Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue

Morganti-Kossman, M C; Lenzlinger, Philipp M.; Hans, Volkmar; Stahel, Philip F.; Csuka, Esther; Ammann, Emerita; Stocker, Reto; Trentz, O.; Kossmann, Thomas

doi:10.1038/sj.mp.4000227

Cited by 240 publications

(147 citation statements)

References 5 publications

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“…Among the acute consequences of TBI are the breakdown of the blood-brain barrier and glutamate-mediated toxicity. TNF-␣ has been suggested to participate in blood-brain barrier breakdown after TBI (4,10,42). TNF-␣ modulates capillary permeability by inducing the transcription of proteolytic enzymes, which may result in increased blood-brain barrier permeability and increased vasogenic brain edema (43).…”

Section: Discussionmentioning

confidence: 99%

“…Tumor necrosis factor ␣ (TNF-␣), one of the central mediators of tissue injury and inflammation, has been implicated in the pathogenesis of several central nervous system disorders including cerebral ischemia, Parkinson's disease, and brain trauma (1)(2)(3)(4). In patients with ischemic brain damage, concentrations of TNF in peripheral blood have been correlated with brain lesion volume and associated with poor functional and neurological outcome (5).…”

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confidence: 99%

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Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

Scherbel

Raghupathi

Nakamura

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

377

231

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The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(؊/؊)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(؊/؊), n ‫؍‬ 10; wt, n ‫؍‬ 10] or served as uninjured controls [TNF(؊/؊), n ‫؍‬ 10; wt, n ‫؍‬ 10] and were evaluated for deficits in memory retention at 7 days postinjury. Although both brain-injured wt and TNF(؊/؊) mice exhibited significant memory dysfunction compared to uninjured controls (P < 0.02), the deficits in memory retention in injured TNF(؊/؊) mice were significantly less severe than in injured wt mice (P < 0.02). A second group of mice was subjected to CCI brain injury [TNF(؊/؊), n ‫؍‬ 20; wt, n ‫؍‬ 20] or served as uninjured controls [TNF(؊/؊), n ‫؍‬ 15; wt, n ‫؍‬ 15] and were evaluated over a 4-week period for neurological motor function. In the acute posttraumatic period (48 h postinjury), braininjured TNF(؊/؊) mice were significantly less impaired than injured wt mice on composite neuroscore (P < 0.001), rotarod (P < 0.05), and beam balance (P < 0.02) tests. However, wt mice recovered from brain injury by 2-3 weeks postinjury, whereas TNF(؊/؊) mice continued to demonstrate persistent motor deficits up to 4 weeks postinjury. Histopathological analysis at 2 and 4 weeks postinjury revealed that brain-injured TNF(؊/؊) mice had significantly more cortical tissue loss than wt mice (P < 0.02). Our results suggest that although the presence of TNF in the acute posttraumatic period may be deleterious, this cytokine may play a role in facilitating long-term behavioral recovery and histological repair after brain injury.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

Scherbel

Raghupathi

Nakamura

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

377

231

View full text Add to dashboard Cite

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“…78 In addition, our group showed that maximal concentrations of IL-8 in human CSF were associated with severe BBB disruption; however, the ability of IL-8 to stimulate nerve growth factor production from cultured mouse astrocytes implies some neurotrophic properties of this chemokine. 79 …”

Section: Interleukin-8/macrophage Inflammatory Protein-2mentioning

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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“…Thus, in addition to primary parenchymal changes in cytokine levels and expression, TBI can also produce systemic alterations that may influence brain vulnerability and outcome. For example, experimental and clinical studies have measured circulating cytokines and chemokines in blood and cerebrospinal fluid (CSF) samples after trauma (Morganti-Kossman et al, 1997). In a clinical study of pediatric brain trauma, a positive correlation between plasma and CSF levels of IL1-β and injury severity as measured by the Glasgow Coma Scale and Outcome Score was reported (Chiaretti et al, 2005).…”

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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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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Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue

Cited by 240 publications

References 5 publications

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

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

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

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