Molecular and Functional Alterations in the Cerebral Microvasculature in an Optimized Mouse Model of Sepsis-Associated Cognitive Dysfunction.

Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical studies indicate an association between sepsis, endothelial dysfunction, and cognitive decline. However, the investigations of the role and therapeutic potential of the cerebral microvasculature in sepsis-induced cognitive dysfunction have been limited by the lack of standardized experimental models for evaluating the alterations in the cerebral microvasculature and cognition induced by the systemic inflammatory response.

Molecular and functional alterations in the cerebral microvasculature in an optimized mouse model of sepsis-associated cognitive dysfunction.

Unlabelled: Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical studies indicate an association between sepsis, endothelial dysfunction, and cognitive decline. However, the investigations of the role and therapeutic potential of the cerebral microvasculature in systemic inflammation-induced cognitive dysfunction have been limited by the lack of standardized experimental models for evaluating the alterations in the cerebral microvasculature and cognition induced by the systemic inflammatory response.

Fibrin-Targeted Nanoparticles for Finding, Visualizing and Characterizing Blood Clots in Acute Ischemic Stroke.

Recanalization of the occluded artery is the gold standard treatment for acute ischemic stroke, which includes enzymatic fibrinolytic treatment with the use of recombinant tissue plasminogen activators (rtPAs) to disrupt the occluding clot, the use of mechanical thrombectomy to physically remove the clot, or a combination of both. Fibrin is one of the main components of blood clots causing ischemic stroke and is the target of rtPA upon activation of plasminogen in the clot. In addition, fibrin content also influences the efficacy of mechanical thrombectomy.

Antihyperthermic Treatment in the Management of Malignant Infarction of the Middle Cerebral Artery.

Malignant infarction of the middle cerebral artery (m-MCA) is a complication of ischemic stroke. Since hyperthermia is a predictor of poor outcome, and antihyperthermic treatment is well tolerated, our main aim was to analyze whether the systemic temperature decrease within the first 24 h was associated with a better outcome. Furthermore, we studied potential biochemical and neuroimaging biomarkers.

Associations between RNA-Binding Motif Protein 3, Fibroblast Growth Factor 21, and Clinical Outcome in Patients with Stroke.

Background: RNA-binding motif protein 3 (RBM3) is a cold-induced marker of good functional outcome of ischemic stroke that is promising as a protective target. Fibroblast growth factor 21 (FGF21) is an obesity- and temperature-related hormone that upregulates the expression of RBM3, which is beneficial as a recombinant treatment and has been tested under different experimental pathological conditions, including stroke. However, the interaction between RBM3 and FGF21 has not yet been tested for clinical stroke conditions.

sTWEAK is a leukoaraiosis biomarker associated with neurovascular angiopathy.

Objective: Leukoaraiosis (LA) refers to white matter lesions of undetermined etiology associated with the appearance and worsening of vascular pathologies. The aim is to confirm an increased frequency and intensity of LA in symptomatic patients with neurovascular pathology compared with asymptomatic subjects, and its association with circulating serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK).

Methods: An observational study was conducted in which two groups of patients were compared.

Tear Proteomics in Keratoconus: A Quantitative SWATH-MS Analysis.

Purpose: To elucidate dysregulated proteins in keratoconus (KC) to provide a better understanding of the molecular mechanisms that lead to the development of the disease using sequential window acquisition of all theoretical mass spectra (SWATH-MS) as a protein quantification tool of the tear proteomic profile.

Methods: Prospective cross-sectional study that includes 25 keratoconic eyes and 25 healthy eyes. All participants underwent a clinical, tomographic, and aberrometric exam.

Characterization of a Temporal Profile of Biomarkers as an Index for Ischemic Stroke Onset Definition.

Background And Purpose: Stroke is a dynamic process in terms of molecular mechanisms, with prominent glutamate-mediated excitotoxicity at the onset of symptoms followed by IL-6-mediated inflammation. Our aim was to study a serum glutamate/IL-6 ratio as an index for stroke onset definition.

Methods: A total of 4408 ischemic stroke patients were recruited and then subdivided into four quartiles according to latency time in minutes (0-121, 121-185, 185-277 and >277).

Neurological Instability in Ischemic Stroke: Relation with Outcome, Latency Time, and Molecular Markers.

The National Institutes of Health Stroke Scale (NIHSS) is commonly used to evaluate stroke neurological deficits and to predict the patient's outcome. Neurological instability (NI), defined as the variation of the NIHSS in the first 48 h, is a simple clinical metric that reflects dynamic changes in the area of the brain affected by the ischemia. We hypothesize that NI may represent areas of cerebral instability known as penumbra, which could expand or reduce brain injury and its associated neurological sequels.

sTWEAK is a marker of early haematoma growth and leukoaraiosis in intracerebral haemorrhage.

