ORIGINAL RESEARCH published: 21 February 2022 doi: 10.3389/fncel.2022.789796 Edited by: Ulises Gomez-Pinedo, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Spain Reviewed by: Francisco Javier Sancho-Bielsa, University of Castilla-La Mancha, Spain Alejandro A. Canales-Aguirre, CONACYT Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Mexico *Correspondence: Vicente Muedra vicente.muedra@uchceu.es Vicente Hernández-Rabaza vicente.hernandez@uchceu.es Specialty section: This article was submitted to Cellular Neuropathology, a section of the journal Frontiers in Cellular Neuroscience Received: 05 October 2021 Accepted: 07 January 2022 Published: 21 February 2022 Citation: Muedra V, Rodilla V, Llansola M, Agustí A, Pla C, Canto A and Hernández-Rabaza V (2022) Potential Neuroprotective Role of Sugammadex: A Clinical Study on Cognitive Function Assessment in an Enhanced Recovery After Cardiac Surgery Approach and an Experimental Study. Front. Cell. Neurosci. 16:789796. doi: 10.3389/fncel.2022.789796 Potential Neuroprotective Role of Sugammadex: A Clinical Study on Cognitive Function Assessment in an Enhanced Recovery After Cardiac Surgery Approach and an Experimental Study Vicente Muedra 1,2 * , Vicent Rodilla 3 , Marta Llansola 4 , Ana Agustí 5 , Clara Pla 2 , Antolín Canto 6 and Vicente Hernández-Rabaza 6 * 1 Department of Medicine and Surgery, Faculty of Health Sciences, Institute of Biomedical Sciences, CEU Cardenal Herrera University, CEU Universities, Valencia, Spain, 2 Department of Anesthesiology, Intensive Care Unit and Pain Therapy, University La Ribera Hospital, Valencia, Spain, 3 Department of Pharmacy, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera CEU University, CEU Universities, Valencia, Spain, 4 Neurobiology Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain, 5 Nutrition and Health Research Unit, Department of Microbial Ecology, Institute of Agrochemistry and Food Technology, Spanish Council for Scientific Research (IATA-CSIC), Valencia, Spain, 6 Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera CEU University, CEU Universities, Valencia, Spain Background: Postoperative cognitive dysfunction affects the quality of recovery, particularly affecting the elderly, and poses a burden on the health system. We hypothesize that the use of sugammadex (SG) could optimize the quality of postoperative cognitive function and overall recovery through a neuroprotective effect. Methods: A pilot observational study on patients undergoing cardiac surgery with enhanced recovery after cardiac surgery (ERACS) approach, was designed to compare SG-treated (n = 14) vs. neostigmine (NG)-treated (n = 7) patients. The Postoperative Quality Recovery Scale (PQRS) was used at different times to evaluate cognitive function and overall recovery of the patients. An online survey among anesthesiologists on SG use was also performed. Additionally, an animal model study was designed to explore the effects of SG on the hippocampus. Results: Sugammadex (SG) was associated with favorable postoperative recovery in cognitive domains particularly 30 days after surgery in patients undergoing aortic valve replacement by cardiopulmonary bypass and the ERACS approach; however, it failed to demonstrate a short-term decrease in length of intensive care unit (ICU) and hospital stay. The survey information indicated a positive appreciation of SG recovery properties. SG reverts postoperative memory deficit and induces the expression of anti-inflammatory microglial markers. Frontiers in Cellular Neuroscience | www.frontiersin.org 1 February 2022 | Volume 16 | Article 789796