James J. Vornov

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We describe here a new strategy for the treatment of stroke, through the inhibition of NAALADase (N-acetylated-alpha-linked-acidic dipeptidase), an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. We demonstrate that the newly described NAALADase inhibitor 2-PMPA(More)
Excessive activation of excitatory amino acid receptors has been implicated in the neuronal degeneration caused by ischemia, hypoglycemia, and prolonged seizures. We have observed directly the time course and regional vulnerability of hippocampal neurons to glutamate receptor-mediated injury in organotypic hippocampal cultures, a preparation which combines(More)
Profound hypoglycemia selectively damages CA1 and the dentate gyrus of the hippocampus. We have examined the time course of hippocampal neuronal injury in organotypic cultures following in vitro "hypoglycemia," using the fluorescent vital dye propidium iodide to observe directly the regional distribution of early neuronal membrane injury in living cultures.(More)
The Bax protein is widely known as a pro-apoptotic Bcl-2 family member that when overexpressed can trigger apoptosis in multiple cell types and is important for the developmental cell death of neurons. However, Bax was found here to be a potent inhibitor of neuronal cell death in mice infected with Sindbis virus. Newborn mice, which are highly susceptible(More)
BACKGROUND AND PURPOSE The hippocampus demonstrates a regional pattern of vulnerability to ischemic injury that depends on its characteristic differentiation and intrinsic connections. We now describe a model of ischemic injury using organotypic hippocampal culture, which preserves the anatomic differentiation of the hippocampus in long-term tissue culture.(More)
Acidosis is a universal response of tissue to ischemia. In the brain, severe acidosis has been linked to worsening of cerebral infarction. However, milder acidosis can have protective effects. As part of our investigations of the therapeutic window in our neuronal tissue culture model of ischemia, we investigated the effects of acidosis during recovery from(More)
Organotypic cultures of the brain provide a unique opportunity to directly examine the regional vulnerability of specific brain regions like the hippocampus. Two well-characterized models of oxidative stress were used to examine the regional vulnerability of the hippocampus. Endogenous oxidative stress was induced by blocking synthesis of the endogenous(More)
BACKGROUND AND OBJECTIVE We studied the pharmacokinetics and pharmacodynamics of GPI 15715 (Aquavan injection), a new water-soluble prodrug metabolized to propofol by hydrolysis. METHODS Nine adult male Sprague-Dawley rats (398 +/- 31 g) received a bolus dose of 40 mg GPI 15715. The plasma concentrations of GPI 15715 and propofol were determined from(More)
Glutamate (Glu) and aspartate (Asp) are considered to be the neurotransmitters of the optic pathway in submammalian species, but their roles in mammals is uncertain. Recently, N-acetylaspartylglutamate (NAAG) has been proposed as a neurotransmitter in mammalian optic pathway; however, the release of endogenous NAAG on stimulation of the optic pathway has(More)
The noradrenergic innervation of the trigeminal motor nucleus of the rat can be increased severalfold by neonatal treatment with the neurotoxin, 6-hydroxydopamine. The brainstem projections to the nucleus were studied by injecting HRP into the nucleus of normal and noradrenergically hyperinnervated rats. In order to identify the source of the noradrenergic(More)