Mapping the Neuroprotective Landscape of Perioperative Magnesium Sulphate: A Translational Scoping Review

Background/Objectives: Perioperative brain injury arises from interacting pathways including excitotoxicity, neuroinflammation, and endothelial dysfunction, with limited effective pharmacological neuroprotection. Magnesium sulphate has multimodal biological effects that may address these pathways, but its translational role remains unclear. We aimed to map the translational evidence landscape of perioperative magnesium sulphate and evaluate its translational evidence profile across mechanistic, indirect, and direct clinical domains with respect to potential neuroprotective signalling. Methods: A scoping review was conducted following PRISMA ScR. The literature from PubMed, Scopus, the Cochrane Library, and ProQuest was screened using a Population-Concept-Context framework. Eligible studies included randomised trials, observational studies, and evidence syntheses evaluating perioperative magnesium sulphate. Evidence was categorised into direct neurological outcomes, indirect clinical outcomes, biomarker evidence, and mechanistic domains. Results: Eighteen studies were included, comprising randomised trials, observational studies, and reviews. Magnesium was consistently associated with reductions in postoperative pain and opioid consumption and improvements in recovery characteristics and shivering prevention. In contrast, direct neuroprotective outcomes such as cognitive function, cerebral oxygenation, and neurovascular events showed limited and heterogeneous evidence. Mechanistic mapping suggested effects on NMDA receptor modulation, calcium regulation, sympathetic tone, and endothelial stability. Conclusions: Perioperative magnesium sulphate demonstrates consistent indirect benefits related to analgesia and recovery but lacks robust evidence for direct neuroprotection. Its role is best conceptualised as a multimodal modulator of perioperative neural stress rather than a definitive neuroprotective agent. Future studies should adopt multidomain outcome frameworks integrating mechanistic and clinical endpoints to better define its translational impact.