The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1β-induced neurodegeneration

Radesäter, Ann-Cathrin; Johansson, Sofie; Öberg, Caroline; Luthman, Johan

doi:10.1007/bf03033173

Cited by 22 publications

(17 citation statements)

References 51 publications

(64 reference statements)

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“…IL-1ß per se is neurotoxic and its effects are apparently mediated through NMDA excitotoxins such as quinolinic acid (Fornstedt-Wallin et al, 1999), possibly derived from astrocytes (Guillemin et al, 2000) or microglia (Alberati-Giani et al, 1996). In order to study putative neuroprotective effects of the NMDA receptor antagonist dizocilpine (MK-801) and the vitamin E analog trolox on hippocampal pyramidal neurons (which possess IL-1 receptors), Radesäter et al (2003) …”

Section: Effect Of Trolox and Nmda On Il-1ß-induced Neurodegenerationmentioning

confidence: 99%

Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review

Kostrzewa

Segura‐Aguilar

2003

neurotox res

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Cellular mechanisms involved in neurodegeneration and neuroprotection are continuing to be explored, and this paper focuses on some novel discoveries that give further insight into these processes. Oligodendrocytes and activated astroglia are likely generators of the pro-inflammatory cytokines, such as the tumor necrosis factor family and interleukin family, and these glial support cells express adhesion receptors (e.g., VCAM) and release intercellular adhesion molecules (ICAM) that have a major role in neuronal apoptosis. Even brief exposure to some substances, in ontogeny and sometimes in adulthood, can have lasting effects on behaviors because of their prominent toxicity (e.g., NMDA receptor antagonists) or because they sensitize receptors (e.g., dopamine D2 agonists), possibly permanently, and thereby alter behavior for the lifespan. Cell cycle genes which may be derived from microglia, are the most-recent entry into the neuroprotection schema. Neuroprotection afforded by some common substances (e.g., melatonin) and uncommon substances [e.g., nicotine, green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), trolox], ordinarily thought to be simple radical scavengers, now are thought to invoke previously unsuspected cellular mechanisms in the process of neuroprotection. Although Alzheimer's disease (AD) has features of a continuous spectrum of neural and functional decline, in vivo PET imaging and and functional magnetic resonance imaging, indicate that AD can be staged into an early phase treatable by inhibitors of beta and gamma secretase; and a late phase which may be more amenable to treatment by drugs that prevent or reverse tau phosphorylation. Neural transplantation, thought to be the last hope for neurally injured patients (e.g., Parkinsonians), may be displaced by non-neural tissue transplants (e.g., human umbilical cord blood; Sertoli cells) which seem to provide similar neurotrophic support and improved behavior - without posing the major ethical dilemma of removing tissue from aborted fetuses. The objective of this paper is to invite added research into the newly discovered (or postulated) novel mechanisms; and to stimulate discovery of additional mechanisms attending neurodegeneration and neuroprotection.

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Section: Effect Of Trolox and Nmda On Il-1ß-induced Neurodegenerationmentioning

confidence: 99%

Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review

Kostrzewa

Segura‐Aguilar

2003

neurotox res

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“…LPS has also been shown to induce the expression of IL-1β in mixed glial cell cultures (Chauvet et al, 2001). This finding is of particular relevance in the present context, since we have previously shown that IL-1β is neurotoxic to NMDA-R1 immunoreactive cells in hippocampal roller-drum cultures (Luthman et al, 1998;Radesäter et al, 2003). Activation of microglia and macrophages, causing a production of different neurotoxic factors, may therefore be critically involved in LPS-mediated neurodegeneration in hippocampal slice cultures.…”

Section: Discussionmentioning

confidence: 80%

“…With LPS as a tool to induce general inflammatory reactions, possibilities are presented to study the link between inflammation and neurodegeneration. For example, we have been able to induce both IL-1β (Luthman et al, 1998;Radesäter et al, 2003) and Aβ peptide- (Johansson et al, 2005) mediated neurodegeneration in the culture system used in the present study. Neuroinflammation, APP processing and Aβ neurotoxicity may in fact be related.…”

Section: Discussionmentioning

confidence: 88%

“…For example, the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNFα) as well as other inflammatory mediators, such as NO, are produced in the brain by activated microglia (Bal-Price and Brown, 2001). Since several of the factors identified in neuroinflammatory processes may be toxic to nerve cells (Dawson et al, 1994;Rothwell and Hopkins, 1995;Jeohn et al, 1998;Bal-Price and Brown, 2001;Radesäter et al, 2003), it is believed that inflammation may contribute to neurodegeneration (McGeer and McGeer, 1995;Allan and Rothwell, 2003).…”

Section: Introductionmentioning

confidence: 95%

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Salmonella lipopolysaccharide (LPS) mediated neurodegeneration in hippocampal slice cultures

