Interleukin-1 receptor antagonist inhibits neuronal damage caused by fluid percussion injury in the rat

Toulmond, Sylvie; Rothwell, Nancy J.

doi:10.1016/0006-8993(94)01343-g

Cited by 233 publications

(126 citation statements)

References 24 publications

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“…Although, IL-1 receptor protein levels were not measured in the present study, IL-1r1 mRNA levels were still elevated at day 3 post-TBI indicating the potential for continuous upregulation of IL-1 receptor for activation. As previously discussed, therapies including the administration of the endogenous IL-1r1 antagonist have been reported to protect against neuronal injury after FP brain injury (Sanderson et al, 1999, Toulmond andRothwell, 1995), controlled cortical impact injury (Tehranian et al, 2002), and cerebral ischemia (McColl et al, 2007, Relton andRothwell, 1992). These treatment strategies have primarily targeted endogenous sources of IL-1β that have been proposed to increase neuronal vulnerability and worsen behavioral outcome.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the proinflammatory cytokine interleukin-1β (IL-1β) is induced rapidly after TBI (Fassbender et al, 2000, Kinoshita et al, 2002, Taupin et al, 1993, and released by both activated astrocytes and microglia. Previously, strategies that target IL-1β, including the administration of anti-cytokine agents including the naturally-occurring interleukin-1 receptor antagonist (IL-1RA) have been reported to reduce damage caused by TBI (Sanderson et al, 1999, Taupin et al, 1993, Tehranian et al, 2002, Toulmond and Rothwell, 1995.…”

Section: Introductionmentioning

confidence: 99%

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Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats

Utagawa

Truettner

Dietrich

et al. 2008

Experimental Neurology

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The proinflammatory cytokine interleukin-1β (IL-1β) is induced rapidly after traumatic brain injury (TBI) and contributes to the inflammatory events that lead to neuronal loss. Although an important source of IL-1β is from the injured brain itself, in patients with multiple organ trauma (polytrauma) IL-1β is also released into the bloodstream which may potentially influence brain vulnerability. The purpose of this study was to determine the effects of systemic inflammation induced by peripheral administration of IL-1β on histopathological and behavioral outcome after moderate fluid percussion (FP) brain injury in rats. At 30 min or 24 hr after TBI, saline, 20μg/kg or 40μg/kg of IL-1β was injected (n=4-9/group) intraperitoneally (IP). Sham operated animals (n=9) received either saline or IL-1β (20 or 40 μg/kg) injections. The somatosensory tactile placing test was administered at 1, 2 and 3 days posttrauma. IL-1β treated animals showed significant placing deficits compared to vehicle-treated TBI animals. Three days after injection, contusion areas and volumes were significantly increased (p<0.05) with both IL-1β doses and at both treatment times compared to vehicle treated animals. IL-1β treated rats showed more contusion injury and hippocampal neuronal damage as well as enhanced perivascular neutrophil accumulation. Cortical IL-1r1 mRNA increased as early as 1 hr following TBI, peaking at 24 hr and remained elevated 3 days posttrauma. These data show that the posttraumatic administration of IL-1β significantly aggravates behavioral outcome and increases overall contusion volume after TBI. Increased systemic inflammatory processes, including extravasation of activated leukocytes and proinflammatory cytokines could participate in this detrimental outcome. Because peripherally circulating cytokines and other neurotoxic factors may be increased following multi-organ trauma, these findings may be important in targeting therapeutic interventions in this patient population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats

Utagawa

Truettner

Dietrich

et al. 2008

Experimental Neurology

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“…Many studies have shown the protective effects ofIL-I ra in brain injury. Thus, intracerebroventricular administra tion of recombinant IL-lra produced a marked reduction in brain damage induced by focal stroke (Reiton et aI., 1996;Rothwell and Relton, 1993;Loddick and Rothwell, 1996), brain hypoxia-ischemia (Martin et aI., 1995), or fluid percussion injury in the rat (Toulmond and Rothwell, 1995). This neuronal protective effect of IL-I ra in focal stroke was further supported by a recent study using an adenoviral vector that overexpressed IL-1 ra in the brain (Betz et aI., 1995).…”

