Early neuronal expression of tumor necrosis factor-α after experimental brain injury contributes to neurological impairment

Knoblach, Susan M.; Fan, Lei; Faden, Alan I.

doi:10.1016/s0165-5728(98)00273-2

Cited by 243 publications

(148 citation statements)

References 51 publications

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“…First pro-inflammatory cytokines appear to block the analgesic effects of opioids [41,42], which may explain the decreased efficacy of morphine in Experiment 1. Second, pro-inflammatory cytokines have been linked to cytotoxic effects in the nervous system [43,44,45]. Yang et al [36] suggest that there is a critical balance between beneficial and toxic effects that depends on cytokine concentrations.…”

Section: Discussionmentioning

confidence: 99%

The impact of morphine after a spinal cord injury

Hook

Liu

Washburn

et al. 2007

Behavioural Brain Research

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Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury.

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Section: Discussionmentioning

confidence: 99%

The impact of morphine after a spinal cord injury

Hook

Liu

Washburn

et al. 2007

Behavioural Brain Research

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“…Of particular interest to the development of an animal model of PTH, the lateral FP model of TBI was shown to produce a pathologic neurotransmitter response in the hypothalamus (McIntosh et al, 1994). After lateral FP brain injury, there is evidence of histopathologic damage in the cortex, thalamus, and hippocampal regions (Soares et al, 1995;Hicks et al, 1996;Bramlett et al, 1997;Pierce et al, 1998;Bramlett and Dietrich, 2002), and regional inflammatory changes including astrocytosis and microglia/macrophage infiltration (Soares et al, 1995;Aihara et al, 1995;Hill et al, 1996;Knoblach et al, 1999;Hill-Felberg et al, 1999). A large percentage of severely brain-injured animals (70%) could not adequately thermoregulate for up to 24 hours after injury and became hypothermic despite maintenance of normothermia during surgical procedures.…”

Section: Discussionmentioning

confidence: 99%

Development of Posttraumatic Hyperthermia after Traumatic Brain Injury in Rats is Associated with Increased Periventricular Inflammation

Thompson

Hoover

Tkacs

et al. 2005

J Cereb Blood Flow Metab

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Posttraumatic hyperthermia (PTH) is a noninfectious elevation in body temperature that negatively influences outcome after traumatic brain injury (TBI). We sought to (1) characterize a clinically relevant model and (2) investigate potential cellular mechanisms of PTH. In study I, body temperature patterns were analyzed for 1 week in male rats after severe lateral fluid percussion (FP) brain injury (n ¼ 75) or sham injury (n ¼ 17). After injury, 27% of surviving animals experienced PTH, while 69% experienced acute hypothermia with a slow return to baseline. A profound blunting or loss of circadian rhythmicity (CR) that persisted up to 5 days after injury was experienced by 75% of brain-injured animals. At 2 and 7 days after injury, patterns of cell loss and inflammation were assessed in selected brain thermoregulatory and circadian centers. Significant cell loss was not observed, but PTH was associated with inflammatory changes in the hypothalamic paraventricular nucleus (PVN) by one week after injury. In brain-injured animals with altered CR, reactive astrocytes were bilaterally localized in the suprachiasmatic nucleus (SCN) and the PVN. Occasional IL-1b þ / ED-1 þ macrophages/microglia were observed in the PVN and SCN exclusively in brain-injured animals developing PTH. In animals with PTH there was a significant positive correlation (r ¼ 0.788, Po0.01) between the degree of postinjury hyperthermia and the total number of cells positive for inflammatory markers within selected thermoregulatory and circadian nuclei. In study II, a separate group of animals underwent the same injury and temperature monitoring paradigm as in study I, but had additional physiologic data obtained, including vital signs, arterial blood gases, white blood cell counts, and C-reactive protein levels. All parameters remained within normal ranges after injury. These data suggest that PTH and the alteration in CR of temperature may be due, in part, to acute reactive astrocytosis and inflammation in hypothalamic centers responsible for both thermoregulation and CR.

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“…Studies on rat models of focal TBI have demonstrated that TNF is upregulated in the brain within a few hours of trauma. 35,36,54 The contribution of TNF to tissue damage has been reported in animal studies, whereby recombinant TNF injected into the brain induced cerebral inflammation, breakdown of the BBB, and intracranial leukocyte recruitment. 55,56 Shohami et al 51 analyzed three different compounds, dexanabinol (HU-211), TNF-binding protein and pentoxifylline (PTX), for their effectiveness in inhibiting TNF transcription and bioactivity following closed head injury in rats.…”

Section: Tumor Necrosis Factor-␣mentioning

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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Early neuronal expression of tumor necrosis factor-α after experimental brain injury contributes to neurological impairment

Cited by 243 publications

References 51 publications

The impact of morphine after a spinal cord injury

The impact of morphine after a spinal cord injury

Development of Posttraumatic Hyperthermia after Traumatic Brain Injury in Rats is Associated with Increased Periventricular Inflammation

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

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