Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function

Raivich, Gennadij; Bohatschek, Marion; Kloss, Christian U.A.; Werner, Alexander; Jones, Leonard L.; Kreutzberg, Georg W.

doi:10.1016/s0165-0173(99)00007-7

Cited by 764 publications

(650 citation statements)

References 281 publications

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“…31 It belongs to the neuropoietin family of cytokines, 32 and has both direct and indirect neurotrophic effects on neurons. 33 In TBI patients, IL-6 has been reported to be highly elevated in CSF and to a lesser extent in serum; serum concentrations were associated with increased acute phase proteins (C-reactive protein, fibrinogen, and ␣1-antitrypsin) and with severe BBB dysfunction.…”

Section: Interleukin-6mentioning

confidence: 99%

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

2010

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Summary:Despite dramatic improvements in the management of traumatic brain injury (TBI), to date there is no effective treatment available to patients, and morbidity and mortality remain high. The damage to the brain occurs in two phases, the initial primary phase being the injury itself, which is irreversible and amenable only to preventive measures to minimize the extent of damage, followed by an ongoing secondary phase, which begins at the time of injury and continues in the ensuing days to weeks. This delayed phase leads to a variety of physiological, cellular, and molecular responses aimed at restoring the homeostasis of the damaged tissue, which, if not controlled, will lead to secondary insults. The development of secondary brain injury represents a window of opportunity in which pharmaceutical compounds with neuroprotective properties could be administered. To establish effective treatments for TBI victims, it is imperative that the complex molecular cascades contributing to secondary injury be fully elucidated. One pathway known to be activated in response to TBI is cellular and humoral inflammation. Neuroinflammation within the injured brain has long been considered to intensify the damage sustained following TBI. However, the accumulated findings from years of clinical and experimental research support the notion that the action of inflammation may differ in the acute and delayed phase after TBI, and that maintaining limited inflammation is essential for repair. This review addresses the role of several cytokines and chemokines following focal and diffuse TBI, as well as the controversies around the use of therapeutic anti-inflammatory treatments versus genetic deletion of cytokine expression.

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Section: Interleukin-6mentioning

confidence: 99%

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

2010

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“…Neuronal cell death and demyelination occur in some of these LSDs [21][22][23] and are often accompanied by astrogliosis and microgliosis that appear mostly in areas of severe neuronal vacuolation. [24][25][26] The presence of reactive astrocytes is indicative of an elicited neuroinflammatory response, and the biochemical heterogeneity and adaptive plasticity may reflect differences in microenvironmental cues, such as the combination of cytokines, growth factors, adhesion molecules, and other signals emanating from injured neurons, activated microglia, endothelial cells, and vascular components. [27][28][29] As mentioned in the Introduction, the amount and composition of gangliosides in a cell is species-and cell type-specific.…”

Section: Metabolism Of Gangliosidesmentioning

confidence: 99%

Gangliosides as apoptotic signals in ER stress response

d’Azzo

Tessitore²,

Sano

2006

Cell Death Differ

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Renewed attention has been given lately to gangliosides and to their function as intracellular messengers of the adaptive responses to stress. Gangliosides are vital components of cell membranes; therefore, deleterious consequences can result from changes in their chemical composition and concentration, that is, membrane dynamics and structure can be altered as can the behavior of other membrane proteins. The importance of gangliosides in human health is evident in neurodegenerative diseases associated with defects in their degradation. As key modulators of intracellular calcium flux, gangliosides are involved in cellular processes downstream of calcium signaling. In this review, we focus on the effect of ganglioside accumulation on the endoplasmic reticulum calcium homeostasis and on the integrity of the mitochondrial membranes. We discuss how these events elicit an apoptotic program that ultimately leads to cell death. Owing to interorganelle crosstalk, these events are not necessarily self-contained, and gangliosides may serve as the common factor.

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“…18,38 Recent studies have indicated that some molecules released by microglia may be harmful in acute brain insults and neurodegenerative diseases. 39 Therefore, we also looked for the ability of the three cell types to release glutamate, in particular microglia. In fact, glutamate is known as a cytotoxic molecule released from activated microglia.…”

Section: Introductionmentioning

confidence: 99%

Biological risks for neurological abnormalities associated with hyperbilirubinemia

et al. 2009

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Unconjugated bilirubin (UCB) injury to glial cells leads to the secretion of glutamate and elicits a typical inflammatory response. Release of pro-inflammatory cytokines may influence gliogenesis and neurogenesis, and lead to deficits in learning and memory. Glutamate metabolism dysregulation and overexpression of tumor necrosis factor-a (TNF-a) and interleukin (IL)-1b are consistent with schizophrenia neuropathology. Recently, an increased prevalence of schizophrenia was reported in individuals with Gilbert's syndrome and among those who have had elevated levels of UCB in the neonatal life. In this review, we explore the reactivity of astrocytes, neurons and microglia to UCB, the cascade of events implicated in the immunostimulant effects of UCB, as well as the role of each nerve cell type and maturation state in the neuropathology of UCB. Identification of the signaling events promoted by UCB will be relevant for developing novel therapies that might reduce the risk of brain injury and disabilities.

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Neuroglial activation repertoire in the injured brain: graded response, molecular mechanisms and cues to physiological function

Cited by 764 publications

References 281 publications

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

Gangliosides as apoptotic signals in ER stress response

Biological risks for neurological abnormalities associated with hyperbilirubinemia

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