Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production

Woodroofe, Nicola; Sarna, G. S.; Wadhwa, Meenu; Hayes, G. M.; Loughlin, Jane; Tinker, Andrew; Cuzner, M. L.

doi:10.1016/0165-5728(91)90110-s

Cited by 538 publications

(255 citation statements)

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“…Elevated IL-1␤ has been detected in the CSF and brain parenchyma within the early hours after brain injury in both humans and rodents. 23,24 Treatment of TBI rats with either endogenous IL-1ra or soluble IL-1 receptors conferred no improvement in motor outcome. 25 Nonetheless, IL-1 has been documented to play a role in neuronal degeneration.…”

Section: Interleukin-1mentioning

confidence: 99%

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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-1mentioning

confidence: 99%

“…34 Interleukin-6 has also been detected in brain tissue in several experimental models of TBI. 24,35,36 Studies using BBB ϭ blood-brain barrier; HU-211 ϭ dexanabinol; PTX ϭ pentoxifylline; TBI ϭ traumatic brain injury. *Corresponding to the rodent homolog macrophage inflammatory protein-2 (MIP-2).…”

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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“…In cases such as cerebral ischaemia and excitotoxic brain injury, IL-1b levels dramatically increase in the brain within few hours (Minami et al 1991;Woodroofe et al 1991;Taupin et al 1993), and several studies have shown that inhibition or gene disruption of the Received March 12, 2002; revised manuscript received July 18, 2002; accepted August 19, 2002. Address correspondence and reprint requests to Anastasia Simi, Institute for Environmental Medicine, Division of Molecular Toxicology, Karolinska Institute, S-171 77 Stockholm, Sweden.…”

Section: Introductionmentioning

confidence: 99%

The neuroprotective agents chlomethiazole and SB203580 inhibit IL‐1β signalling but not its biosynthesis in rat cortical glial cells

Simi

Porsmyr-Palmertz

Hjertén

et al. 2002

Journal of Neurochemistry

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Chlomethiazole and pyridinyl imidazole compounds, exemplified by SB203580, are structurally distinct p38 mitogenactivated protein kinase inhibitors with neuroprotective properties in models of cerebral ischaemia. We have examined their effects in interleukin-1b (IL-1b) synthesis, release and signalling in rat cortical glial cells, given the important role of IL-1b in cerebral ischaemia. We analysed (i) IL-1b mRNA expression by northern blot, (ii) IL-1b protein precursor levels within the cells by western blot, and (iii) the levels of the mature IL-1b protein secreted into the medium by enzymelinked immunosorbent assay (ELISA) after treatment of rat cortical glial cells with lipopolysaccharide. While the induction of IL-1b expression by lipopolysaccharide or by IL-1b itself was very sensitive to nuclear factor kappa B (NF-jB) inhibitors, chlomethiazole or SB203580 were nearly without effect, indicating a differential regulation as compared to peripheral cells, e.g. monocytes. In contrast, chlomethiazole and SB203580 potently inhibited the IL-1b-induced expression of c-fos and inducible nitric oxide synthase, as monitored by northern blot and quantitative RT-PCR, respectively. Because IL-1b-induced expression of c-fos and inducible nitric oxide synthase is believed to directly contribute to the pathology of cerebral ischaemic injury, the results suggest a direct mechanism for the neuroprotective effects of chlomethiazole and SB203580, and further establish the anti-inflammatory properties of chlomethiazole. Keywords: chlomethiazole, glia, interleukin-1b, neuroprotection, p38 MAP kinase. Interleukin-1b (IL-1b) is a pro-inflammatory cytokine which is released by a variety of cell types, including peripheral immune cells as well as cells of the CNS-like astrocytes, microglia and some neurones (Dinarello 1988;Hopkins and Rothwell 1995). It serves a broad array of functions both in the periphery and in the CNS, and is involved in the immune-to-brain communication initiating the so-called Ôsickness responseÕ, such as the induction of fever in response to an invasion by a pathogen (for review see Rothwell 1997).Within the CNS, IL-1b is increased in response to brain injury and subsequently regulates the brain's inflammatory response by stimulating the production of other cytokines, such as IL-6 and IL-8, as well as inducible nitric oxide synthase (iNOS), chemotactic factors and adhesion molecules, for attracting peripheral mononuclear cells to cross the blood-brain barrier (Benveniste et al. 1990;Yamasaki et al. 1995;. In cases such as cerebral ischaemia and excitotoxic brain injury, IL-1b levels dramatically increase in the brain within few hours (Minami et al. 1991;Woodroofe et al. 1991;Taupin et al. 1993), and several studies have shown that inhibition or gene disruption of the Received March 12, 2002; revised manuscript received July 18, 2002; accepted August 19, 2002. Address correspondence and reprint requests to Anastasia Simi, Institute for Environmental Medicine, Division of Molecular Toxicology, Karo...

