By: 16 April 2019
Anaesthesia sends neurones down the wrong path in unborn rat babies

While there has long been discussion whether exposure to anaesthesia affects brain development, new Rush University Medical Center research published in the journal Cerebral Cortex describes how prenatal anaesthesia in rats seems to disrupt the “precisely choreographed” and timed migration of neurones to the area of the developing brain where thinking, memory and language occur.

The finding further fuels the debate about the safety of the anaesthesia in pregnancy for unborn babies, with researchers suggesting the estimated 75,000 women undergo surgery while pregnant more closely examine surgery timing.

In a series of experiments detailed in the study In utero Exposure to Anesthetics Alters Neuronal Migration Pattern in Developing Cerebral Cortex and Causes Postnatal Behavioral Deficits in Rats, researchers demonstrated how exposing pregnant rats to anaesthetics affects neuronal migration, the process in mammals in which neurones migrate from their original position deep inside the brain to their final position on the outer edge, or cerebral cortex.

“The cerebral cortex, or grey matter, is the brain’s computer processor. Cognitive processes like thinking, memory, and language are directed there, thus neurones never reaching their proper and predetermined positions in the cortex may have a profound impact on brain function” said the study’s lead author, anaesthetist and neuroscientist Vicko Gluncic.

To test that hypothesis, researchers marked migrating neurones in rat feotuses with a dye and then anaesthetised one group of pregnant rats during the precise period when neuronal migration occurs is its most active. That gestation period roughly corresponds to the late second trimester in humans – when motoric areas of the brain are already well developed while somatosensory and visual cortex is still developing. A control group was not anaesthetised. Examinations of the rats exposed to anaesthetics showed that significant number of neurones remained inappropriately scattered in deeper layers of cortex, and the longer the rats were exposed to prenatal anaesthesia, the more scattered their neurones. A second set of behavioural experiments showed that all the littermates had consistent motor skills, but those exposed to anaesthetics had significant behavioural and learning deficits.

Together, the histological analysis of the rat brains and the behavioural testing demonstrates that in utero exposure to anaesthesia negatively impacts formation of the most sensitive part of the brain by impeding neurones migration pattern. And in spite of these potent and potentially disastrous alterations, the authors say that the effects of anaesthetics on neuronal migration and development of cortical columnar organisation have never been tested before.

Mario Moric, a biostatistician in Rush’s Department of Anesthesiology, indicated that “there is a clear association of anaesthesia type and anaesthetic duration with neuronal migration and cognitive deficits at the drug levels used here (in rat feotuses), what is needed now is to further validate the mechanisms involved as well as test various anaesthetics and anaesthetic protocols to evaluate differential impact on cognitive functioning”

Study authors stressed that the finding in rats cannot translate directly to pregnant women cancelling or postponing needing surgery, though suggested the findings should be considered in inform discussions between women and their physicians.

“We don’t want to push the panic button,” Gluncic says. “It would be wrong if women delay or stop having medically indicated surgeries during pregnancy because of this. However, non-urgent surgeries in pregnancy are typically performed in the second trimester, after organogenesis, and when preterm contractions and spontaneous abortion are less likely than in last trimester. Based upon the present data, the possibility that anaesthesia may affect feotal brain development should be seriously considered and disclosed in informed consent for anaesthesia in the second trimester since the most active period of human feotal brain development actually occurs between 12th and 24th week of pregnancy.”

Source: Rush University Medical Centre

Reference: V Gluncic, and others. In utero Exposure to Anesthetics Alters Neuronal Migration Pattern in Developing Cerebral Cortex and Causes Postnatal Behavioral Deficits in RatsCerebral Cortex, 2019; DOI: 10.1093/cercor/bhz065