administration to healthy white non-linear sexually mature male rats (n = 160). Thromboelastography was performed on a TEG 5000 device, activated with a 0.2 M solution of calcium chloride, Born aggregometry and standard clotting tests to assess the coagulation component of hemostasis.Result and discussion. The findings show that 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide with peroral administration exceeded acetylsalicylic acid by 2.8 times in terms of ED50, and by 1.8 times with intravenous way of administration accordingly. A similar effect of pentoxifylline in the intravenous route of administration was recorded at a concentration of 27.8 mg/kg versus 12.4 mg/kg of compound I. The results of a complex method to assess the state of the hemostasis system indicate a more pronounced antiaggregational effect of compound I compared with pentoxifylline and acetylsalicylic acid.Conclusion. Preclinical studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4 bromide, was demonstrated that a combination of antidepressant and antiplatelet activity, which can serve as a basis for further drug development.

Glycogen Synthase Kinase-3β Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix-intraventricular Hemorrhage of the Preterm Newborn.

Advances in neonatology have significantly reduced mortality rates due to prematurity. However, complications of prematurity have barely changed in recent decades. Germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most severe complications of prematurity, and these children are prone to suffer short- and long-term sequelae, including cerebral palsy, cognitive and motor impairments, or neuropsychiatric disorders. Nevertheless, GM-IVH has no successful treatment. VP3.15 is a small, heterocyclic molecule of the 5-imino-1,2,4-thiadiazole family with a dual action as a phosphodiesterase 7 and glycogen synthase kinase-3β (GSK-3β) inhibitor. VP3.15 reduces neuroinflammation and neuronal loss in other neurodegenerative disorders and might ameliorate complications associated with GM-IVH. We administered VP3.15 to a mouse model of GM-IVH. VP3.15 reduces the presence of hemorrhages and microglia in the short (P14) and long (P110) term. It ameliorates brain atrophy and ventricle enlargement while limiting tau hyperphosphorylation and neuronal and myelin basic protein loss. VP3.15 also improves proliferation and neurogenesis as well as cognition after the insult. Interestingly, plasma gelsolin levels, a feasible biomarker of brain damage, improved after VP3.15 treatment. Altogether, our data support the beneficial effects of VP3.15 in GM-IVH by ameliorating brain neuroinflammatory, vascular and white matter damage, ultimately improving cognitive impairment associated with GM-IVH.

Arterial Hypertension, Structural Damage of the Brain and Cognitive Test

The arterial hypertension cause brain vascular damage (white matter lesion) and the burden and progression determine their cognitive consequences. Therefore, arterial hypertension is considered the main modifiable vascular risk factor for cognitive impairment and dementia. Therefore, the aim of the current study was to evaluate the results of cognitive tests in a sample of hypertensive patients and to establish possible associations with structural brain lesions (atrophy, white matter lesions) identified by magnetic resonance imaging Were included 70 hypertensive patients from Heart-Brain study in Argentina with magnetic resonance imaging and cognitive test. Fazekas scale and the Global Cortical Atrophy were used to quantify the white matter lesions and the brain atrophy, respectively. The Mini-Mental Status Examination, Clock Drawing test and Mini-Boston Naming test were used to evaluate the cognitive status. average age 69.7 ± 10.6 years, 55.7% female). Based on the linear regression analysis, Fazekas scale and cognitive tests were inversely associated. For each grade of increase in Fazekas scale, the clock drawing test (Coef -0.56, CI 95% -1.01 -0.10, p=0.01) and the Mini-mental Status Examination (Coef -0.7, CI 95% -1.27 -0.13, p=0.01) scores decreased. The subcortical atrophy was significantly associated with the clock drawing test (OR 3.29, CI 95% 1.25-8.63; p=0.016). Conclusion: The cognitive tests, particularly the clock drawing test could be used (in the clinical routine practice) as “subrrogate” of the brain structural hypertension-mediated damage.

