Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures

Bronstein, David M.; Pérez‐Otaño, Isabel; Sun, Virginia; Sawin, S.B. Mullis; Chan, James; Wu, Grace C.; Hudson, Pearlie M.; Kong, Ling-Yuan; Hong, Jau–Shyong; McMillian, Michael

doi:10.1016/0006-8993(95)01189-7

Cited by 182 publications

(122 citation statements)

References 37 publications

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“…5A). In agreement with previous studies indicating that LPS-induced neurotoxicity was, at least in part, mediated via NO (Chao et al, 1992;Bronstein et al, 1995), the addition of the NO synthase inhibitor N G -nitro-L-arginine-methyl ester (1 mM) to the mesencephalic cultures inhibited the accumulation of nitrite produced after treatment for 72 hr with 1000 ng/ml LPS by 73% and reduced the loss of MAP-2-immunostained neurons by 74% (data not shown).…”

Section: Susceptibility Of Neurons In Neuron-glia Cultures From Diffesupporting

confidence: 93%

“…NO can readily react with superoxide free radicals to form the highly reactive peroxynitrite species that are capable of inflicting additional neuronal damage (Beckman et al, 1990). The importance of NO in microglia-mediated neurodegeneration is further supported by observations in which the addition of NO synthase inhibitors to neuron-glia cultures inhibits the LPS-induced accumulation of nitrite and reduces neuronal cell loss (Boje and Arora, 1992;Chao et al, 1992;Bronstein et al, 1995). In addition to NO, TNF␣ has been suspected to be an important mediator of LPSinduced inflammation, as evidenced by the findings that levels of TNF␣ in the CSF of patients with bacterial meningitis correlate with concentrations of bacterial endotoxin in the brain (Arditi et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

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Regional Difference in Susceptibility to Lipopolysaccharide-Induced Neurotoxicity in the Rat Brain: Role of Microglia

et al. 2000

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Inflammation in the brain has been increasingly associated with the development of a number of neurological diseases. The hallmark of neuroinflammation is the activation of microglia, the resident brain immune cells. Injection of bacterial endotoxin lipopolysaccharide (LPS) into the hippocampus, cortex, or substantia nigra of adult rats produced neurodegeneration only in the substantia nigra. Although LPS appeared to impact upon mesencephalic neurons in general, an extensive loss of dopaminergic neurons was observed. Analysis of the abundance of microglia revealed that the substantia nigra had the highest density of microglia. When mixed neuron-glia cultures derived from the rat hippocampus, cortex, or mesencephalon were treated with LPS, mesencephalic cultures became sensitive to LPS at a concentration as low as 10 ng/ml and responded in a dose-dependent manner with the production of inflammatory factors and a loss of dopaminergic and other neurons. In contrast, hippocampal or cortical cultures remained insensitive to LPS treatment at concentrations as high as 10 g/ml. Consistent with in vivo observations, mesencephalic cultures had fourfold to eightfold more microglia than cultures from other regions. The positive correlation between abundance of microglia and sensitivity to LPS-induced neurotoxicity was further supported by the observation that supplementation with enriched microglia derived from mesencephalon or cortex rendered LPS-insensitive cortical neuron-glia cultures sensitive to LPS-induced neurotoxicity. These data indicate that the region-specific differential susceptibility of neurons to LPS is attributable to differences in the number of microglia present within the system and may reflect levels of inflammation-related factors produced by these cells.

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Section: Susceptibility Of Neurons In Neuron-glia Cultures From Diffesupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Regional Difference in Susceptibility to Lipopolysaccharide-Induced Neurotoxicity in the Rat Brain: Role of Microglia

et al. 2000

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“…LPS is a widely used and powerful tool for the activation of microglia and of peripheral immune cells. Although LPS has no known direct toxic effect on neurons, it activates microglia to release a host of neurotoxic factors to induce neuronal death (Bronstein et al, 1995;Araki et al, 2001;Liu et al, 2002c). In contrast to the action of LPS, certain agents are known to have a direct neurotoxic effect.…”

Section: Multiple Pathways Leading To Microglial Activationmentioning

confidence: 99%

Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism

Block

Hong

2005

Progress in Neurobiology

1,343

994

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“…Further studies showed that chronic activation of microglia by MPTP leads to their clustering around DA neurons and transformation in phagocytic cells ( [11,23]). …”

Section: Animal Models Of Parkinson's Diseasementioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

262

204

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a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

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Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures

Cited by 182 publications

References 37 publications

Regional Difference in Susceptibility to Lipopolysaccharide-Induced Neurotoxicity in the Rat Brain: Role of Microglia

Regional Difference in Susceptibility to Lipopolysaccharide-Induced Neurotoxicity in the Rat Brain: Role of Microglia

Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

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