the study by quilez and colleagues   in this issue of critical care reports morpho - functional and biochemical effects of mechanical ventilation with lower ( 8 ml / kg ) and higher ( 30 ml / kg ) tidal volume ( vt ) on lung and brain in healthy rats . mechanical ventilation may have a serious impact on lung structure and function , leading to ventilator - associated lung injury ( vali ) as well as promoting damage of peripheral organs , including the brain . in this respect , mechanical ventilation and sedation in healthy and diseased lungs have been reported to be associated with neurologic impairment , memory , and cognitive dysfunction . on the other hand , brain injury may enhance lung damage in experimental settings , probably by promoting a higher rate of pulmonary complications as well as by altering neurologic outcome . overall , the information in regard to the multiplepathway cross - talk between the brain and lungs is quite limited . in the study by quilez and colleagues , different variables , including lung function , plasma , and lung levels of cytokines as well as c - fos gene , were measured . c - fos is a marker of neuronal activation and is correlated with an increase in functional and metabolic activity in the brain , involved in the phenomena of neuronal plasticity , expressed in response to a wide range of stimuli , and implicated in processes such as gene transcription , apoptosis , or proliferation . the main results of the study by quilez and colleagues can be summarized as follows : ( a ) independently of higher or lower vt , mechanical ventilation ' per se ' ( compared with spontaneous breathing ) induced neutrophil infiltration , increased lung damage , and was associated with a greater release of inflammatory markers in both the lung and plasma as well as c - fos activation in central amygdala , hippocampus , paraventricular hypothalamic nuclei , and supraoptic nucleus ; and ( b ) higher vt increased c - fos in the retrosplenial cortex and hypotalamus and increased tumor necrosis factor - alpha in the plasma . therefore , mechanical ventilation promoted brain activation and the intensity of the response was increased with higher vt , suggesting a cross - talk between the brain and lungs . different mechanisms may explain the possible negative effects of mechanical ventilation on the specific anatomical areas of the brain , even in the absence of previous lung disease : ( a ) release of local pulmonary inflammatory mediators in the bloodstream with activation of brain response and ( b ) altered regional cerebral perfusion due to increased mean airway pressure , reduced lymphatic drainage , and activation of the autonomic system ( figure 1 ) . brain injury - associated pulmonary dysfunction has long been attributed only to a greatly increased sympathetic activity with pulmonary venoconstriction and higher capillary permeability , but a recent study reported the role of systemic inflammatory response with pulmonary infiltration of neutrophils , cytokine release , and endothelial dysfunction triggered by an initial sympathetic discharge . a clinical study has shown that , after severe brain injury , higher vt was associated with increased risk of acute lung injury ( ali ) . on the other hand , ali itself induces a systemic inflammatory response with elevated cytokines and neutrophils as well as a dysfunction of other organs , including the brain . protective ventilation could be associated not only with less vali but also with better cerebral oxygenation and perfusion . heuer and colleagues   found that acute intracranial hypertension increased extravascular lung water and increased the amount of poorly aerated tissue in previously healthy lungs without alterations in gas exchange . in experimental ali , intracranial hypertension worsened pre - existing lung damage and further increased brain edema . conversely , ali alone increased the circulating concentrations of the neuronal damage markers ( neuronal serum enolase and s100b ) , but the most severe hippocampal damage was seen in animals with combined ali and intracranial hypertension . this is in agreement with clinical reports   and could indicate a reciprocal , synergistic effect of the two conditions . the study by quilez and colleagues , despite generating interesting data for the near future , has some limitations . first , small animals were used and thus similar results may not be obtained in larger animals with ali . second , rats were ventilated with very high vt ( 30 ml / kg , which is equivalent to 2,100 ml in average - sized adult humans ) . third , protective mechanical ventilation was not applied since no positive end - expiratory pressure ( peep ) was used . therefore , the increase in brain damage and inflammation , even with lower vt , could have been avoided by using moderate peep levels . fourth , moderate hypercapnia and low pha in the low vt group may have affected the results . also , the duration of the experiment was quite short ( 3 hours ) , so that different effects might be observed with longer periods of mechanical ventilation . lastly , the type of sedation during spontaneous breathing and paralyzing agents during mechanical ventilation may affect lung inflammation . in conclusion , recent data from experimental and clinical studies have shown ( a ) increased evidence of a cross - talk between the brain and lungs and ( b ) a reduction in vali as well as brain injury when protective ventilation is adopted . thus , early detection of vali , through clinical signs and measurements of extravascular lung water and of brain injury by measuring specific markers , could help to optimize ventilatory settings and even the overall clinical management of critically ill patients . ali : acute lung injury ; peep : positive end - expiratory pressure ; vali : ventilator - associated lung injury ; vt : tidal volume . this commentary received financial support from the centers of excellence program ( pronex - faperj ) , the brazilian council for scientific and technological development ( cnpq ) , the carlos chagas filho rio de janeiro state research supporting foundation ( faperj ) , and coordination for the improvement of higher level personnel ( capes ) .
brain or lung injury or both are frequent causes of admission to intensive care units and are associated with high morbidity and mortality rates . 
 mechanical ventilation , which is commonly used in the management of these critically ill patients , can induce an inflammatory response , which may be involved in distal organ failure . 
 thus , there may be a complex crosstalk between the lungs and other organs , including the brain . 
 interestingly , survivors from acute lung injury / acute respiratory distress syndrome frequently have some cognitive deterioration at hospital discharge . 
 such neurologic dysfunction might be a secondary marker of injury and the neuroanatomical substrate for downstream impairment of other organs . 
 brainlung interactions have received little attention in the literature , but recent evidence suggests that both the lungs and brain can promote inflammation through common mediators . 
 the present commentary discusses the main physiological issues related to brain - lung interactions .