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“…Existing literature demonstrates that after trauma changes in mRNA correlate with changes in protein expression and, therefore, changes documented in the current study will probably reflect changes at the protein level as well. For example, upregulation of message and protein are correlated after brain injury for NGF, 13,23 glial fibrillary acidic protein, 49 S100b, 30 basic fibroblast growth factor, 33,75 TNF-a, IL-6, IL-1b, 18,19,31,60,63,67 c-fos, c-jun, junB and zif-286. 32,54,72 An understanding of these transcriptional changes may suggest future therapeutic strategies for brain-injured patients specifically targeted at augmenting beneficial or blunting detrimental, endogenous, post-injury response mechanisms with the ultimate goal of minimizing the resultant progression of damage.…”

Section: Discussionmentioning

confidence: 99%

Traumatic injury induces differential expression of cell death genes in organotypic brain slice cultures determined by complementary DNA array hybridization

et al. 2000

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Abstract-The expression of a large panel of selected genes hypothesized to play a central role in post-traumatic cell death was shown to be differentially altered in response to a precisely controlled, mechanical injury applied to an organotypic slice culture of the rat brain. Within 48 h of injury, the expression of nerve growth factor messenger RNA was significantly increased whereas the levels of bcl-2, a-subunit of calcium/calmodulin-dependent protein kinase II, cAMP response element binding protein, 65,000 mol. wt isoform of glutamate decarboxylase, 1b isoform of protein kinase C, and ubiquitin messenger RNA were significantly decreased. Because the expression levels of a number of other messenger RNAs such as the neuron-specific amyloid precursor protein, b 2 microglobulin, bax, bcl xl , brain-derived neurotrophic factor, cyclooxygenase-2, interleukin-1b, interleukin-6, tumor necrosis factor-a, receptor tyrosine kinase A, and receptor tyrosine kinase B were unaffected, these selective changes may represent components of an active and directed response of the brain initiated by mechanical trauma.Interpretation of these co-ordinated alterations suggests that mechanical injury to the central nervous system may lead to disruption of calcium homeostasis resulting in altered gene expression, an impairment of intracellular cascades responsible for trophic factor signaling, and initiation of apoptosis via multiple pathways. An understanding of these transcriptional changes may contribute to the development of novel therapeutic strategies to enhance beneficial and blunt detrimental, endogenous, post-injury response mechanisms. ᭧ 2000 IBRO. Published by Elsevier Science Ltd.Key words: genomic expression, in vitro model, traumatic brain injury, organotypic culture, stretch injury, cDNA array.The primary mechanical event associated with traumatic injury to the CNS initiates a cascade of molecular and cellular events which include changes in gene expression, culminating in cell dysfunction and/or death. Although the initial injury occurs in less than 1 s, the post-traumatic sequelae may take hours or days to develop, thereby providing an opportunity to therapeutically attenuate detrimental or augment beneficial endogenous responses in an attempt to limit resultant cell death. A detailed analysis of these specific molecular events may aid in the rational development of novel therapies for the brain-injured patient. Many genes which have been reported to be up-regulated following experimental models of traumatic brain injury (TBI), such as c-fos, c-jun, junB or zif/ 268, 24,54,58,69 are transcription factors that control the expression of other genes, suggesting that the expression of a large number of genes, including those involved in cell death or survival, may be affected by trauma.In this regard, expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), necessary for neuronal and other cell survival, has been shown to be increased after controlled cortical impact (CCI) injury in the rat. ...

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Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production

Cited by 538 publications

References 21 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

The neuroprotective agents chlomethiazole and SB203580 inhibit IL‐1β signalling but not its biosynthesis in rat cortical glial cells

Traumatic injury induces differential expression of cell death genes in organotypic brain slice cultures determined by complementary DNA array hybridization

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