Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France.

This geoepidemiological study, performed in Italy and France, shows that Erdheim-Chester disease is increasingly diagnosed and cases cluster in specific geographic areas, namely southern Italy and central France. Disease frequency inversely correlates with the Human Development Index.

Derivation and validation of a predictive mortality model of in-hospital patients with Acinetobacter baumannii nosocomial infection or colonization.

PURPOSE: Acinetobacter baumannii (Ab) is a Gram-negative opportunistic bacterium responsible for nosocomial infections or colonizations. It is considered one of the most alarming pathogens due to its multi-drug resistance and due to its mortality rate, ranging from 34 to 44,5% of hospitalized patients. The aim of the work is to create a predictive mortality model for hospitalized patient with Ab infection or colonization. METHODS: A cohort of 140 sequentially hospitalized patients were randomized into a training cohort (TC) (100 patients) and a validation cohort (VC) (40 patients). Statistical bivariate analysis was performed to identify variables discriminating surviving patients from deceased ones in the TC, considering both admission time (T0) and infection detection time (T1) parameters. A custom logistic regression model was created and compared with models obtained from the "status" variable alone (Ab colonization/infection), SAPS II, and APACHE II scores. ROC curves were built to identify the best cut-off for each model. RESULTS: Ab infection status, use of penicillin within 90 days prior to ward admission, acidosis, Glasgow Coma Scale, blood pressure, hemoglobin and use of NIV entered the logistic regression model. Our model was confirmed to have a better sensitivity (63%), specificity (85%) and accuracy (80%) than the other models. CONCLUSION: Our predictive mortality model demonstrated to be a reliable and feasible model to predict mortality in Ab infected/colonized hospitalized patients.

The Mediterranean Diet, Its Microbiome Connections, and Cardiovascular Health: A Narrative Review.

The Mediterranean diet (MD), rich in minimally processed plant foods and in monounsaturated fats but low in saturated fats, meat, and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratios, lipids, and inflammation markers, and even prevents the development of fatal and nonfatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns over its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides, and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbiota.

Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes: Background and Therapeutic Approaches.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischemia. ncRNAs, particularly microRNAs, and long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of ischemic stroke secondary to large-artery atherosclerosis. In macroscopic evaluation, vulnerable plaques are characterized by one or more of the following features: microcalcification; neovascularization; lipid-rich necrotic cores (LRNCs); intraplaque hemorrhage (IPH); thin fibrous caps; plaque surface ulceration; huge dimensions, suggesting stenosis; and plaque rupture. Recognizing these macroscopic characteristics is crucial for estimating the risk of cerebrovascular events, also in the case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that are scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talk governing plaque inflammation, rupture potential, and thrombogenicity. The current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehensive analysis of the current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional attributes that characterize vulnerable plaques.

Metabolic memory in diabetic foot syndrome (DFS): MICRO-RNAS, single nucleotide polymorphisms (SNPs) frequency and their relationship with indices of endothelial function and adipo-inflammatory dysfunction.