Objective: To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis (LA) and the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in patients with intracerebral haemorrhage (ICH).

Methods: This is a retrospective observational study of patients with nontraumatic ICH. Clinical and biochemical parameters were analysed.

Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome.

RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-binding motif protein 3 was investigated in ischaemic animal models subjected to systemic and focal brain hypothermia, specifically the effects of RNA-binding motif protein 3 silencing and overexpression on ischaemic lesions.

Mild systemic inflammation enhances response to OnabotulinumtoxinA in chronic migraineurs.

The anti-inflammatory effect of OnabotulinumtoxinA (OnabotA) has been a matter of discussion for many years. In chronic migraine, however, increased pro-inflammatory state is associated with good response to OnabotA. We aimed to investigate whether a mild systemic inflammatory state elicited by a common oral infection (periodontitis) could enhance treatment response to OnabotA.

The presence of leukoaraiosis enhances the association between sTWEAK and hemorrhagic transformation.

Objective: To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor-like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies.

Methods: This is a retrospective observational study. The primary endpoint was to study the sTWEAK-LA-HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3-months.

Temperature-Induced Changes in Reperfused Stroke: Inflammatory and Thrombolytic Biomarkers.

Although hyperthermia is associated with poor outcomes in ischaemic stroke (IS), some studies indicate that high body temperature may benefit reperfusion therapies. We assessed the association of temperature with effective reperfusion (defined as a reduction of ≥8 points in the National Institute of Health Stroke Scale (NIHSS) within the first 24 h) and poor outcome (modified Rankin Scale (mRS) > 2) in 875 retrospectively-included IS patients. We also studied the influence of temperature on thrombolytic (cellular fibronectin (cFn); matrix metalloproteinase 9 (MMP-9)) and inflammatory biomarkers (tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6)) and their relationship with effective reperfusion.

Antihyperthermic treatment decreases perihematomal hypodensity.

Objective: To investigate the effect on perihematomal hypodensity and outcome of a decrease in body temperature in the first 24 hours in patients with intracerebral hemorrhage (ICH).

Methods: In this retrospective study on a prospectively registered database, among the 1,100 patients, 795 met all the inclusion criteria. Temperature variations in the first 24 hours and perihematomal hypodensity (PHHD) were recorded.

Severe periodontitis is linked with increased peripheral levels of sTWEAK and PTX3 in chronic migraineurs.

Objectives: Periodontitis (PD) and chronic migraine (CM) have been recently linked, and inflammatory processes and vascular endothelial changes are hypothesized as potential mediators of this relationship. The aim of this cross-sectional analysis was to investigate the potential association of PD with vascular systemic inflammation and complement activation in patients with CM.

Materials And Methods: Ninety-four chronic migraineurs underwent a full-mouth periodontal evaluation and a measure of PD activity and severity, namely the periodontal inflamed surface area (PISA) was calculated for each patient.

Periodontal inflammation is related to increased serum calcitonin gene-related peptide levels in patients with chronic migraine.

Background: Recently, a relationship was found between periodontitis and chronic migraine. Calcitonin gene-related peptide (CGRP) is a key element in migraine pathophysiology. However, no information exists of the potential association between periodontal inflammation and CGRP in chronic migraine.

Blood glutamate EAAT-cell grabbing therapy in cerebral ischemia.

Background: Excitatory amino acid transporter 2 (EAAT) plays a pivotal role in glutamate clearance in the adult brain, thereby preventing excitotoxic effects. Considering the high efficacy of EAAT for glutamate uptake, we hypothesized that the expression of this transporter in mesenchymal stem cells (MSCs) for systemic administration could yield a cell-based glutamate-grabbing therapy, combining the intrinsic properties of these cells with excitotoxic protection.

Methods: To address this hypothesis, EAAT-encoding cDNA was introduced into MSCs and human embryonic kidney 293 cells (HEK cells) as the control cell line.

Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain Natriuretic Peptide.

Background: Besides the relevant role of brain-type natriuretic peptide (BNP) as biomarker of cardioembolic strokes, new experimental evidences suggest that this peptide may mediate neuroprotective effects. In this study, we have evaluated for the first time the clinical association between BNP (by means of proBNP) and good outcome in ischemic stroke patients, and analyzed the effect of blood BNP increase in an ischemic animal model.

Methods And Results: A retrospective study with 2 different cohorts (262 patients in cohort I and 610 in cohort II) from the same prospective stroke registry was performed.