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Previous studies demonstrated that the rat neuron-specific enolase (NSE) promoter is effective for transgene expression in the brain in a variety of adeno-associated virus-2 vectors. This study evaluated the dose response and longer time course of this promoter and compared it to two cytomegalovirus/chicken beta-actin hybrid (CBA) promoter-based systems.(More)
While activation of alpha7 nicotinic receptors protects neurons from a variety of apoptotic insults in vitro, little is known about this neuroprotective action in vivo, especially under amyloidogenic conditions that mimic Alzheimer's disease. We therefore investigated the effects of 4OH-GTS-21, a selective partial agonist for these receptors, on(More)
alpha7 Nicotinic receptors are calcium permeant and provide neuroprotection against many insults. We investigated the roles of intracellular calcium ions and downstream calcium channels in this protection. The alpha7 agonist GTS-21 prevented pheochromocytoma cell death induced by nerve growth factor + serum deprivation over a 3-day interval. This effect was(More)
OBJECT Achieving distribution of gene-carrying vectors is a major barrier to the clinical application of gene therapy. Because of the blood-brain barrier, the distribution of genetic vectors to the central nervous system (CNS) is even more challenging than delivery to other tissues. Direct intraparenchymal microinfusion, a minimally invasive technique, uses(More)
Nerve growth factor (NGF) therapy has been proposed to treat cognitive impairments in aged patients including those with Alzheimer's disease. Various viral vectors, including adeno-associated virus serotype 2 (AAV2), have been investigated for their ability to deliver NGF in brain. In this study, hybrid vectors (AAV2/5) consisting of the genome of(More)
Although NGF gene therapy has been proposed to treat age- or disease-related brain cholinergic decline, little is known about the ectopic expression or function of this trophic factor after transduction in the brain especially over long intervals. The neuron-targeting, recombinant adeno-associated virus serotype 2 (rAAV2) vector was used to express mouse(More)
BACKGROUND To date, recombinant tissue plasminogen activator (rtPA) is the only approved drug for ischemic stroke. It is intravenously administered functioning as a thrombolytic agent and is used to obtain reperfusion of the affected area of the brain. Excitotoxicity, inflammation and apoptosis are all involved in delayed neuronal death following stroke and(More)
Polyethylenimine (PEI) is an effective vehicle for in vivo gene delivery in many tissues including brain. PEI mediates transgene expression in brain neurons and glia. To investigate whether PEI-mediated nerve growth factor (NGF) gene transfer protected axotomized septal cholinergic neurons, we injected linear PEI (in vivo jetPEI, Qbiogene) complexed with a(More)
Isotopically labeled nitrate (15 NO) was added continuously to the Rowley estuary, Massachusetts, for 22 d to Ϫ 3 assess the transport, uptake, and cycling of terrestrially derived nitrogen during a period of high river discharge and low phytoplankton activity. Isotopic enrichment of the 3.5-km tidal prism (150,000 m 3) was achieved for the 3 weeks and(More)
The gene encoding for the Swedish double mutation (K595N/M596L) of amyloid precursor protein (APP695Swe) was expressed bilaterally in adult rat hippocampus to determine its long-term effects on memory-related behavior as well as amyloid deposition. Recombinant adeno-associated viral serotype 2 (rAAV2) vectors were injected that contained either(More)