ICU Ventilation Linked to Brain Damage
Researchers at the University of Oviedo in Spain, St. Michael’s Hospital in Toronto, Canada, and the Perelman School of Medicine at the University Pennsylvania discovered a molecular mechanism that may explain the connection between mechanical ventilation and hippocampal damage in ICU patients. The findings were published in the American Journal of Respiratory and Critical Care Medicine.
What is Hippocampal Damage?
The hippocampus is a brain structure which lies under the medial temporal lobe, one on each side of the brain. The hippocampus is crucial for the formation of new autobiographical and fact memories.
It may function as a memory “gateway” through which new memories must pass before entering permanent storage in the brain. Hippocampal damage can result in anterograde amnesia: loss of ability to form new memories, although older memories may be safe.
Description of the Study
According to Medical News Today, at least 30 percent of patients in intensive care units (ICUs) suffer some form of mental illness as reflected in anxiety, depression, and especially delirium. In mechanically-ventilated ICU patients, the incidence of delirium is particularly high, about 80 percent, and may be due in part to damage in the hippocampus, though how ventilation is increasing the risk of damage and mental impairment has remained ambiguous.
The investigators began by studying the hippocampus in control mice and in mice on low or high-pressure mechanical ventilation for 90 minutes. In comparison to the controls, those on either low- or high-pressure ventilation showed evidence of neuronal cell death in the hippocampus, as a result of a cell suicide program called apoptosis.
Searching tirelessly for the molecular cause of the ventilation-induced apoptosis, the team discovered that a well-known apoptosis trigger had been set off in the hippocampus of the ventilated animals. That trigger is dopamine-induced suppression of a molecule known as Akt.
Results of the Study
The investigators hypothesized that ventilation-induced apoptosis in the hippocampus was at least partially mediated by elevated activation of dopamine receptors in that area of the brain. In these mice, mechanical ventilation had virtually little to no effect on levels of the dopamine-synthesizing enzyme or on apoptosis in the hippocampus.
The findings could eventually lead to new therapeutic uses of established drugs and targets for new drugs that activate a molecular pathway mediating adverse effects of ICU ventilation on brain function.