Sleep disturbances, cortisol, and neuroimaging correlates among memory clinic patients

AbstractBackgroundSleep disturbances are increasingly acknowledged as a preclinical marker for Alzheimer’s disease (AD), however, the mechanisms underlying the association between sleep disturbances and dementia remain unclear. Sleep disturbances may affect AD through brain morphology changes and vascular damage, as sleep disturbances are known to be linked with altered grey‐ and white‐matter integrity. Moreover, sleep and brain changes may be linked with cortisol levels. Sleep disturbances have been proposed to parallel cortisol dysregulation, and older individuals with preclinical AD have altered awakening cortisol, a feature that is intensified among people also suffering from sleep disturbances.MethodThe study is based on 146 memory clinic patients from the Karolinska University Hospital memory clinic (Sweden). Participants are in the age range 47‐86 years and diagnosed with either subjective cognitive impairment or mild cognitive impairment. Self‐reported sleep disturbances are measured by the Karolinska Sleep Questionnaire. Brain imaging (MRI or CT) was used to semi‐quantify brain atrophy using four visual rating scales: Medial Temporal Atrophy, Global Cortical Atrophy, Koedam (posterior brain atrophy) and Fazekas (white‐matter lesions) scales. Lastly, saliva cortisol has been sampled 6 times daily to measure diurnal cortisol patterns.ResultOrdinal logistic regressions show significant associations between sleep disturbances and brain parameters. Insufficient sleep (OR = 1.30, p = 0.048) is associated with greater odds of white‐matter lesions, and apnea (OR = 1.26, p = 0.036) and snoring (OR = 1.38, p = 0.045) are associated with greater odds of posterior brain atrophy. Increased daytime sleepiness is associated with both reduced awakening cortisol (β = ‐0.03, p = 0.025) and a flattened cortisol curve (β = ‐0.04, p = 0.019). Apnea is associated with reduced awakening cortisol (β = ‐0.06, p = 0.013). However, cortisol was not found to significantly interact with sleep in predicting brain outcomes.ConclusionThese results show that various sleep disturbance parameters (short sleep duration, apnea, and snoring) are associated with neuroimaging correlates, while daytime sleepiness and apnea are associated with markers of dysregulated cortisol patterns. The results suggest that neuroimaging correlates and cortisol measures may clarify the mechanisms underlying the associations between sleep disturbance and cognitive impairment, and the combination of objective sleep measures and neuroimaging markers in future studies may further reveal the mechanisms.

Enlarged Perivascular Spaces in a Diverse Community‐based Sample. The Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundEnlarged perivascular spaces (ePVS) have been associated with small vessel disease of the brain (SVD). Nevertheless, the burden, correlates and significance of ePVS have been studied predominantly in White individuals, so the generalizability of these findings to other racial/ethnic groups remains uncertain. Herein, we present an investigation of ePVS in a large, multi‐ethnic, community‐based cohort.MethodePVS volumes were quantified in 1,026 participants (median age 71 years; 47% men) from the Multi‐Ethnic Study of Atherosclerosis, using a fully‐automated deep learning model with 82% lesion‐wise sensitivity. Based on previously‐described clinical rating systems, ePVS were grouped in four brain regions: basal ganglia, thalamus, frontoparietal region, and temporal region, and were normalized to the respective regional volumes. Cognition was assessed with the Cognitive Abilities Screening Instrument, the Digit Symbol Coding, and the Digit Span test. APOE‐ε4 isoforms were estimated from single nucleotide polymorphisms (rs429358,rs7412). The relationships of normalized regional ePVS volumes with demographic and vascular risk factors, neuroimaging indices, cognition, and APOE genotype were explored using generalized linear models.ResultBasal ganglia was the anatomic region with the largest ePVS burden (median[IQR] = 1.9[1.4] % of total regional volume), followed by the frontoparietal region (0.6[0.5]), temporal region (0.4[0.4]), and thalamus (0.3[0.3]) – Figure 1,Table 1. Basal ganglia ePVS volume was positively associated with age, systolic blood pressure (SBP), use of antihypertensives, white matter hyperintensity volume (WMHV), and microbleeds (MBs), and negatively associated with white matter fractional anisotropy (FA) and Black race (Tables 1,2). Thalamic ePVS volume was positively associated with age, use of antihypertensives, WMHV, and MBs, and negatively associated with FA. Frontoparietal ePVS volume was positively associated with SBP, and negatively associated with age. Temporal region ePVS volume was negatively associated with age, Chinese and Hispanic ethnicity. No significant associations were observed between regional ePVS volumes and cognition or APOE genotype.ConclusionIncreased ePVS burden in the basal ganglia and thalamus was associated with hypertension and imaging biomarkers of vascular brain damage in a multi‐ethnic population of older adults, likely reflecting underlying SVD. Compared to other racial/ethnic groups, White race was associated with higher ePVS burden in the basal ganglia and temporal regions.