Johansson

Bohman²,

Radesäter

et al. 2005

neurotox res

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Neuroinflammation has been suggested to play an integral role in the pathophysiology of various neurodegenerative diseases. Bacterial lipopolysaccharide (LPS) endotoxins are general activators of immune-cells, including microglial cells, which induce expression of pro-inflammatory factors. The aim of this study was to characterize neurodegenerative effects of exposure to LPS, derived from Salmonella abortus equi bacteria, in an in vitro brain slice culture system. Quasi-monolayer cultures were obtained using roller-drum incubations of hippocampal slices from neonatal Sprague Dawley rats for three weeks. Microglia/macrophages were identified in the monolayer cultures by CD11b immunostaining, while neuronal populations identified included N-methyl-D-aspartate (NMDA-R1) receptor immunoreactive pyramidal neurons and smaller GABA-immunoreactive cells. Following exposure to LPS (100 ng/ml) an increased density of CD11b positive cells was found in the cultures. In addition, the LPS exposure produced a concentration-dependent loss of the NMDA-R1 immunoreactive neurons in the cultures which was substantial at 100 ng/ml LPS. The loss of NMDA-R1 cells was apparent already after 24 h exposure to LPS and seemed to be primarily due to necrotic-like cell death. However, a continued loss of cells was found when cultures were analyzed at 72 h, concomitant with an increase in the expression of p53 in the NMDA-R1 cells and TUNEL labeling of a few cells. Also the number of GABA-immunoreactive cells decreased rapidly and to a substantial extent after 24 h exposure to LPS, with a continued decrease up to 72 h. The findings show that Salmonella LPS increases the density of CD11b positive cells and acts as a potent neurotoxin in hippocampal roller-drum slice cultures. The LPS-induced neurodegeneration has both necrotic- and apoptotic-like properties and appears to be non-selective, affecting both pyramidal and GABA neurons. LPS-induced neurotoxicity in slice cultures may be a useful system to study processes involved in inflammatory-mediated neurodegeneration.

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“…27,28) Neuroprotective effect of trolox is further supported by its protective effect in amyloid b-mediated neurotoxicity, 29) and interleukin (IL-1b) induced neurodegeneration. 30) In addition to protective effects in neurotoxicity models, trolox counteracted the toxic effects of S-morpholinosydnonimine (SIN-1), a peroxynitrite donor in lung epithelial cells, 31) and in arrhythmias in isolated heart preparations. 32) Consistent with the earlier reports, we have also observed significant increase in the level of MDA in ischemic animals indicating oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Trolox in Global Cerebral Ischemia in Gerbils

Gupta

Sharma

2006

Biological & Pharmaceutical Bulletin

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Stroke is the third leading cause of death and a major cause of long-term disability in industrialized countries. Dramatic reduction of oxygen in stroke may lead to ischemia of the whole brain (global ischemia) or of defined cerebral territories (focal ischemia) depending on the cerebral artery occluded.1) Global cerebral ischemia is commonly an outcome of a range of clinical conditions, which comprises cardiac arrest, closed head injury, coronary artery bypass surgery etc. The most affected brain area as a consequence of global ischemia is CA1 neurons of the hippocampus. Neuronal death in global ischemia precedes 1-3 d after insult, a process referred as delayed neuronal death. 2-4)The pathophysiological mechanisms leading to neuronal injury in ischemic stroke are complex and multifactorial. Ischemia induced brain damages are accompanied by biochemical alterations and neurological sequelae.1) There are substantial experimental evidences that reactive oxygen species (ROS) are produced in the brain during ischemia and reperfusion injury.5) ROS such as superoxide radical, hydroxyl radical and hydrogen peroxide contributes to ischemic brain damage.5) Superoxide can react with nitric oxide to form peroxynitrite, a potent oxidant. It has been proposed that many of the toxic effects of nitric oxide are due to the generation of peroxynitrite. Peroxynitrite can directly react with target biomolecules like DNA, protein, via one or two electron oxidations. 5-7)Antioxidants such as (Ϫ)-epigallocatechin gallate, melatonin, curcumin, FeTMPyP and FeTPPS have been demonstrated to ameliorate neuronal damage in cerebral ischemic reperfusion injury. 3,[8][9][10][11] Antioxidant activity of trolox (6-hydroxy-2,5,7,8-tetramethyl chroman-2-carboxylic acid) a cellpermeable, water-soluble derivative of vitamin E has been established in vitro and in vivo conditions. 12-15) However its neuroprotective effects have not been investigated in global cerebral ischemia. Therefore, in the present study, the neuroprotective potential of trolox was investigated in bilateral carotid artery occlusion induced global cerebral ischemia in Mongolian gerbils. MATERIALS AND METHODS AnimalsAdult male Mongolian gerbils (Meriones unguiculatus) weighing 60-80 g were obtained from Central Animal Facility (CAF), NIPER for this study. They were provided with standard diet and water ad libitum and were maintained at 22Ϯ2°C and a 12 : 12 h light : dark cycle. All the procedures used in this study were approved by Institutional Animal Ethics Committee (IAEC), NIPER.Materials Trolox was purchased from Calbiochem Inc., U.S.A. Cresyl violet and malondialdehyde were purchased from Sigma Chemical Company, U.S.A. Rest of the chemicals were of analytical grade and were purchased from commercial suppliers.Treatment Schedule Gerbils were divided into sham, vehicle-treated ischemic and trolox-treated (3, 10, 30 mg/kg i.p.) ischemic groups. Phosphate buffer saline (pH 7.4) was used as a vehicle for trolox. Trolox was administered 30 min before occlusion.Induction of Transie...

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The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1β-induced neurodegeneration

Cited by 22 publications

References 51 publications

Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review

Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review

Salmonella lipopolysaccharide (LPS) mediated neurodegeneration in hippocampal slice cultures

Neuroprotective Effects of Trolox in Global Cerebral Ischemia in Gerbils

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