Limits...
Bench-to-bedside review: Burn-induced cerebral inflammation--a neglected entity?

Flierl MA, Stahel PF, Touban BM, Beauchamp KM, Morgan SJ, Smith WR, Ipaktchi KR - Crit Care (2009)

Bottom Line: Severe burn injury remains a major burden on patients and healthcare systems.If the blood-brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system.Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopaedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, CO 80204, USA. michael.flierl@dhha.org

ABSTRACT
Severe burn injury remains a major burden on patients and healthcare systems. Following severe burns, the injured tissues mount a local inflammatory response aiming to restore homeostasis. With excessive burn load, the immune response becomes disproportionate and patients may develop an overshooting systemic inflammatory response, compromising multiple physiological barriers in the lung, kidney, liver, and brain. If the blood-brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system. Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema. Despite the correlation between cerebral complications in severe burn victims with mortality, burn-induced neuroinflammation continues to fly under the radar as an underestimated entity in the critically ill burn patient. In this paper, we illustrate the molecular events leading to blood-brain barrier breakdown, with a focus on the subsequent neuroinflammatory changes leading to cerebral edema in patients with severe burns.

Show MeSH

Related in: MedlinePlus

Pathophysiological events resulting in blood–brain barrier breakdown and development of cerebral edema following burn injury. Following major burn trauma, a robust systemic inflammatory response is triggered. Proinflammatory mediators are produced by various immune cells, resulting in breakdown of the blood–brain barrier, with subsequent activation of resident central nervous system cells, such as microglia and astrocytes, which respond with further production of inflammatory markers, cumulating in a massive neuroinflammatory response and subsequent life-threatening cerebral edema. In parallel, significant hormonal changes are triggered, resulting in a severe hypermetabolic state. CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic hormone.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2717412&req=5

Figure 2: Pathophysiological events resulting in blood–brain barrier breakdown and development of cerebral edema following burn injury. Following major burn trauma, a robust systemic inflammatory response is triggered. Proinflammatory mediators are produced by various immune cells, resulting in breakdown of the blood–brain barrier, with subsequent activation of resident central nervous system cells, such as microglia and astrocytes, which respond with further production of inflammatory markers, cumulating in a massive neuroinflammatory response and subsequent life-threatening cerebral edema. In parallel, significant hormonal changes are triggered, resulting in a severe hypermetabolic state. CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic hormone.

Mentions: These events cause subsequent neuronal damage [16] and cerebral edema [17,18], and can result in critically increased intracranial pressure [19]. The pathophysiological events leading to this severe inflammatory downward spiral are depicted in Figure 2. The extent of BBB leakage following severe burn seems to correlate with mortality in severe burn victims [5]. In the following sections, we illustrate the molecular mechanisms involved in BBB failure.


Bench-to-bedside review: Burn-induced cerebral inflammation--a neglected entity?

Flierl MA, Stahel PF, Touban BM, Beauchamp KM, Morgan SJ, Smith WR, Ipaktchi KR - Crit Care (2009)

Pathophysiological events resulting in blood–brain barrier breakdown and development of cerebral edema following burn injury. Following major burn trauma, a robust systemic inflammatory response is triggered. Proinflammatory mediators are produced by various immune cells, resulting in breakdown of the blood–brain barrier, with subsequent activation of resident central nervous system cells, such as microglia and astrocytes, which respond with further production of inflammatory markers, cumulating in a massive neuroinflammatory response and subsequent life-threatening cerebral edema. In parallel, significant hormonal changes are triggered, resulting in a severe hypermetabolic state. CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic hormone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2717412&req=5

Figure 2: Pathophysiological events resulting in blood–brain barrier breakdown and development of cerebral edema following burn injury. Following major burn trauma, a robust systemic inflammatory response is triggered. Proinflammatory mediators are produced by various immune cells, resulting in breakdown of the blood–brain barrier, with subsequent activation of resident central nervous system cells, such as microglia and astrocytes, which respond with further production of inflammatory markers, cumulating in a massive neuroinflammatory response and subsequent life-threatening cerebral edema. In parallel, significant hormonal changes are triggered, resulting in a severe hypermetabolic state. CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic hormone.
Mentions: These events cause subsequent neuronal damage [16] and cerebral edema [17,18], and can result in critically increased intracranial pressure [19]. The pathophysiological events leading to this severe inflammatory downward spiral are depicted in Figure 2. The extent of BBB leakage following severe burn seems to correlate with mortality in severe burn victims [5]. In the following sections, we illustrate the molecular mechanisms involved in BBB failure.

Bottom Line: Severe burn injury remains a major burden on patients and healthcare systems.If the blood-brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system.Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopaedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, CO 80204, USA. michael.flierl@dhha.org

ABSTRACT
Severe burn injury remains a major burden on patients and healthcare systems. Following severe burns, the injured tissues mount a local inflammatory response aiming to restore homeostasis. With excessive burn load, the immune response becomes disproportionate and patients may develop an overshooting systemic inflammatory response, compromising multiple physiological barriers in the lung, kidney, liver, and brain. If the blood-brain barrier is breached, systemic inflammatory molecules and phagocytes readily enter the brain and activate sessile cells of the central nervous system. Copious amounts of reactive oxygen species, reactive nitrogen species, proteases, cytokines/chemokines, and complement proteins are being released by these inflammatory cells, resulting in additional neuronal damage and life-threatening cerebral edema. Despite the correlation between cerebral complications in severe burn victims with mortality, burn-induced neuroinflammation continues to fly under the radar as an underestimated entity in the critically ill burn patient. In this paper, we illustrate the molecular events leading to blood-brain barrier breakdown, with a focus on the subsequent neuroinflammatory changes leading to cerebral edema in patients with severe burns.

Show MeSH
Related in: MedlinePlus