Macular vessel density in the superficial plexus is not associated to cerebrovascular damage in non‐demented individuals: data from the NORFACE cohort

AbstractBackgroundOptical Coherence Tomography angiography (OCT‐A) is a novel tool that allows the detection of retinal vascular changes. The comparison of OCT‐A measures with brain vascular burden is essential to validate the former as a surrogate of cerebrovascular damage and biomarker of cognitive decline. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus assessed by OCT‐A with measures of cerebrovascular pathology quantified by brain magnetic resonance imaging (MRI) in a cohort of non‐demented individuals.MethodClinical, demographical, APOE ε4 status, amyloid status, OCT‐A and brain MRI data from non‐demented participants of the FACEHBI and BIOFACE studies were included. We analyzed the association of macular VD in four quadrants (superior, nasal, inferior and temporal) with brain vascular burden using the Fazekas scale scores (dichotomized in two categories, 0‐1 vs 2‐3), assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) quantified by Freesurfer assessed in a multiple regression analysis. We additionally explored the associations of macular VD with hippocampal volume, ventricles volume and Alzheimer Disease cortical signature (ADCS) thickness assessed in a multiple regression analysis. All analyses were adjusted for age and dyslipidemia.ResultThe study cohort comprised 188 participants: 89 with subjective cognitive decline (SCD) and 99 with mild cognitive impairment (MCI). Logistic regression analysis showed no significant differences of regional macular VD between the two Fazekas groups (all, p>0.05). Multiple regression analysis showed no significant association of regional macular VD with the volume of WMH (all, p>0.05). Macular VD in the nasal and inferior quadrants were positively associated with hippocampal volume (p = 0.009 and p = 0.021, respectively), but no association was detected with ventricles volume or ADCS thickness (both p>0.05).ConclusionOur study showed that retinal vascular measures (regional macular VD in the superficial vascular plexus) assessed by OCT‐A were not associated with brain vascular damage quantified by the Fazekas scale and the WMH burden n in a cohort of non‐demented research participants with SCD and MCI.

Abstract 18846: A Noninvasive Smartphone Assessment of Aortic Arch Pulse Wave Velocity and Total Arterial Compliance

Introduction: Several clinical studies including a large multiethnic population (Dallas Heart Study) have shown that total arterial compliance (TAC) and aortic arch pulse wave velocity (PWV aa ) are predictors of cardiovascular disease (CVD) events. Dallas Heart Study also showed that PWV aa predicts brain white matter hyperintensity volume independent of cardiovascular risk factors. Recently, Intrinsic Frequency (IF) analysis of carotid pressure waveform from the Framingham Heart Study was used to predict heart failure (HF) events and CVD (Hypertension, 2021 PMID: 33390053). Aim: Our goal was to show the IF method can determine PWV aa and TAC when applied on carotid pulse waveforms obtained from a standard iPhone camera. Methods: The clinical cohort consisted of 120 individuals (40% women) with ages from 20-92 yrs (mean 53 ± 18), including 54 healthy and 66 patients with CVD (22 HF). Phase-contrast magnetic resonance imaging (PC-MRI) and carotid pressure tonometry data were used to compute TAC. PWV aa values were obtained using PC-MRI flow in ascending and descending aorta (not achieved in 1 patients). A custom Apple iPhone 5S application was used to obtain carotid pulse waves by holding the camera against the neck. IF parameters of iPhone waveforms (calibrated by cuff brachial pressures) were used in machine learning algorithms (IF-iPhone). The models of TAC and PWV aa were developed using 100 participants (99 for PWV aa ) and blindly tested on an additional 20 individuals. Results: In blind tests, iPhone-IF models showed Pearson correlations of r=0.89 and r=0.84 with the measured values of TAC and PWV aa , respectively (Fig.1). Conclusions: Assessment of PWV aa and TAC can be accurately achieved using an unmodified smartphone (iPhone). PWV aa evaluation with an iPhone can be used to identify, predict, and quantify risk of vascular brain damage. A Noninvasive iPhone-based method can be used in a clinical or home setting to routinely assess TAC in the general population or in HF.

Association of Arterial Stiffness and Atherosclerotic Burden With Brain Structural Changes Among Japanese Men.

