TNFR1 mediates increased neuronal membrane EAAT3 expression after in vivo cerebral ischemic preconditioning.

A short ischemic event (ischemic preconditioning) can result in subsequent resistance to severe ischemic injury (ischemic tolerance). Glutamate is released after ischemia and produces cell death. It has been described that after ischemic preconditioning, the release of glutamate is reduced.

Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport.

Background And Purpose: Cytidine-5'-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine, has shown beneficial effects in a number of CNS injury models including cerebral ischemia. Citicoline is the only neuroprotectant that has proved efficacy in patients with moderate to severe stroke. However, the precise mechanism by which citicoline is neuroprotective is not fully known.

Beta-amyloid25-35 inhibits glutamate uptake in cultured neurons and astrocytes: modulation of uptake as a survival mechanism.

Glutamate transporters are vulnerable to oxidants resulting in reduced uptake function. We have studied the effects of beta-amyloid(25-35) (beta A(25-35)) on [(3)H]-glutamate uptake on cortical neuron or astrocyte cultures in comparison with a scrambled peptide (SCR) and dihydrokainic acid (DHK), a prototypic uptake inhibitor. beta A(25-35) was more potent than DHK in inhibiting glutamate uptake and the effects of both were more marked on astrocytes than on neurons.

In vitro ischemic tolerance involves upregulation of glutamate transport partly mediated by the TACE/ADAM17-tumor necrosis factor-alpha pathway.

A short ischemic event [ischemic preconditioning (IPC)] can result in a subsequent resistance to severe ischemic injury (ischemic tolerance). Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage found after cerebral ischemia, its expression and neuroprotective role in models of IPC have also been described. Regarding the role of TNF-alpha convertase (TACE/ADAM17), we have recently shown its upregulation in rat brain after IPC induced by transient middle cerebral artery occlusion and that subsequent TNF-alpha release accounts for at least part of the neuroprotection found in this model.

Expression and function of tumour necrosis factor-alpha-converting enzyme in the central nervous system.

Tumour necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE/ADAM17) is a membrane protein belonging to the ADAM (a disintegrin and a metalloprotease) family able to cleave various membrane proteins, including the transmembrane form of TNF-alpha at its physiological processing site. Being an ADAM, TACE may mediate not only proteolysis but also adhesive interactions; however, the role of the disintegrin domain of TACE has not been studied. In the central nervous system (CNS), little is known about the physiological role of TACE, but some important pathophysiological functions have been reported recently, with both neurotoxic and neuroprotective repercussions.

TACE/ADAM17-TNF-alpha pathway in rat cortical cultures after exposure to oxygen-glucose deprivation or glutamate.

The role of the tumor necrosis factor (TNF)-alpha convertase (TACE/ADAM17) in the adult nervous system remains poorly understood. The authors have previously demonstrated that TACE is upregulated in rat forebrain slices exposed to oxygen-glucose deprivation (OGD). They have now used rat mixed cortical cultures exposed to OGD or glutamate to study (1) TACE expression and localization, and (2) the effects of TNF-alpha release on cell viability.

Inhibition of glutamate release via recovery of ATP levels accounts for a neuroprotective effect of aspirin in rat cortical neurons exposed to oxygen-glucose deprivation.

Background And Purpose: Aspirin is preventive against stroke not only because of its antithrombotic properties but also by other direct effects. The aim of this study was to elucidate its direct neuroprotective effects.

Methods: Viability parameters, glutamate release and uptake, and ATP levels were measured in cultured cortical neurons exposed to oxygen-glucose deprivation (OGD).

Modulation of adrenergic receptors during left ventricular hypertrophy development and after regression by captopril.

The objective of this study was to analyze adrenergic receptors during cardiac hypertrophy development, after establishment of cardiac hypertrophy and after regression of cardiac hypertrophy by an angiotensin-converting enzyme inhibitor. Left ventricular hypertrophy (LVH) was induced by abdominal aortic stenosis. After surgery, plasma norepinephrine concentrations (PNE) and left ventricular adrenergic receptors from rat hearts subjected to aortic stenosis were assessed during cardiac hypertrophy development (at 3, 7, 15, and 30 days of aortic stenosis), once cardiac hypertrophy had been established (7 and 14 weeks after the stenosis) and after regression of cardiac hypertrophy by an antihypertensive dose (200 mg/kg/day) of captopril.

Neuroprotective effects of DETA-NONOate, a nitric oxide donor, on hydrogen peroxide-induced neurotoxicity in cortical neurones.

Nitric oxide (NO) has been proposed to exert neuroprotective actions against oxidative damage acting directly as an antioxidant; in addition, it has also been suggested that NO might be cytoprotective by increasing cyclic GMP concentrations via activation of soluble guanylate cyclase. In this context, we have previously shown that cyclic GMP elevations confer cytoprotection against the neurotoxicity induced by SIN-1 in the presence of superoxide dismutase, conditions in which cell death seems to be a consequence of hydrogen peroxide (H2O2) formation. We have now found that H2O2 (20-100 microM) causes neurotoxicity in 1-week-old rat cortical neurones and that this effect is inhibited by the NO donor DETA-NONOate (1-10 microM).

Neuronal death induced by SIN-1 in the presence of superoxide dismutase: protection by cyclic GMP.

The nitrovasodilator 3-morpholinosydnonimine (SIN-1) slowly decomposes to release both nitric oxide (NO) and superoxide (O2-) and thereby produces peroxynitrite (ONOO-), a powerful oxidant which has been proposed to mediate the toxic actions caused by NO. Indeed, ONOO has been shown to cause neuronal death and it has been proposed to occur in different disorders of the CNS such as brain ischaemia, AIDS-associated dementia, amyothrophic lateral sclerosis, etc. We have found that SIN-1 was only slightly toxic to 1-week-old rat cortical neurones in primary culture (LC50=2.

Lesions of the ventral noradrenergic bundle prevent the rise in blood pressure induced by social deprivation stress in the rat.

1. Hypertension can be induced by some types of stress in the rat. The aim of the present work was to study the putative implication of brain norepinephrine (NE) in blood pressure increase due to social deprivation stress.

Ontogenesis of muscarinic receptors in cultured rat hippocampal cells.

The ontogeny of muscarinic cholinergic receptors was studied in primary cultures of dissociated rat hippocampal cells. The specific [3H]quinuclidinyl benzilate [( 3H]QNB) to intact cells was detected after two days in culture. Scatchard analysis revealed only a unique binding site at all of the days tested, with a very high affinity (0.