Instead of hypothermia
The slowing down of metabolism caused by the activation of Q-neurons protected the organs of mice from lack of oxygen
Alina Suleymanova, PCR.news
Some surgical operations on the cardiovascular system involve a temporary stop of blood flow. Such operations are usually preceded by cooling of the body (hypothermia) in order to slow down metabolism (hypometabolism) and preserve organs in hypoxia. However, such measures may be accompanied by a complication, for example, in the form of acute kidney injury.
Researchers from Kyoto University and the Institute of Physico-Chemical Research (Japan) induced a state of hypometabolism in mice without cooling by activating special Q neurons of the hypothalamus containing QRFP (pyroglutamylated RFamide peptide). In earlier studies, it was shown that stimulation of these neurons led to a decrease in body temperature, motor activity and oxygen consumption in mice, that is, the animal passed into a state similar to hibernation (hibernation).
The scientists used transgenic mice whose Q neurons expressed iCre recombinase and divided them into experimental and control groups. An adenoassociated vector with a coding sequence of "designer receptors" binding to ligands developed for them was introduced into the hypothalamus of rodents from the first group. The control mice also received an injection of an empty vector — their Q neurons were not activated.
Clozapine N-oxide (CNO) was chosen as the ligand, which was injected into the abdominal cavity of mice before surgery, which led to the activation of Q neurons and the development of hypometabolism in the experimental group. Some rodents of each group had their temperature maintained at a normal level (35 ° C), the rest — at a reduced level (21.5 ° C, hypothermia). After anesthesia, the scientists simulated ischemia in rodents by squeezing the descending part of the aorta for 15 minutes. Upon completion of the operation, kidneys were extracted from the animals for histological analysis, and blood serum was taken to assess markers of kidney damage: lipocalin associated with neutrophil gelatinase (NGAL), and cystatin C.
According to the results of histological analysis, in hypothermia, the preservation of the structure of the kidneys (nephron tubules) was higher than at normal temperatures, regardless of the activation of Q neurons. However, the concentration of biochemical parameters of early renal dysfunction in the blood serum was two times lower in animals with activated Q-neurons than in controls. Moreover, within the experimental group there were no significant differences in these parameters in mice who underwent surgery under hypothermia and at normal temperature. Thus, hypometabolism caused by activation of Q neurons, even at normal temperatures, reduced the risk of kidney damage to the same extent as hypometabolism caused by hypothermia.
According to the authors of the work, the state of hypometabolism induced by stimulation of Q-neurons is a promising approach to protecting organs from hypoxia during operations on the heart and blood vessels without cooling the human body. However, invasive stimulation of neurons can be dangerous for patients undergoing anticoagulant treatment. Therefore, scientists have set a goal to find pharmacological ways to trigger hypometabolism, affecting not the brain, but peripheral tissues. According to one of the authors, activation of Q-neurons triggers a sequence of biological events that allows organs to exist in a hypometabolic state for several days. Researchers want to find out what these events are in order to trigger them in the body pharmacologically, without the need to activate Q neurons.
Article by Kyo et al. Q neurons–induced hypometabolism ameliorates acute kidney injury in a mouse model mimicking cardiovascular surgery requiring circulatory arrest published in the journal JTCVS Open.
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