Project Objectives
- Compare hypothermia and isoflurane as anesthesia methods in neonatal mice.
- Determine whether hypothermia produces true anesthesia or immobilisation.
- Identify neural correlates of stress, pain, or hypoxia.
- Assess recovery time and temperature dynamics.
- Produce objective evidence to promote more humane neonatal anesthesia.
- Develop a best‑practice protocol or STAR‑style guideline.
How This Advances 3Rs Implementation
- Introduces the first neural comparison of anesthesia methods in neonatal mice.
- Replaces subjective welfare scoring with objective fMRI and molecular analysis.
- Guides researchers and regulators toward welfare‑optimised methods.
- Reduces repeated studies caused by the unintended effects of sub-optimal anesthesia.
- Lays groundwork for expanded refinement (e.g., physiological monitoring).
Background
Neonatal mice are widely used in research, yet no consensus exists on the most humane anesthesia method for this age group. Researchers traditionally rely on hypothermia, but it remains unclear whether it provides true anesthesia or simply immobilises the animal, and whether pain occurs during rewarming. Isoflurane (a volatile inhalation anesthetic) is increasingly preferred in Europe, but it may induce hypoglycemia and neuroapoptosis, raising its own welfare concerns. Current assessments rely mainly on behavioral observations and limited physiological parameters, which cannot reliably capture pain, stress, or neurological disturbance in neonates.
This uncertainty creates a critical knowledge gap for both animal welfare and scientific quality. The project addresses this by using functional MRI to monitor brain activity during anesthesia and recovery, alongside the use of several molecular markers of relevance, to detect neural activation and injury. It ultimately aims to identify the best method to reduce pain and neurological stress in neonates during anesthesia, to help refine experiments and improve well-being.