Section: Neuroprotection By Cytokine Inhibition Supports Anti·inflammmentioning

confidence: 99%

Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics

Barone

Feuerstein

1999

J Cereb Blood Flow Metab

864

610

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Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support for this hypothesis has been drawn from many studies where neutrophil-depletion blockade of endothelial-leukocyte interactions has been achieved by various techniques. The inflammation reaction is an attractive pharmacologic opportunity, considering its rapid initiation and progression over many hours after stroke and its contribution to evolution of tissue injury. While the expression of inflammatory cytokines that may contribute to ischemic injury has been repeatedly demonstrated, cytokines may also provide “neuroprotection” in certain conditions by promoting growth, repair, and ultimately, enhanced functional recovery. Significant additional basic work is required to understand the dynamic, complex, and time-dependent destructive and protective processes associated with inflammation mediators produced after brain injury. The realization that brain ischemia and trauma elicit robust inflammation in the brain provides fertile ground for discovery of novel therapeutic agents for stroke and neurotrauma. Inhibition of the mitogen-activated protein kinase (MAPK) cascade via cytokine suppressive anti-inflammatory drugs, which block p38 MAPK and hence the production of interleukin-1 and tumor necrosis factor-α, are most promising new opportunities. However, spatial and temporal considerations need to be exercised to elucidate the best opportunities for selective inhibitors for specific inflammatory mediators.

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“…IL-1ra binds to both type I and type II IL-1 receptors, partially blocking cellular responses mediated by IL-1a and IL-1b (Loddick et al, 1997). In the rat fluid percussion injury (FPI) model, 10 lg of intracerebroventricular IL-1ra, administered 15 min and 2, 4, 6, 8, 24, and 48 h after injury significantly reduced lesion size (Toulmond and Rothwell, 1995). An increase in the IL-1ra expression has been proposed as a mechanism for the anti-inflammatory and neuroprotective effect of estrogen in hippocampal slice studies (Choi et al, 2008).…”

mentioning

confidence: 99%

The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

Anderson

Farin

Bammler

et al. 2011

Journal of Neurotrauma

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Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10 mg/kg or 20 mg/kg given i.p.) was started 4 h post-injury and administered every 12 h post-injury for up to 72 h, with the last injection 12 hr prior to death for the 24 h and 72 h groups. In the CCI-injured vehicle group compared to non-injured animals, expression of 1,114, 4,229, and 291 distinct genes changed > 1.5-fold ( p < 0.05) at 24 h, 72 h, and 7 days, respectively. At 24 h, the effect of low-dose progesterone on differentially expressed genes was < 20% the effect of higher dose compared to vehicle. GO analysis identified a significant effect of low-and high-dose progesterone treatment compared to vehicle on DNA damage response. At 72 h, high-dose progesterone treatment compared to vehicle affected expression of almost twice as many genes as did low-dose progesterone. Both low-and high-dose progesterone resulted in expression of genes regulating inflammatory response and apoptosis. At 7 days, there was only a modest difference in high-dose progesterone compared to vehicle, with only 14 differentially expressed genes. In contrast, low-dose progesterone resulted in 551 differentially expressed genes compared to vehicle. GO analysis identified genes for the low-dose treatment involved in positive regulation of cell proliferation, innate immune response, positive regulation of anti-apoptosis, and blood vessel remodeling.

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Interleukin-1 receptor antagonist inhibits neuronal damage caused by fluid percussion injury in the rat

Cited by 233 publications

References 24 publications

Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats

Systemic inflammation exacerbates behavioral and histopathological consequences of isolated traumatic brain injury in rats

Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics

The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

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