Astroglial phenotypes in traumatic brain injury and their relationship with neuronal degeneration

Astrocytes are key players in the Central Nervous System injury.By not completely defined pathways, reactive astrocytes may suffer a pathological remodeling engaging a pro-inflammatory phenotype that is very stable and promote further neuroinflammation andneurodegeneration. We here aimed to define the spatio-temporaldistribution of astroglial phenotypes after traumatic brain injury andthe consequences for neuronal survival and behavioral parameters.Following a stereotaxic stab wound injury (0.8 mm needle, coordinates 2 mm posterior and lateral to Bregma; 1 mm depth) performedin C57BL/6 mice and immunohistochemistry on brain sections, weclassified GFAP reactive astrocytes in five different phenotypes defined using Sholl analysis (Auzmendi et al., Molec. Neurobiol. 2019).While at 1 day post-injury (DPI) GFAP+ astrocytes were not differentfrom contralateral non-injured hemisphere, at 3DPI and 7DPI highly reactive phenotypes colocalized with altered neurons in lesionpenumbra. At 14DPI highly reactive astrocytes and altered neuronswere abundant only in the lesion core. Pro-inflammatory gain offunction paradigm was achieved by administering LPS (5 mg/Kg i.p)in lesioned animals, and that resulted in a greater number of complex reactive astrocytes at 7DPI (p<0.05) and a population of C3+astrocytes. On the other hand, loss of function paradigm with chemical NFkB blocker sulfasalazine (150 mg/kg i.p) significantly reducedhighly reactive astrocytes (p<0.05) and showed reduced neuronaldeath. Animal motor deficits were analyzed by computer-assistedopen field, but at 7DPI we were unable to detect significative differences among groups probably due to the small lesion size. Weconclude that increased GFAP+ higher complexity astrocytes areassociated with increased neuronal death and that NFkB pathway islikely to be involved in the pathological conversion to the pro-inflammatory-neurodegenerative phenotype.Fil: Cieri, M. B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Mailing, Ingrid Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaLXV Reunión anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Fisiologí

First records of the iceryine scale insects \u3ci\u3eCrypticerya brasiliensis\u3c/i\u3e (Hempel) and \u3ci\u3eCrypticerya genistae\u3c/i\u3e (Hempel) (Hemiptera: Monophlebidae) for Colombia

Abstract. Crypticerya brasiliensis (Hempel) and Crypticerya genistae (Hempel) (Hemiptera: Monophlebidae: Iceryini) are herein reported for the fi rst time in Colombia. The above two species and Crypticerya multicicatrices Kondo and Unruh and Crypticerya zeteki (Cockerell) are briefl y diagnosed based on the adult females. The presence of C. zeteki in Colombia is confi rmed and a key to the adult females of species of the tribe Iceryini reported in Colombia is provided. Resumen. Se reportan por primera vez a Crypticerya brasiliensis (Hempel) y Crypticerya genistae (Hempel) (Hemiptera: Monophlebidae: Iceryini) en Colombia. Las dos especies arriba mencionadas junto con Crypticerya multicicatrices Kondo y Unruh y Crypticerya zeteki (Cockerell) se diagnostican brevemente con base en morfología de las hembras adultas. Se confi rma la presencia de C. zeteki en Colombia y se provee una clave para las hembras adultas de las especies de la tribu Iceryini registradas en Colombia

Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria

Supplementary dataset from "Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria

An Oral Recombinant Vaccine in Dogs against Echinococcus granulosus, the Causative Agent of Human Hydatid Disease: A Pilot Study

Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp) and a fibrillar protein similar to paramyosin (EgA31), cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium

A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis

The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell–mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362