Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents

SIMPLE SUMMARY: The development of innovative therapeutic strategies involving chronic drug delivery to specific brain regions has been crucial in preclinical neuroscience. However, these strategies involve complex surgeries due to the need for implanting a drug storage system connected to the brain through a cannula while ensuring animal welfare, which is a challenge, especially for long-term studies in rodents. In this study, we propose an optimized method with three main refinements: (i) modifying the dimensions of the implantable devices, (ii) using a combination of adhesive tissue and UV light-curing resin, and (iii) implementing a customized scoresheet to closely monitor animal welfare throughout the experiment. Overall, the proposed refinements significantly improved animal welfare, reduced complications related to surgery, increased animal survival, and ensured safe long-term implantations. ABSTRACT: Stereotaxic surgeries enable precise access to specific brain regions, being of particular interest for chronic intracerebroventricular drug delivery. However, the challenge of long-term studies at this level is to allow the implantation of drug storage devices and their correct intrathecal connection while guaranteeing animal welfare during the entire study period. In this study, we propose an optimized method for safe intrathecal device implantation, focusing on preoperative, intraoperative, and postoperative procedures, following the 3Rs principle and animal welfare regulations. Our optimized protocol introduces three main refinements. Firstly, we modify the dimensions of the implantable devices, notably diminishing the device-to-mouse weight ratio. Secondly, we use a combination of cyanoacrylate tissue adhesive and UV light-curing resin, which decreases surgery time, improves healing, and notably minimizes cannula detachment or adverse effects. Thirdly, we develop a customized welfare assessment scoresheet to accurately monitor animal well-being during long-term implantations. Taken together, these refinements positively impacted animal welfare by minimizing the negative effects on body weight, surgery-related complications, and anxiety-like behaviors. Overall, the proposed refinements have the potential to reduce animal use, enhance experimental data quality, and improve reproducibility. Additionally, these improvements can be extended to other neurosurgical techniques, thereby advancing neuroscience research, and benefiting the scientific community.