Encapsulated galanin-producing cells attenuate focal epileptic seizures in the hippocampus.

Purpose: Encapsulated cell biodelivery (ECB) is a relatively safe approach, since the devices can be removed in the event of adverse effects. The main objectives of the present study were to evaluate whether ECB could be a viable alternative of cell therapy for epilepsy. We therefore developed a human cell line producing galanin, a neuropeptide that has been shown to exert inhibitory effects on seizures, most likely acting via decreasing glutamate release from excitatory synapses.

Congestive heart failure in rats is associated with increased collecting duct vasopressin sensitivity and vasopressin type 2 receptor reexternalization.

A number of studies have shown that rats with congestive heart failure (CHF) have increased protein levels of the vasopressin (AVP)-regulated water channel aquaporin-2 (AQP2) even during conditions with unchanged circulating levels of AVP, suggesting an increase in the sensitivity of the AVP type 2 (V2) receptor in experimental CHF. The present study was aimed at investigating AVP signaling in rats with moderate CHF (left ventricular end diastolic pressure >10 mmHg; normal plasma AVP levels) induced by ligation of the left anterior descending coronary artery. Sham-operated rats were used as controls.

Encapsulated cell-based biodelivery of meteorin is neuroprotective in the quinolinic acid rat model of neurodegenerative disease.

Purpose: Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects against quinolinic acid (QA)-induced excitotoxicity.

Methods: Meteorin-producing ARPE-19 cells were loaded into EC biodelivery devices and implanted into the striatum of rats.

Meteorin is a chemokinetic factor in neuroblast migration and promotes stroke-induced striatal neurogenesis.

Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro.

Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo.

Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.

Lentiviral delivery of meteorin protects striatal neurons against excitotoxicity and reverses motor deficits in the quinolinic acid rat model.

Meteorin is a newly discovered secreted protein involved in both glial and neuronal cell differentiation, as well as in cerebral angiogenesis during development; but effects in the adult nervous system are unknown. The growth factor-like properties and expression of Meteorin during the development of the nervous system raises the possibility that it might possess important neuroprotective or regenerative capabilities. This report is the first demonstration that Meteorin has potent neuroprotective effects in vivo.

Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain.

Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device, capable of local delivery of NGF.

Characterization of Meteorin--an evolutionary conserved neurotrophic factor.

Growth factors control cellular growth, proliferation, and differentiation and may have therapeutic applications. In this study, we focus on Meteorin which is a member of a largely uncharacterized evolutionary conserved two-member growth factor family. Our analysis shows that Meteorin is expressed in the central nervous system both during development and in adult mice.

The Drosophila gene CG9918 codes for a pyrokinin-1 receptor.

The database from the Drosophila Genome Project contains a gene, CG9918, annotated to code for a G protein-coupled receptor. We cloned the cDNA of this gene and functionally expressed it in Chinese hamster ovary cells. We tested a library of about 25 Drosophila and other insect neuropeptides, and seven insect biogenic amines on the expressed receptor and found that it was activated by low concentrations of the Drosophila neuropeptide, pyrokinin-1 (TGPSASSGLWFGPRLamide; EC50, 5 x 10(-8) M).

Uncoupling of vasopressin signaling in collecting ducts from rats with CBL-induced liver cirrhosis.

Vasopressin (AVP) stimulates collecting duct water reabsorption through cAMP-mediated membrane targeting and increased expression of the aquaporin-2 (AQP2) water channel. Rats with liver cirrhosis induced by common bile duct ligation (CBL) show decreased protein expression of AQP2 despite increased plasma concentrations of AVP. The present study was conducted to investigate possible mechanisms behind this uncoupling of AVP signaling.

Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis.

This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy of the inner stripe of the outer medulla (ISOM) and increased natriuretic effect of furosemide in vivo, and semiquantitative immunoblotting showed increased expression of the furosemide-sensitive Na-K-2Cl cotransporter type 2 (NKCC2) in ISOM from CBL rats. DNX significantly attenuated the sodium retention in the CBL rats, which was associated with normalization of the natriuretic effect of furosemide, as well as a significant reduction in the expression of NKCC2 in the ISOM.