Background Little is known regarding whether arterial stiffness and atherosclerotic burden are each independently associated with brain structural changes. Simultaneous assessments of both arterial stiffness and atherosclerotic burden in associations with brain could provide insights into the mechanisms of brain structural changes. Methods and Results Using data from the SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis), we analyzed data among 686 Japanese men (mean [SD] age, 67.9 [8.4] years; range, 46-83 years) free from history of stroke and myocardial infarction. Brachial-ankle pulse wave velocity and coronary artery calcification on computed tomography scans were measured between March 2010 and August 2014. Brain volumes (total brain volume, gray matter, Alzheimer disease signature and prefrontal) and brain vascular damage (white matter hyperintensities) were quantified using brain magnetic resonance imaging from January 2012 through February 2015. In multivariable adjustment models including mean arterial pressure, when brachial-ankle pulse wave velocity and coronary artery calcification were entered into the same models, the β (95% CI) for Alzheimer disease signature volume for each 1-SD increase in brachial-ankle pulse wave velocity was -0.33 (-0.64 to -0.02), and the unstandardized β (95% CI) for white matter hyperintensities for each 1-unit increase in coronary artery calcification was 0.68 (0.05-1.32). Brachial-ankle pulse wave velocity and coronary artery calcification were not statistically significantly associated with total brain and gray matter volumes. Conclusions Among Japanese men, higher arterial stiffness was associated with lower Alzheimer disease signature volumes, whereas higher atherosclerotic burden was associated with brain vascular damage. Arterial stiffness and atherosclerotic burden may be independently associated with brain structural changes via different pathways.

Association between Coffee Consumption and Brain MRI Parameters in the Hamburg City Health Study.

Despite associations of regular coffee consumption with fewer neurodegenerative disorders, its association with microstructural brain alterations is unclear. To address this, we examined the association of coffee consumption with brain MRI parameters representing vascular brain damage, neurodegeneration, and microstructural integrity in 2316 participants in the population-based Hamburg City Health Study. Cortical thickness and white matter hyperintensity (WMH) load were measured on FLAIR and T1-weighted images. Microstructural white matter integrity was quantified as peak width of skeletonized mean diffusivity (PSMD) on diffusion-weighted MRI. Daily coffee consumption was assessed in five groups (<1 cup, 1-2 cups, 3-4 cups, 5-6 cups, >6 cups). In multiple linear regressions, we examined the association between brain MRI parameters and coffee consumption (reference group <1 cup). After adjustment for covariates, 3-4 cups of daily coffee were associated with lower PSMD (p = 0.028) and higher cortical thickness (p = 0.015) compared to <1 cup. Moreover, 1-2 cups per day was also associated with lower PSMD (p = 0.022). Associations with WMH load or other groups of coffee consumption were not significant (p > 0.05). The findings indicate that regular coffee consumption is positively associated with microstructural white matter integrity and cortical thickness. Further research is necessary to determine longitudinal effects of coffee on brain microstructure.

Эффективность и безопасность применения препарата Ренобрейн® СМ у пациентов с хронической ишемией головного мозга

Aim: to study the efficacy and safety of bovine cerebral cortex polypeptides (BCCP) in patients with chronic cerebral ischemia (CCI). Patients and Methods: an open multicenter randomized prospective comparative clinical trial was conducted with the participation of 40 patients with CCI (ICD-10: 167.8) aged 55 to 75 years, having risk factors for cerebrovascular pathology (hypertension, obesity, dyslipidemia or atherosclerosis) and vascular brain damage (according to the data of MRI, the STRIVE v1 protocol). After randomization, main group (n=20) received standard therapy for the underlying disease and Renobrain® СМ 10 mg/day, intramuscularly, for 10 days. Control group (n=20) received only standard therapy of the underlying disease. Clinical and neurological examination was performed using international questionnaires to assess cognitive and functional disorders before and after the therapy course in 30–32 days (Schulte and DSST tests, asthenic state and life quality SF-36 scales). Results: the BCCP, in addition to standard therapy in patients with CCI contributed to a statistically significant (p&lt;0.05) improvement in cognitive functions (volume; refocusing rate; concentration and vigilance; working memory; information processing speed; executive, neurodynamic and regulatory functions), increased exercise tolerance, reduced mental fatigue and improving the life quality. The positive changes that occurred during treatment in the main group were probably related to the GABAergic effect, relationship normalization of the excitatory and inhibitory amino acids and mediators in the central nervous system, which leaded to functional restoration of neuronal cerebral systems. Conclusion: BCCP use in the complex therapy of patients with CCI is pathogenetically justified. Given its neurotrophic effect along with a high safety profile, repeated courses of such a drug and its wider use in patients with vascular brain damage can be recommended. KEYWORDS: chronic cerebral ischemia, cerebrovascular diseases, cognitive disorder, asthenia, bovine cerebral cortex polypeptides. FOR CITATION: Ekusheva E.V., Voitenkov V.B. Efficacy and safety of Renobrain® СМ in patients with chronic cerebral ischemia. Russian Medical Inquiry. 2023;7(10):666–671 (in Russ.). DOI: 10.32364/2587-6821-2023-7-10-9.