BACKGROUND: Diabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximately twice that of patients without foot ulcers. "Metabolic memory" represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing. METHODS: The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigenetic changes on miRNA 126, 305, and 217 expression and the frequency of the SNPs of genes encoding inflammatory molecules (e.g., IL-6 and TNF-alpha) and their correlations with serum levels of proangiogenic molecules (e.g., ENOS, VEGF and HIF-1alpha) and several adipokines as well as with endothelial dysfunction, assessed noninvasively by reactive hyperaemia peripheral artery tonometry. Between March 2021 and June 2022, 110 patients were enrolled into the study: 50 diabetic patients with diabetic foot injuries, 40 diabetic patients without ulcerative complications and 20 nondiabetic patients as the control group. RESULTS: Diabetic subjects with lower limb ulcerative lesions exhibited higher levels of inflammatory cytokines, such as VEGF (191.40 ± 200 pg/mL vs. 98.27 ± 56.92 pg/mL vs. 71.01 ± 52.96 pg/mL; p = 0.22), HIF-1alpha (40.18 ± 10.80 ng/mL vs. 33.50 ± 6.16 ng/mL vs. 33.85 ± 6.84 ng/mL; p = 0.10), and Gremlin-1 (1.72 ± 0.512 ng/mL vs. 1.31 ± 0.21 ng/mL vs. 1.11 ± 0.19 ng/mL; p < 0.0005), than those without lower limb ulcers and healthy controls. Furthermore, we observed that miR-217-5p and miR-503-5p were 2.19-fold (p < 0.05) and 6.21-fold (p = 0.001) more highly expressed in diabetic foot patients than in healthy controls, respectively. Additionally, diabetic patients without lower limb ulcerative complications showed 2.41-fold (p = 0) and 2.24-fold (p = 0.029) higher expression of miR-217-5p and miR-503-5p, respectively, than healthy controls. Finally, diabetic patients with and without ulcerative complications of the lower limbs showed higher expression of the VEGFC2578A CC polymorphism (p = 0.001) and lower expression of the VEGFC2578A AC polymorphism (p < 0.005) than the healthy control population. We observed a significant increase in Gremlin-1 levels in patients with diabetic foot, suggesting that this inflammatory adipokine may serve as a predictive marker for the diagnosis of diabetic foot. CONCLUSIONS: Our results highlighted that patients with diabetic foot showed predominant expression of the VEGF C2578A CC polymorphism and reduced expression of the AC allele. Additionally, we found an overexpression of miR-217-5p and miR-503-5p in diabetic patients with and without diabetic foot syndrome compared with healthy controls. These results align with those reported in the literature, in which the overexpression of miR-217-5p and miR-503-5p in the context of diabetic foot is reported. The identification of these epigenetic modifications could therefore be helpful in the early diagnosis of diabetic foot and the treatment of risk factors. However, further studies are necessary to confirm this hypothesis.

Role of Mediterranean diet in the development and recurrence of meningiomas: a narrative review.

Several studies through the years have proven how an unhealthy nutrition, physical inactivity, sedentary lifestyle, obesity, and smoking represent relevant risk factors in cancer genesis. This study aims to provide an overview about the relationship between meningiomas and food assumption in the Mediterranean diet and whether it can be useful in meningioma prevention or it, somehow, can prevent their recurrence. The authors performed a wide literature search in PubMed and Scopus databases investigating the presence of a correlation between Mediterranean diet and meningiomas. The following MeSH and free text terms were used: "Meningiomas" AND "Diet" and "Brain tumors" AND "diet." Databases' search yielded a total of 749 articles. After duplicate removal, an abstract screening according to the eligibility criteria has been performed and 40 articles were selected. Thirty-one articles were excluded because they do not meet the inclusion criteria. Finally, a total of 9 articles were included in this review. It is widely established the key and protective role that a healthy lifestyle and a balanced diet can have against tumorigenesis. Nevertheless, studies focusing exclusively on the Mediterranean diet are still lacking. Thus, multicentric and/or prospective, randomized studies are mandatory to better assess and determine the impact of food assumptions in meningioma involvement.

Immunoinflammatory Background of Neuronal Damage in Stroke.

Ischemic stroke is caused by a reduction in blood flow to the brain and is a major cause of mortality and disability worldwide [...].

Molecular Research on Migraine: From Pathogenesis to Treatment.

Migraine is a common, multifactorial, disabling, recurrent, hereditary, neurovascular headache disorder [...].

The Natriuretic Peptide System: A Single Entity, Pleiotropic Effects.

In the modern scientific landscape, natriuretic peptides are a complex and interesting network of molecules playing pleiotropic effects on many organs and tissues, ensuring the maintenance of homeostasis mainly in the cardiovascular system and regulating the water-salt balance. The characterization of their receptors, the understanding of the molecular mechanisms through which they exert their action, and the discovery of new peptides in the last period have made it possible to increasingly feature the physiological and pathophysiological role of the members of this family, also allowing to hypothesize the possible settings for using these molecules for therapeutic purposes. This literature review traces the history of the discovery and characterization of the key players among the natriuretic peptides, the scientific trials performed to ascertain their physiological role, and the applications of this knowledge in the clinical field, leaving a glimpse of new and exciting possibilities for their use in the treatment of diseases.

