Acute brain trauma, lung injury, and pneumonia: more than just altered mental status and decreased airway protection

Abstract

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Even when patients survive the initial insult, there is significant morbidity and mortality secondary to subsequent pulmonary edema, acute lung injury (ALI), and nosocomial pneumonia. Whereas the relationship between TBI and secondary pulmonary complications is recognized, little is known about the mechanistic interplay of the two phenomena. Changes in mental status secondary to acute brain injury certainly impair airway- and lung-protective mechanisms. However, clinical and translational evidence suggests that more specific neuronal and cellular mechanisms contribute to impaired systemic and lung immunity that increases the risk of TBI-mediated lung injury and infection. To better understand the cellular mechanisms of that immune impairment, we review here the current clinical data that support TBI-induced impairment of systemic and lung immunity. Furthermore, we also review the animal models that attempt to reproduce human TBI. Additionally, we examine the possible role of damage-associated molecular patterns, the chlolinergic anti-inflammatory pathway, and sex dimorphism in post-TBI ALI. In the last part of the review, we discuss current treatments and future pharmacological therapies, including fever control, tracheostomy, and corticosteroids, aimed to prevent and treat pulmonary edema, ALI, and nosocomial pneumonia after TBI.

Innate immune responses to trauma

“…High concentrations of glutamate derived from neurons and glia after TBI cause a switch from anti-inflammatory signaling to pro-inflammatory signaling in peripheral leukocytes in response to ATP and adenosine, which results in ‘neurogenic ALI’ 133 . Furthermore, TBI increases the recruitment of neutrophils to the bronchoalveolar space, but it can also suppress the pulmonary immune response via the cholinergic anti-inflammatory pathway, which puts the lungs at an enhanced risk of infection 134 .…”

Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia

“…Clinical data have revealed a link between brain injury and lung inflammation [4, 34]. Kalsotra and colleagues [15] provided the first experimental evidence that brain injury directs pulmonary neutrophil mobilisation.…”

Decoding inflammation, its causes, genomic responses, and emerging countermeasures

“…Redness and swelling (see Figure ) represent the vasodilation and increased vascular permeability responsible for microvascular leaks. Brain and lung oedema are the most severe forms of microvascular leaks . Small blood vessels (<100 μm in diameter) comprising the microcirculation of multiple organs are primarily affected by microbial, autoimmune and allergic inflammation.…”

“…Brain and lung oedema are the most severe forms of microvascular leaks. 285 Small blood vessels (<100 μm in diameter) comprising the microcirculation of multiple organs are primarily affected by microbial, autoimmune and allergic inflammation. The end stage of microbial inflammation, sepsis and septic shock, represents severe endothelial dysfunction, causing the reversible or irreversible injury to microcirculation which is responsible for multiple organ failure.…”