Nitro Capsaicin Suppressed Microglial Activation and TNF-α-Induced Brain Microvascular Endothelial Cell Damage.

Chronically activated microglia and brain vascular damage are major causes of neuroinflammation. The aim of this study was to determine the anti-inflammatory effects of nitro capsaicin, a newly modified capsaicin with less irritating characteristics, against microglial activation and brain microvascular endothelial cell damage. Using the SIMA9 microglia cell line, we found that nitro capsaicin reduced nitric oxide (NO) production in LPS-activated microglia better than its parent compound, capsaicin. Nitro capsaicin also decreased the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhanced the levels of anti-inflammatory factors, IL-4 and IL-10, both at the mRNA and protein levels. In the TNF-α-induced vascular damage model, nitro capsaicin decreased expression and secretion of the proinflammatory cytokines IL-1β and IL-6. Phosphorylated NF-κB p65, a key transcription factor that stimulates the signaling of inflammatory pathways, was also reduced in the presence of nitro capsaicin, suggesting that the anti-inflammatory effects of nitro capsaicin were created through reducing NF-κB activation. Together, we concluded that nitro capsaicin has the potential to be further developed as an anti-neuroinflammatory agent.

Association between the frailty index and vascular brain damage: The Treviso Dementia (TREDEM) registry.

An association between frailty and vascular brain damage (VBD) has been described in older adults. However, most studies have identified frailty according to the phenotypic model. It is less clear whether frailty, operationalized as an accumulation of health deficits, is associated with the presence and severity of VBD. The present study was therefore undertaken to verify whether a 50-item frailty index (FI) is related to VBD in a large and relatively unselected cohort of attendees of a memory clinic. The TREDEM (Treviso Dementia) registry includes retrospective observational data of 1584 participants. A modified FI was calculated from 50 variables comprising diseases, disability, behavioral disorders, and blood biochemistry. The presence and severity of VBD, including leukoaraiosis, lacunes, larger infarctions and the hierarchical vascular rating scale (HVRS), were determined based on brain computerized tomography imaging. Multiple logistic regression models were built according to the stepwise method. Mean age of the 1584 participants was 79.6±7.5years and 1033 (65.2%) were females. The average number of health deficits was 11.6±6.2, corresponding to an FI of 0.23±0.12 (range: 0.00-0.56). Each 0.01-point increase in the FI was associated with an increased probability of leukoaraiosis (+2.3%) and severe leukoaraiosis (+5%), lacunas in the basal ganglia (+1.73%), occipital lobes (+2.7%), parietal lobes (+3%), frontal lobes (+3.6%), temporal lobes (+4.2%), and thalamus (+4.4%). Moreover, an increase of 0.01 points in the FI was associated with a 3.1% increase in the probability of HVRS score (≥2). An FI based on routine clinical and laboratory variables was associated with the presence, degree, and some localizations of VBD in a population of older adults with cognitive decline. This frailty assessment tool may therefore be used to identify individuals at risk of developing cerebrovascular disease and, consequently, to implement strategies for vascular risk factor control.

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation. Three hundred ninety patients with a diagnosis of no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia were recruited from the memory clinic. Cerebral microbleeds and lacunes were categorized into strictly lobar, strictly deep, and mixed-location and enlarged perivascular spaces into the centrum semiovale and basal ganglia. Total and region-specific white matter hyperintensity volumes were segmented using FreeSurfer. CBF (n = 333) and the spatial coefficient of variation (n = 390) were analyzed with ExploreASL from 2D-EPI pseudocontinuous arterial spin-labeling images in white matter (WM) and gray matter (GM). To analyze the effect of demographic and vascular risk factors as well as the location and severity of cerebral small-vessel disease markers on arterial spin-labeling parameters, we constructed linear regression models, whereas logistic regression models were used to determine the association between arterial spin-labeling parameters and cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia. Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease, and smoking were associated with lower CBF and a higher spatial coefficient of variation. Higher numbers of lacunes and cerebral microbleeds were associated with lower CBF and a higher spatial coefficient of variation. Location-specific analysis showed mixed-location lacunes and cerebral microbleeds were associated with lower CBF. Higher total, anterior, and posterior white matter hyperintensity volumes were associated with a higher spatial coefficient of variation. No association was observed between enlarged perivascular spaces and arterial spin-labeling parameters. A higher spatial coefficient of variation was associated with the diagnosis of vascular cognitive impairment no dementia, Alzheimer's disease, and vascular dementia. Reduced CBF and an increased spatial coefficient of variation were associated with cerebral small-vessel disease, and more specifically lacunes, whereas cerebral microbleeds and white matter hyperintensities were associated with WM-CBF and GM spatial coefficient of variation. The spatial coefficient of variation was associated with cognitive impairment and dementia, suggesting that hypoperfusion might be the key underlying mechanism for vascular brain damage.