Atherosclerosis and Its Related Laboratory Biomarkers.

Atherosclerosis constitutes a persistent inflammatory ailment, serving as the predominant underlying condition for coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease. The progressive buildup of plaques within the walls of medium- and large-caliber arteries characterizes the atherosclerotic process. This accumulation results in significant narrowing that impedes blood flow, leading to critical tissue oxygen deficiency. Spontaneous blockage of thrombotic vessels can precipitate stroke and myocardial infarction, which are complications representing the primary global causes of mortality. Present-day models for predicting cardiovascular risk incorporate conventional risk factors to gauge the likelihood of cardiovascular events over a ten-year span. In recent times, researchers have identified serum biomarkers associated with an elevated risk of atherosclerotic events. Many of these biomarkers, whether used individually or in combination, have been integrated into risk prediction models to assess whether their inclusion enhances predictive accuracy. In this review, we have conducted a comprehensive analysis of the most recently published literature concerning serum biomarkers associated with atherosclerosis. We have explored the potential utility of incorporating these markers in guiding clinical decisions.

The Role of Biomarkers, Metabolomics, and COVID-19 in Venous Thromboembolism-A Review of Literature.

In recent years, the field of venous thromboembolism has undergone numerous innovations, starting from the recent discoveries on the role of biomarkers, passing through the role of metabolomics in expanding our knowledge on pathogenic mechanisms, which have opened up new therapeutic targets. A variety of studies have contributed to characterizing the metabolic phenotype that occurs in venous thromboembolism, identifying numerous pathways that are altered in this setting. Among these pathways are the metabolism of carnitine, tryptophan, purine, and fatty acids. Furthermore, new evidence has emerged with the recent COVID-19 pandemic. Hypercoagulability phenomena induced by this viral infection appear to be related to altered von Willebrand factor activity, alteration of the renin-angiotensin-aldosterone system, and dysregulation of both innate and adaptive immunity. This is the first literature review that brings together the most recent evidence regarding biomarkers, metabolomics, and COVID-19 in the field of venous thromboembolism, while also mentioning current therapeutic protocols.

Molecular Pathogenesis of Central and Peripheral Nervous System Complications in Anderson-Fabry Disease.

Fabry disease (FD) is a recessive monogenic disease linked to chromosome X due to more than two hundred mutations in the alfa-galactosidase A (GLA) gene. Modifications of the GLA gene may cause the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriasylsphingosine (lyso-Gb3), in lysosomes of several types of cells of the heart, kidneys, skin, eyes, peripheral and central nervous system (not clearly and fully demonstrated), and gut with different and pleiotropic clinical symptoms. Among the main symptoms are acroparesthesias and pain crisis (involving the peripheral nervous system), hypohidrosis, abdominal pain, gut motility abnormalities (involving the autonomic system), and finally, cerebrovascular ischemic events due to macrovascular involvement (TIA and stroke) and lacunar strokes and white matter abnormalities due to a small vessel disease (SVS). Gb3 lysosomal accumulation causes cytoplasmatic disruption and subsequent cell death. Additional consequences of Gb3 deposits are inflammatory processes, abnormalities of leukocyte function, and impaired trafficking of some types of immune cells, including lymphocytes, monocytes, CD8+ cells, B cells, and dendritic cells. The involvement of inflammation in AFD pathogenesis conflicts with the reported poor correlation between CRP levels as an inflammation marker and clinical scores such as the Mainz Severity Score Index (MSSI). Also, some authors have suggested an autoimmune reaction is involved in the disease's pathogenetic mechanism after the α-galactosidase A deficiency. Some studies have reported a high degree of neuronal apoptosis inhibiting protein as a critical anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Notably, this apoptotic upregulation did not change after treatment with enzymatic replacement therapy (ERT), with a further upregulation of the apoptosis-inducing factor after ERT started. Gb3-accumulation has been reported to increase the degree of oxidative stress indexes and the production of reactive oxygen species (ROS). Lipids and proteins have been reported as oxidized and not functioning. Thus, neurological complications are linked to different pathogenetic molecular mechanisms. Progressive accumulation of Gb3 represents a possible pathogenetic event of peripheral nerve involvement. In contrast, central nervous system participation in the clinical setting of cerebrovascular ischemic events seems to be due to the epitheliopathy of Anderson-Fabry disease with lacunar lesions and white matter hyperintensities (WMHs). In this review manuscript, we revised molecular mechanisms of peripheral and central neurological complications of Anderson-Fabry Disease. The management of Fabry disease may be improved by the identification of biomarkers that reflect the clinical course, severity, and progression of the disease. Intensive research on biomarkers has been conducted over the years to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. Recent proteomic or metabolomic studies are in progress, investigating plasma proteome profiles in Fabry patients: these assessments may be useful to characterize the molecular pathology of the disease, improve the diagnostic process, and monitor the response to treatment.

