Nine weeks after neonatal mice were exposed to 10% oxygen and sevoflurane anesthesia (HI-Protect), different neurocognitive behavioral tests were better compared with mice that breathed only breathed 10% oxygen (HI).  (Image source: Thinkstock)
Nine weeks after neonatal mice were exposed to 10% oxygen and sevoflurane anesthesia (HI-Protect), different neurocognitive behavioral tests were better compared with mice that breathed only breathed 10% oxygen (HI). (Image source: Thinkstock)

An intense area of anesthesia research today is whether general anesthetics are potentially harmful to the developing brain. Despite the intense focus on the risk of anesthetics, it is likely that hypoxia poses a much greater risk. We don’t yet know if there is a risk in children from exposure to anesthetics at a young age, but the risks of hypoxic injury are very real. Hypoxia is the primary cause of neurologic injury in children.

In this month’s issue of Anesthesia & Analgesia, Dr. Andreas W. Loepke, Department of Anesthesiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, and colleagues describe possible benefits of anesthetic administration to the immature brain that is exposed to a hypoxic-ischemic insult in the article titled “A Combination of Mild Hypothermia and Sevoflurane Affords Long-Term Protection in a Modified Neonatal Mouse Model of Cerebral Hypoxia-Ischemia.”

Although episodes of ischemia can happen without prior warning, when they can be anticipated, such as during neurosurgery or cardiac surgery, protective strategies can be employed. The Rice-Vanucci neonatal brain ischemia model (RVM) is a mouse model of hypoxic-ischemic insult where mice undergo unilateral carotid ligation and subsequent exposure to systemic hypoxia while breathing spontaneously. In the RVM of developmental brain ischemia, volatile anesthetics have been administered before ischemia and demonstrated weak protection, but they have not been tested during cerebral ischemia. Here, sevoflurane and mild hypothermia as a protective approach for neonatal mice during hypoxic-ischemic episodes was studied.

At 10 days of age, the right common carotid artery was ligated for all mice. After 2 hours of recovery, the mice were then divided into 3 groups: spontaneous respiration breathing 10% oxygen for 60 min (HI); mild hypothermia and controlled ventilation with sevoflurane 3.5% (0.8 MAC) in 10% oxygen for 60 min (HI-Protect); or spontaneously breathing room air for 60 min (Room Air). Survival in the first 24 hours after the experiment was greater in the HI-Protect group compared with the HI group. One week after the ischemic insult, brain weight ratios and injury scores in several regions of the brain were worse in the HI group compared with the HI-Protect group. Nine weeks later, different neurocognitive behavioral tests were better in mice in the HI-Protect group compared with mice that only breathed 10% oxygen in the HI group. Results of the apomorphine challenge, which can assess basal ganglia integrity in adult mice, demonstrated better outcome in the HI-Protect group compared to the HI group. This suggests sustained striatal injury in animals exposed to hypoxic-ischemia at a young age.

These results are important.   Unlike most other similar studies, the monitoring of the animals during anesthesia included measures of arterial blood pressure, heart rate, and cerebral tissue oxygenation. The only criticism is that the authors did not assess the effect of sevoflurane and hypothermia alone.

In the accompanying editorial titled “Pushing the standards forward: in-depth monitoring of physiological parameters in anesthetized neonatal mice,” Dr. Laszlo Vutskits, Department of Anesthesiology, Pharmacology And Surgical Intensive Care, University Hospitals of Geneva, Geneva, Switzerland, and Dr. Piyush Patel, Department of Anesthesiology, University of California San Diego School of Medicine, San Diego, California, note that, “The experiments presented by Lin et al. provide an outstanding example of high quality physiological monitoring and data reporting in newborn animals. They clearly push the standards of rodent preclinical neonatal anesthesia models forward and are important steps in our never-ending effort to improve the translational value of animal models. This is particularly important in a socio-economic context where the benefit of preclinical animal experimentation in biomedical research is continuously questioned.”