Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid.

CNS repair requires both effector and regulatory T cells with distinct temporal and spatial profiles.

Monocyte-derived macrophages (mo-MΦs) and T cells have been shown to contribute to spinal cord repair. Recently, the remote brain choroid plexus epithelium (CP) was identified as a portal for monocyte recruitment, and its activation for leukocyte trafficking was found to be IFN-γ-dependent. Here, we addressed how the need for effector T cells can be reconciled with the role of inflammation-resolving immune cells in the repair process.

IFN-γ-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair.

Infiltrating T cells and monocyte-derived macrophages support central nervous system repair. Although infiltration of leucocytes to the injured central nervous system has recently been shown to be orchestrated by the brain's choroid plexus, the immunological mechanism that maintains this barrier and regulates its activity as a selective gate is poorly understood. Here, we hypothesized that CD4(+) effector memory T cells, recently shown to reside at the choroid plexus stroma, regulate leucocyte trafficking through this portal through their interactions with the choroid plexus epithelium.

CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging.

The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circulation, the epithelial layers of the choroid plexus (CP) are constitutively populated with CD4(+) effector memory cells with a T-cell receptor repertoire specific to CNS antigens.

Angiotensin 1-7 as means to prevent the metabolic syndrome: lessons from the fructose-fed rat model.

We studied the effects of chronic angiotensin 1-7 (Ang 1-7) treatment in an experimental model of the metabolic syndrome, i.e., rats given high-fructose/low-magnesium diet (HFrD).

Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using near infrared light.

Purpose: We evaluated the efficacy and safety of photochemical corneal stiffening by palladium bacteriochlorin 13'-(2-sulfoethyl)amide dipotassium salt (WST11) and near infrared (NIR) illumination, using ex vivo and in vivo rabbit eye models.

Methods: Corneas of post mortem rabbits and living rabbits were pretreated topically with 2.5 mg/mL WST11 in saline or in 20% dextran T-500 (WST-D), washed and illuminated with an NIR diode laser (755 nm, 10 mW/cm(2).

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas.

L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase(hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma.

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas.

L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate-oxaloacetate transaminase (hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma.

Immunomodulation by poly-YE reduces organophosphate-induced brain damage.

Accidental organophosphate poisoning resulting from environmental or occupational exposure, as well as the deliberate use of nerve agents on the battlefield or by terrorists, remain major threats for multi-casualty events, with no effective therapies yet available. Even transient exposure to organophosphorous compounds may lead to brain damage associated with microglial activation and to long-lasting neurological and psychological deficits. Regulation of the microglial response by adaptive immunity was previously shown to reduce the consequences of acute insult to the central nervous system (CNS).

Abnormal changes in NKT cells, the IGF-1 axis, and liver pathology in an animal model of ALS.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation. Circulating CD4(+) T cells are required for controlling the local detrimental inflammation in neurodegenerative diseases, and for supporting neuronal survival, including that of MN. T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it.

Survival and size are differentially regulated by placental and fetal PKBalpha/AKT1 in mice.

The importance of placental circulation is exemplified by the correlation of placental size and blood flow with fetal weight and survival during normal and compromised human pregnancies in such conditions as preeclampsia and intrauterine growth restriction (IUGR). Using noninvasive magnetic resonance imaging, we evaluated the role of PKBalpha/AKT1, a major mediator of angiogenesis, on placental vascular function. PKBalpha/AKT1 deficiency reduced maternal blood volume fraction without affecting the integrity of the fetomaternal blood barrier.

A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy.

We have generated a mouse that cannot synthesize very long acyl chain (C22-C24) ceramides (Pewzner-Jung, Y., Park, H., Laviad, E.

Uterine DCs are crucial for decidua formation during embryo implantation in mice.

Implantation is a key stage during pregnancy, as the fate of the embryo is often decided upon its first contact with the maternal endometrium. Around this time, DCs accumulate in the uterus; however, their role in pregnancy and, more specifically, implantation, remains unknown. We investigated the function of uterine DCs (uDCs) during implantation using a transgenic mouse model that allows conditional ablation of uDCs in a spatially and temporally regulated manner.