New Insights on Metabolic and Genetic Basis of Migraine: Novel Impact on Management and Therapeutical Approach.

Migraine is a hereditary disease, usually one-sided, sometimes bilateral. It is characterized by moderate to severe pain, which worsens with physical activity and may be associated with nausea and vomiting, may be accompanied by photophobia and phonophobia. The disorder can occur at any time of the day and can last from 4 to 72 h, with and without aura. The pathogenic mechanism is unclear, but extensive preclinical and clinical studies are ongoing. According to electrophysiology and imaging studies, many brain areas are involved, such as cerebral cortex, thalamus, hypothalamus, and brainstem. The activation of the trigeminovascular system has a key role in the headache phase. There also appears to be a genetic basis behind the development of migraine. Numerous alterations have been identified, and in addition to the genetic cause, there is also a close association with the surrounding environment, as if on the one hand, the genetic alterations may be responsible for the onset of migraine, on the other, the environmental factors seem to be more strongly associated with exacerbations. This review is an analysis of neurophysiological mechanisms, neuropeptide activity, and genetic alterations that play a fundamental role in choosing the best therapeutic strategy. To date, the goal is to create a therapy that is as personalized as possible, and for this reason, steps forward have been made in the pharmacological field in order to identify new therapeutic strategies for both acute treatment and prophylaxis.

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases.

Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.

The Role of Immunosenescence in Cerebral Small Vessel Disease: A Review.

Cerebral small vessel disease (CSVD) is one of the most important causes of vascular dementia. Immunosenescence and inflammatory response, with the involvement of the cerebrovascular system, constitute the basis of this disease. Immunosenescence identifies a condition of deterioration of the immune organs and consequent dysregulation of the immune response caused by cellular senescence, which exposes older adults to a greater vulnerability. A low-grade chronic inflammation status also accompanies it without overt infections, an "inflammaging" condition. The correlation between immunosenescence and inflammaging is fundamental in understanding the pathogenesis of age-related CSVD (ArCSVD). The production of inflammatory mediators caused by inflammaging promotes cellular senescence and the decrease of the adaptive immune response. Vice versa, the depletion of the adaptive immune mechanisms favours the stimulation of the innate immune system and the production of inflammatory mediators leading to inflammaging. Furthermore, endothelial dysfunction, chronic inflammation promoted by senescent innate immune cells, oxidative stress and impairment of microglia functions constitute, therefore, the framework within which small vessel disease develops: it is a concatenation of molecular events that promotes the decline of the central nervous system and cognitive functions slowly and progressively. Because the causative molecular mechanisms have not yet been fully elucidated, the road of scientific research is stretched in this direction, seeking to discover other aberrant processes and ensure therapeutic tools able to enhance the life expectancy of people affected by ArCSVD. Although the concept of CSVD is broader, this manuscript focuses on describing the neurobiological basis and immune system alterations behind cerebral aging. Furthermore, the purpose of our work is to detect patients with CSVD at an early stage, through the evaluation of precocious MRI changes and serum markers of inflammation, to treat untimely risk factors that influence the burden and the worsening of the cerebral disease.

