Inflammation in the nervous system

Perry, V.H.; Bell, M. D.; Brown, Hilary F.; Matyszak, Malgosia K.

doi:10.1016/0959-4388(95)80069-7

Cited by 190 publications

(93 citation statements)

References 49 publications

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“…TNFα is involved intimately in inflammation, immune activation, differentiation and cell death, but its complex actions are increasingly implicated in diseases of the CNS (Perry et al, 1995;Allan and Rothwell, 2001). TNFα and other cytokines are induced rapidly in response to tissue injury and infection and in the CNS (Perry et al, 1995;Allan and Rothwell, 2001). TNFα administered to primary neurons in culture causes a dosedependent cytotoxicity (Zhao et al, 2001) and neuronal apoptosis (Reimann-Philipp et al, 2001).…”

Section: The Trigger For Abnormal Ampar Trafficking In Neuronal Dysfumentioning

confidence: 99%

TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

Leonoudakis

Braithwaite²,

Beattie

et al. 2004

Neuron Glia Biol.

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Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.

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Section: The Trigger For Abnormal Ampar Trafficking In Neuronal Dysfumentioning

confidence: 99%

TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

Leonoudakis

Braithwaite²,

Beattie

et al. 2004

Neuron Glia Biol.

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“…Cell debris, cytokines and serum components gaining access to the brain through a damaged blood-brain barrier have been implicated as microglial activators (Chamak and Mallat, 1991;Lassmann et al, 1991;Benveniste, 1992;Nakajima and Kohsaka, 2001;Kadota et al, 2000;Lu et al, 2001). The microglial response comprises reactive morphological changes as well as changes in their functional properties, including proliferation, phagocytosis, migration and release of cytokines (Thomas, 1992;Perry et al, 1995;Gehrmann and Kreutzberg, 1995;Giulian, 1995). However, the response of microglia has been found to be extremely diverse and it is known that the intensity and type of activating signals from the damaged tissue condition the degree and characteristics of the microglial response.…”

Section: Introduction Mmentioning

confidence: 99%

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Vela

Yáñez

González

et al. 2002

Journal of Neurotrauma

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Ablation of the hindlimb area of the sensorimotor cortex produces degeneration in the cortex (invasive traumatic injury) and leads to retrograde and/or anterograde degeneration in the thalamus (non-invasive injury, distal reaction). This provides an useful model to study the proliferation and elimination of microglia/macrophages in different neurodegenerative conditions. Changes in the morphology, distribution and numbers of microglia in the affected cortex and thalamus were analyzed at various time points (12 h to 30 days) after injury. In parallel, proliferation was determined by immunocytochemistry for the proliferating cell nuclear antigen and cell death by the TUNEL method. Proliferation was an early event in the microglia/macrophage response (from 12 h in the cortex and from 2 days post-lesion in the thalamus) and persisted up to 30 days. The different microglia/macrophage phenotypes proliferated in a specific temporospatial pattern. In the lesioned cortex, early activation and proliferation of intrinsic microglia was accompanied, from the second post-lesion day, by monocyte entrance and proliferation of monocyte-derived cells. In contrast, accumulation of cells in the thalamus resulted from proliferation of intrinsic microglia, without apparent/significant monocytic recruitment. During the subsequent microglia/macrophages removal the majority of the cells in the cortex transformed into ameboid cells devoid of cell processes that progressively accumulated as fully-developed macrophages tissue within the lesion (3-14 days) ultimately migrating out to the meningeal connective tissue (14-30 days). Only some process-bearing cells, remaining in the cortical tissue bordering the lesion, underwent degeneration by 14-21 days post-lesion. In contrast, in the distal affected thalamic nuclei, microglial cell death occurred by 14-30 days post-lesion. Altogether, this study shows that both the origin and fate of microglia/ macrophages depend on the nature of the lesion.

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“…16 It has been shown that a single-bolus injection of IL-1 into the CNS parenchyma gives rise to delayed and localized neutrophil (PMN) recruitment, but no overt damage to CNS integrity. 17,18 However, no study has examined the consequences of chronic expression of IL-1 in the brain parenchyma, which would be more relevant to the pattern of expression observed in chronic inflammatory diseases of the CNS. In this study, we were particularly keen to determine whether the atypical recruitment profile, which is observed after a single-bolus injection of IL-1, is conserved during extended IL-1 expression and whether extended expression would result in CNS damage.…”

mentioning

confidence: 99%

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

Ferrari

Depino

Prada

et al. 2004

The American Journal of Pathology

188

149

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Interleukin-1␤ (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases. To investigate the response of the CNS to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1 into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection), there was a marked recruitment of neutrophils, vasodilatation, and breakdown of the BBB. Microglia and astrocyte activation was evident during the first 14 days post-injection. At days 8 and 14, extensive demyelination was observed but the number of neurons was not affected by any treatment. Finally, at 30 days, signs of inflammation were no longer present, there was evidence of tissue reorganization, the BBB was intact, and the process of remyelination was noticeable. In summary, our data show that chronic expression of IL-1, in contrast to its acute delivery, can reversibly damage CNS integrity and implicates this cytokine or downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases.

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Inflammation in the nervous system

Cited by 190 publications

References 49 publications

TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

Time Course of Proliferation and Elimination of Microglia/Macrophages in Different Neurodegenerative Conditions

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

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