A microdialysis method for the recovery of IL-1β, IL-6 and nerve growth factor from human brain in vivo

Winter, Chris; Iannotti, Fausto; Pringle, Ashley K.; Trikkas, Christos; Clough, Geraldine F.; Church, Martin K.

doi:10.1016/s0165-0270(02)00153-x

Cited by 114 publications

(87 citation statements)

References 21 publications

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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%

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%

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

2010

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“…The tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-b), IL-6, and transforming growth factor-b have been identified in the cerebrospinal fluid (CSF), plasma, or brain tissues of animals after cerebral ischemic or traumatic insults (Taupin et al, 1993;Wang et al 1995;Loddick et al, 1998;Stover et al, 2000). IL-6 production has also been demonstrated clinically, with ventricular CSF and plasma levels being elevated for days following TBI (McClain et al, 1991;Kossmann et al, 1995Kossmann et al, , 1996Aibiki et al, 1999;Csuka et al, 1999;Volkmar et al, 1999;Schwerdtfeger et al, 2001;Singhal et al, 2002;Winter et al, 2002;Buttram et al, 2007). Recent experimental and clinical studies have reported a positive correlation between IL-6 levels and injury severity and prognosis (Tarkowski et al, 1995;Juttler et al, 2002;Woiciechowsky et al, 2002;Minambres, et al, 2003;Frugier et al, 2010;Leyet et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Temporal Profile of Cerebrospinal Fluid, Plasma, and Brain Interleukin-6 After Normothermic Fluid-Percussion Brain Injury: Effect of Secondary Hypoxia

Chatzipanteli

Vitarbo

Alonso

et al. 2012

Therapeutic Hypothermia and Temperature Management

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Interleukin-6 (IL-6) is a proinflammatory cytokine that may play multiple roles in the pathogenesis of traumatic brain injury (TBI). The present study determined time-dependent changes in IL-6 concentrations in vulnerable brain regions, cerebrospinal fluid (CSF) samples, and plasma after normothermic TBI. Because secondary insults are common in head injured patients, we also assessed the consequences of a post-traumatic secondary hypoxic insult on this pleiotropic cytokine. Male Sprague-Dawley rats were intubated, anesthetized, and underwent a moderate parasagittal fluid-percussion brain injury (1.8-2.1 atm, 37°C) followed by either 30 minutes of normoxic or hypoxic (pO 2 = 30-40 mmHg) gas levels. Rats were sacrificed 3, 6, or 24 hours after TBI or shamoperated procedures. Brain samples, including the ipsilateral cerebral cortex and hippocampus were dissected and analyzed. Plasma and CSF samples were collected at similar times and stored at -80°C until analysis. IL-6 levels were significantly increased ( p < 0.05) at 3, 6, and 24 hours in the cerebral cortex and at 6 hours in the hippocampus after TBI. IL-6 levels in the TBI normoxic group for both structures returned to control levels by 24 hours. Plasma levels of IL-6 were elevated at all time points, while CSF levels were high at 3 and 6 hours, but normalized by 24 hours. Post-traumatic hypoxia led to significantly elevated ( p < 0.05) IL-6 protein levels in the cerebral cortex at 24 hours compared to sham-operated controls. These findings demonstrate that moderate TBI leads to an early increase in IL-6 brain, plasma, and CSF protein levels. Secondary post-traumatic hypoxia, a common secondary injury mechanism, led to prolonged elevations in plasma IL-6 levels that may participate in the pathophysiology of this complicated TBI model.

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“…Recovery of cytokines and neurotrophins from the ECF of the brain has been reported in patients suffering from severe TBI using cerebral microdialysis [50,51]. Although these observations are promising, we wondered whether intracerebral implantation of the microdialysis probe alone would affect cytokine production in the brain.…”

Section: Methodsmentioning

confidence: 97%

Cerebral microdialysis of interleukin (IL)-1ß and IL-6: extraction efficiency and production in the acute phase after severe traumatic brain injury in rats

Folkersma

Brevé

Tilders

et al. 2008

Acta Neurochir (Wien)

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Background As a research tool, cerebral microdialysis might be a useful technique in monitoring the release of cytokines into the extracellular fluid (ECF) following traumatic brain injury (TBI). We established extraction efficiency of Interleukin(IL)-1ß and Interleukin(IL)-6 by an in vitro microdialysis-perfusion system, followed by in vivo determination of the temporal profile of extracellular fluid cytokines after severe TBI in rats. Materials and methodsIn vitro experiments using a polyether sulfon (PES) microdialysis probe especially developed for recovery of macromolecules such as cytokines, were carried out to establish the extraction efficiency of IL-1ß and IL-6 from artificial cerebrospinal fluid (CSF) with defined IL-1ß and IL-6 concentrations. In vivo experiments in which rats were subjected to TBI or sham and microdialysis samples were collected from the parietal lobe for measurement of cytokines. Findings The extraction efficiency was maximal 6.05% (range, 5.97-6.13%) at 0.5 µl/min −1 and decreased at higher flow rates. Both cytokines were detectable in the dialysates. Highest IL-1ß levels were found within 200 min, highest IL-6 concentrations were detected at later intervals (200-400 min). No differences were found between the TBI and control groups. Conclusions Cerebral microdialysis allows measurement of cytokine secretion in the ECF of brain tissue in rats.

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A microdialysis method for the recovery of IL-1β, IL-6 and nerve growth factor from human brain in vivo

Cited by 114 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

Temporal Profile of Cerebrospinal Fluid, Plasma, and Brain Interleukin-6 After Normothermic Fluid-Percussion Brain Injury: Effect of Secondary Hypoxia

Cerebral microdialysis of interleukin (IL)-1ß and IL-6: extraction efficiency and production in the acute phase after severe traumatic brain injury in rats

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