Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke.

The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.

Quantitative brain [F]FDG PET beyond normal blood glucose levels.

Introduction SUV measurements from static brain [F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL.

Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke.

Background: Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking.

Methods: A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls).

PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review.

Background: Monogenic Alzheimer's disease (AD) has severe health and socioeconomic repercussions. Its rarest cause is presenilin 2 () gene mutations. We present two new cases with presumed PSEN2-AD with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients.

Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke.

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging).

Differential blood-based biomarkers of subcortical and deep brain small vessel disease.

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies.

Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter.

dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe.

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA-directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines.

Neuroprotection Afforded by an Enriched Mediterranean-like Diet Is Modified by Exercise in a Rat Male Model of Cerebral Ischemia.

Ischemic stroke is an important cause of mortality and disability worldwide. Given that current treatments do not allow a remarkably better outcome in patients after stroke, it is mandatory to seek new approaches to preventing stroke and/or complementing the current treatments or ameliorating the ischemic insult. Multiple preclinical and clinical studies highlighted the potential beneficial roles of exercise and a Mediterranean diet following a stroke.

Partial volume correction in longitudinal tau PET studies: is it really needed?

Background: [F]flortaucipir (FTP) tau PET quantification is known to be affected by non-specific binding in off-target regions. Although partial volume correction (PVC) techniques partially account for this effect, their inclusion may also introduce noise and variability into the quantification process. While the impact of these effects has been studied in cross-sectional designs, the benefits and drawbacks of PVC on longitudinal FTP studies is still under scrutiny.

Systemic biomarker associated with poor outcome after futile reperfusion.

Background: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon.

Small extracellular vesicles administered directly in the brain promote neuroprotection and decreased microglia reactivity in a stroke mouse model.

Herein, we investigate the bioactivity of small extracellular vesicles (sEVs), focusing on their local effect in the brain. sEVs from mononuclear cells (MNCs) showed superior effects to sEVs from mesenchymal stem cells (MSCs) and were able to promote neuroprotection and decrease microglia reactivity in a stroke mouse model.

Magnetic separation and concentration of Aβ 1-42 molecules dispersed at the threshold concentration for Alzheimer's disease diagnosis in clinically-relevant volumes of sample.

Background: Alzheimer's disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. The progressive aging of the population is expected to exacerbate this problem in the next decades. Therefore, there is an urgent need to develop quantitative diagnostic methodologies to assess the onset the disease and its progression especially in the initial phases.

Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer's disease to this relationship.

Aim: To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease.

Materials And Methods: Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis.

Organotypic Hippocampal Slice Cultures from Adult Tauopathy Mice and Theragnostic Evaluation of Nanomaterial Phospho-TAU Antibody-Conjugates.

Organotypic slice culture models surpass conventional in vitro methods in many aspects. They retain all tissue-resident cell types and tissue hierarchy. For studying multifactorial neurodegenerative diseases such as tauopathies, it is crucial to maintain cellular crosstalk in an accessible model system.

Periodontal inflammation is associated with increased circulating levels of endothelial progenitor cells: a retrospective cohort study in a high vascular risk population.

Background: One of the main biological mechanisms behind the link between periodontitis and atherosclerotic vascular diseases is vascular endothelial dysfunction. Particularly, circulating endothelial progenitor cells (EPCs) have been considered a biomarker of altered vascular endothelial function.

Objectives: The aim of this study was to investigate relationship between periodontal inflammation and increased number of circulating EPCs.

Periodontitis is associated with subclinical cerebral and carotid atherosclerosis in hypertensive patients: A cross-sectional study.

Objective: To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored.

Material And Methods: This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)].

Biomarkers Assessing Endothelial Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common degenerative disorder in the elderly in developed countries. Currently, growing evidence is pointing at endothelial dysfunction as a key player in the cognitive decline course of AD. As a main component of the blood-brain barrier (BBB), the dysfunction of endothelial cells driven by vascular risk factors associated with AD allows the passage of toxic substances to the cerebral parenchyma, producing chronic hypoperfusion that eventually causes an inflammatory and neurotoxic response.

Influence of Temperature Chronobiology on Stroke Outcome.

The circadian system regulates numerous physiological variables, including body temperature. Additionally, a circadian patter has been described in stroke onset. Considering this, we hypothesised that the chronobiology of temperature may have an impact on stroke onset and functional outcomes.

Engineering graphene-based electrodes for optical neural stimulation.

Graphene-based materials (GBMs) have been investigated in recent years with the aim of developing flexible interfaces to address a range of neurological disorders, where electrical stimulation may improve brain function and tissue regeneration. The recent discovery that GBM electrodes can generate an electrical response upon light exposure has inspired the development of non-genetic approaches capable of selectively modulating brain cells without genetic manipulation (, optogenetics). Here, we propose the conjugation of graphene with upconversion nanoparticles (UCNPs), which enable wireless transcranial activation using tissue-penetrating near-infrared (NIR) radiation.

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.

Immunomodulatory Effect of Human Lactoferrin on Toll-like Receptors 2 Expression as Therapeutic Approach for Keratoconus.

Keratoconus (KC) is a corneal disorder whose etiology shares a close relationship with Lactoferrin (LTF) dysregulation and Toll-like Receptors 2 (TLR2) overexpression. This study shows how these two important biomarkers are clinically and molecularly interrelated, increasing knowledge about KC pathophysiology, and opening the door to future therapies. In this prospective clinical study, serum and tear LTF concentrations were quantified in 90 KC patients and 60 controls.