Transcranial cytokine gradients in patients requiring intensive care after acute brain injury

McKeating, E. G.; Andrews, Pjd; Signorini, D. F.; Mascia, Luciana

doi:10.1093/bja/78.5.520

Cited by 145 publications

(99 citation statements)

References 23 publications

(12 reference statements)

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“…In the study conducted by Kossmann et al (1997), there was no association between mortality and plasma IL-8 concentration. Similar results were published by McKeating et al (1997) who found that plasma IL-8 level was not elevated in patients with TBI. On the contrary, the recent study by Mussack et al (2002) revealed that high IL-8 plasma level after TBI may be correlated with unfavorable neurological outcome.…”

Section: Discussionsupporting

confidence: 90%

Plasma Interleukin-8 as a Potential Predictor of Mortality in Adult Patients with Severe Traumatic Brain Injury

Gopčević

Mazul-Sunko

Marout

et al. 2007

Tohoku J. Exp. Med.

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Section: Discussionsupporting

confidence: 90%

Plasma Interleukin-8 as a Potential Predictor of Mortality in Adult Patients with Severe Traumatic Brain Injury

Gopčević

Mazul-Sunko

Marout

et al. 2007

Tohoku J. Exp. Med.

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“…Therefore, we conclude that the AJ gradient is a poor gauge of intracerebral cytokine production, as previous studies have also struggled to show a reliable AJ gradient for cytokines known to be expressed after TBI. For example, McKeating et al (1997) could only show an AJ difference for IL6 but not for IL1b, IL8, and tumour necrosis factor, whereas Goodman et al (2008) found no overt AJ differences for IL1b, IL6, IL8, IL10, IL12, and tumour necrosis factor.…”

Section: Compartmentalisation Of Cytokine Productionmentioning

confidence: 90%

The Cytokine Response to Human Traumatic Brain Injury: Temporal Profiles and Evidence for Cerebral Parenchymal Production

Helmy

Carpenter

Menon

et al. 2010

J Cereb Blood Flow Metab

293

318

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The role of neuroinflammation is increasingly being recognised in a diverse range of cerebral pathologies, including traumatic brain injury (TBI). We used cerebral microdialysis and paired arterial and jugular bulb plasma sampling to characterise the production of 42 cytokines after severe TBI in 12 patients over 5 days. We compared two microdialysis perfusates in six patients: central nervous system perfusion fluid and 3.5% human albumin solution (HAS); 3.5% HAS has a superior fluid recovery (95.8 versus 83.3%), a superior relative recovery in 18 of 42 cytokines (versus 8 of 42), and a qualitatively superior recovery profile. All 42 cytokines were recovered from the human brain. Sixteen cytokines showed a stereotyped temporal peak, at least twice the median value for that cytokine over the monitoring period; day 1: tumour necrosis factor, interleukin (IL)7, IL8, macrophage inflammatory protein (MIP)1a, soluble CD40 ligand, GRO, IL1b, platelet derived growth factor (PDGF)-AA, MIP1b, RANTES; day 2: IL1 receptor antagonist (ra). IL6, granulocyte-colony stimulating factor (G-CSF), chemokine CXC motif ligand 10 (IP10); days 4 to 5: IL12p70, IL10. Brain extracellular fluid concentrations were significantly higher than plasma concentrations for 19 cytokines: basic fibroblast growth factor (FGF2), G-CSF, IL1a, IL1b, IL1ra, IL3, IL6, IL8, IL10, IL12p40, IL12p70, IP10, monocyte chemotactic protein (MCP)1, MCP3, MIP1a, MIP1b, PDGF-AA, transforming growth factor (TGF)a and vascular endothelial growth factor. No clear arterio-jugular venous gradients were apparent. These data provide evidence for the cerebral production of these cytokines and show a stereotyped temporal pattern after TBI.

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“…Central inflammation is often accompanied by the migration of peripheral inflammatory cells into the brain (57,58). After hypoxic injury, up-regulation of the adhesion molecules vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), and E-selectin on cerebrovascular endothelial cells can be inhibited by indomethacin (92,93).…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury

Gopez¹,

Yue²,

Vasudevan³

et al. 2005

Neurosurgery

104

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OBJECTIVE-Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2( 5 H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model. METHODS-DFU NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript RESULTS-DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E 2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injuryinduced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3-immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3-immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuro-protective endocannabinoid, in the injured brain.CONCLUSION-These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials.Keywords 2-Arachidonoyl glycerol; Caspase-3; COX2 inhibitor; Eicosanoids; Endocannabinoid; Neuroinflammation; Rat behavior Traumatic brain injury (TBI) initiates a central inflammatory response that results in the increased production of prostaglandins and reactive oxygen species. These products may cause secondary insults to the brain (55,90,94). Cyclooxygenases catalyze the first step in the formation of prostaglandins from arachidonic acid, producing reactive oxygen species in the process. Cyclooxygenase-1 (COX1), present normally in most tissues, is thought to maintain essential physiological functions, such as gastric mucosal integrity, renal function, and platelet homeostasis (87,101). COX2, the inducible isoform, is expressed in the normal brain (30,87) but is rare or absent in most organs under normal conditions. As in the periphery (32,79), COX2 in the brain can be regulated by inflammatory cytokines (87), and prostaglandin production increases in response to pathological conditions of the central nervous system (3,70,72,89,107). ...

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Transcranial cytokine gradients in patients requiring intensive care after acute brain injury

Cited by 145 publications

References 23 publications

Plasma Interleukin-8 as a Potential Predictor of Mortality in Adult Patients with Severe Traumatic Brain Injury

Plasma Interleukin-8 as a Potential Predictor of Mortality in Adult Patients with Severe Traumatic Brain Injury

The Cytokine Response to Human Traumatic Brain Injury: Temporal Profiles and Evidence for Cerebral Parenchymal Production

Cyclooxygenase-2-specific Inhibitor Improves Functional Outcomes, Provides Neuroprotection, and Reduces Inflammation in a Rat Model of Traumatic Brain Injury

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