The Role of the Coagulation System in Peripheral Arterial Disease: Interactions with the Arterial Wall and Its Vascular Microenvironment and Implications for Rational Therapies.

Peripheral artery disease (PAD) is a clinical manifestation of atherosclerotic disease with a large-scale impact on the economy and global health. Despite the role played by platelets in the process of atherogenesis being well recognized, evidence has been increasing on the contribution of the coagulation system to the atherosclerosis formation and PAD development, with important repercussions for the therapeutic approach. Histopathological analysis and some clinical studies conducted on atherosclerotic plaques testify to the existence of different types of plaques. Likely, the role of coagulation in each specific type of plaque can be an important determinant in the histopathological composition of atherosclerosis and in its future stability. In this review, we analyze the molecular contribution of inflammation and the coagulation system on PAD pathogenesis, focusing on molecular similarities and differences between atherogenesis in PAD and coronary artery disease (CAD) and discussing the possible implications for current therapeutic strategies and future perspectives accounting for molecular inflammatory and coagulation targets. Understanding the role of cross-talking between coagulation and inflammation in atherosclerosis genesis and progression could help in choosing the right patients for future dual pathway inhibition strategies, where an antiplatelet agent is combined with an anticoagulant, whose role, despite pathophysiological premises and trials' results, is still under debate.

Olive Oil in the Mediterranean Diet and Its Biochemical and Molecular Effects on Cardiovascular Health through an Analysis of Genetics and Epigenetics.

Human nutrition is a relatively new science based on biochemistry and the effects of food constituents. Ancient medicine considered many foods as remedies for physical performance or the treatment of diseases and, since ancient times, especially Greek, Asian and pre-Christian cultures similarly thought that they had beneficial effects on health, while others believed some foods were capable of causing illness. Hippocrates described the food as a form of medicine and stated that a balanced diet could help individuals stay healthy. Understanding molecular nutrition, the interaction between nutrients and DNA, and obtaining specific biomarkers could help formulate a diet in which food is not only a food but also a drug. Therefore, this study aims to analyze the role of the Mediterranean diet and olive oil on cardiovascular risk and to identify their influence from the genetic and epigenetic point of view to understand their possible protective effects.

Diabetes and Ischemic Stroke: An Old and New Relationship an Overview of the Close Interaction between These Diseases.

Diabetes mellitus is a comprehensive expression to identify a condition of chronic hyperglycemia whose causes derive from different metabolic disorders characterized by altered insulin secretion or faulty insulin effect on its targets or often both mechanisms. Diabetes and atherosclerosis are, from the point of view of cardio- and cerebrovascular risk, two complementary diseases. Beyond shared aspects such as inflammation and oxidative stress, there are multiple molecular mechanisms by which they feed off each other: chronic hyperglycemia and advanced glycosylation end-products (AGE) promote 'accelerated atherosclerosis' through the induction of endothelial damage and cellular dysfunction. These diseases impact the vascular system and, therefore, the risk of developing cardio- and cerebrovascular events is now evident, but the observation of this significant correlation has its roots in past decades. Cerebrovascular complications make diabetic patients 2-6 times more susceptible to a stroke event and this risk is magnified in younger individuals and in patients with hypertension and complications in other vascular beds. In addition, when patients with diabetes and hyperglycemia experience an acute ischemic stroke, they are more likely to die or be severely disabled and less likely to benefit from the one FDA-approved therapy, intravenous tissue plasminogen activator. Experimental stroke models have revealed that chronic hyperglycemia leads to deficits in cerebrovascular structure and function that may explain some of the clinical observations. Increased edema, neovascularization, and protease expression as well as altered vascular reactivity and tone may be involved and point to potential therapeutic targets. Further study is needed to fully understand this complex disease state and the breadth of its manifestation in the cerebrovasculature.

Pathogenetic Mechanisms of Hypertension-Brain-Induced Complications: Focus on Molecular Mediators.

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.