Scientists find why ICU ventilation may cause brain damage
Patients who have been mechanically ventilated in intensive care units have long been known to suffer some form of mental impairment as a result. Now, researchers have uncovered a molecular mechanism that may explain why this happens.
The research, printed within the American Journal of Respiratory system and demanding Care Medicine, was carried out by scientists in the College of Oviedo in The country, St. Michael’s Hospital in Canada, and also the Perelman Med school in the College of Pennsylvania.
The scientists state that no less than 30% of patients in intensive care models (ICU) suffer some type of mental disorder, for example anxiety, depression, and many generally, delirium. They observe that the incidence of delirium in patients who’re robotically aired is about 80%.
They hypothesized that this can be partially a direct result damage within the hippocampus, but exactly how ventilation causes this damage continues to be unclear.
Dopamine a cause of apoptosis
Scientists have found a molecular mechanism that could explain why some patients who’re robotically aired in ICUs suffer mental impairments.
For his or her study, the study team examined the gathered brains of rodents who was simply linked to low or high-pressure ventilation for 1 hour 30 minutes, plus the brains of control rodents who was not on ventilation.
In comparison with the control mice, the mice on ventilation showed evidence of neuronal cell death in the hippocampus as a result of apoptosis – the process of programmed cell death (PCD).
The study team learned that the apoptosis process was brought on by dopamine-caused suppression of Akt – a molecule that always prevents neuronal apoptosis.
They observe that within the aired rodents, Akt suppression was clearly apparent within the hippocampus and it was associated with elevated amounts of dopamine (hyperdopaminergic) on the bottom from the brain. The aired rodents also demonstrated elevated gene expression of tyrosine hydroxylase – an enzyme critical in synthesizing dopamine.
The resulting increase in dopamine, the scientists say, increases the effectiveness of activation from the dopamine receptor within the hippocampus.
To confirm these findings, the researchers injected type 2 dopamine (D2) receptor blockers into the brain ventricles of a group of mice. This significantly reduced ventilation-induced apoptosis in the hippocampus.
Dysbindin-1 ‘protects against apoptosis’
The scientists then looked to evaluate the effects of ventilation and elevated dopamine within the hippocampus on dysbindin-1 – a protein that affects amounts of cell surface D2 receptors, cognition, and potentially, chance of psychosis.
Results demonstrated that rodents who experienced high-pressure ventilation demonstrated elevated gene expression of dysbindin-1C. Afterwards along the way, the aired rodents also demonstrated elevated gene expression in protein amounts of dysbindin-1C.
Dopamine alone demonstrated similar effects on dysbindin-1C when examining hippocampus slice formulations, the scientists say, which effects were inhibited by D2 receptors.
The researchers say that since dysbindin-1 is able to reduce cell-surface D2 receptors, as well as protect against apoptosis, it is possible that increasing dysbindin-1 expression in ventilated mice could trigger “compensatory responses” to ventilation-induced hippocampal apoptosis.
They observe that this might potentially affect ICU patients, considering that yet another study finding demonstrated that total dysbindin-1 was elevated within the hippocampal neurons of aired humans who died, although not in non-aired humans.
Potential for new and improved drugs
The scientists say these bits of information can lead to new ways to use old drugs, in addition to potential growth and development of new drugs that can trigger certain molecular pathways in a position to resolve negative effects on thinking processes because of ICU ventilation.
Dr. Konrad Talbot, assistant research professor in Neurobiology within the Department of Psychiatry at Penn Medicine, states:
“The study indicates the need to reevaluate use of D2 receptor antagonists in minimizing the negative cognitive effects of mechanical ventilation in ICU patients and to evaluate the novel possibility that elevation in dysbindin-1C expression can also reduce those effects.”