Cognitive resilience depends on white matter connectivity: The Maastricht Study.

Differences in brain network connectivity may reflect the capability of the neurological substrate to compensate for brain damage and preserve cognitive function (cognitive reserve). We examined the associations between white matter connectivity, brain damage markers, and cognition in a population sample of middle-aged individuals. A total of 4759 participants from The Maastricht Study (mean age = 59.2, SD = 8.7, 50.2% male) underwent cognitive testing and diffusion magnetic resonance imaging (dMRI), from which brain volume, structural connectivity, and vascular damage were quantified. Multivariable linear regression was used to investigate whether connectivity modified the association between brain damage and cognition, adjusted for demographic and cardiometabolic risk factors. More atrophic and vascular brain damage was associated with worse cognition scores. Increasing connectivity moderated the negative association between damage and cognition (χ2 = 8.64, df = 3, p ≤ 0.001); individuals with high damage but strong connectivity showed normal cognition. Findings support the reserve hypothesis by showing that brain connectivity is associated with cognitive resilience.

CASE REPORT: HELLP-LIKE SYNDROME IN A 19-YEAR-OLD WOMAN WITH NOT WELL - CONTROLLED HYPERTENSION

Objective: We report a young woman with malignant hypertension (HTN) and multiorgan damage due to microangiopathy. Design and method: A 19-year old woman with previously recognized HTN and family history of HTN developed acute symptoms related to long-standing not well-controlled HTN. The patient presented with high blood pressure (BP), vomiting, epigastric pain, jaundice, impaired consciousness, tonic-clonic seizures, complete left eye blindness and partial right eye blindness. On admission, the patient was conscious but obtunded, with marked cognitive dysfunction, BP 255/143 mm Hg, heart rate 130 bpm, breathing rate 34/min, temperature 36,9C, SpO2 95%. Following admission, a transient loss of consciousness with eyes turning to the left was observed upon sitting up, without any arrhythmia seen in ECG monitoring. Neurological examination was unremarkable. Fundoscopy showed grade IV changes with papilledema, numerous hemorrhages and cotton wool spots. Results: Pregnancy test was negative. Laboratory test abnormalities included macrocytic anemia (Hb 10.25 g/dL, Hct 33.6%, MCV 103 fL), elevated leukocyte count (17.1x10 3 /L), low platelet count (69x10 3 /L), elevated serum bilirubin (10.4 mg/dL) and creatinine (4.2 mg/dL), and slightly elevated AspAT and troponin I. Brain CT showed chronic vascular brain damage. BP was gradually normalized using intravenous/oral antihypertensive drugs. Clinical symptoms and laboratory abnormalities resolved, except for left eye blindness and serum creatinine (2.47 mg/dL at discharge). Secondary HTN was excluded. The final diagnosis was malignant HTN, acute hypertensive encephalopathy with seizures, acute liver damage, chronic kidney disease, acute hemolytic anemia due to hypertensive microangiopathy, and permanent left eye blindness. Due to hemolysis and low platelet count, differential diagnosis included hemolytic-uremic syndrome which was excluded. The clinical presentation resembled that of HELLP syndrome in pregnant women with eclampsia, with evidence of target organ damage, low platelet count, liver and kidney dysfunction, and hemolytic jaundice. Conclusions: Young patients with essential HTN rarely present with such fulminant malignant HTN manifesting with neurological symptoms, with evidence of multiorgan damage due to microangiopathy. Similarly, microangiopathic hemolytic anemia rarely complicates malignant HTN. Initial clinical presentation was challenging due to neurological symptoms and evidence of multiorgan failure.