Ketone Bodies in Ischemic Stroke: A Review of Neuroprotective Mechanisms and Therapeutic Implications.

Abstract

Ischemic stroke disrupts cerebral metabolism and initiates a cascade of pathological events, including excitotoxicity, mitochondrial dysfunction, and neuroinflammation. These interconnected processes drive neuronal apoptosis, necrosis, and synaptic loss, ultimately leading to irreversible brain injury, persistent neurological deficits, and high rates of long-term disability and mortality. Ketone bodies, including β-hydroxybutyrate, acetoacetate, and acetone, have demonstrated neuroprotective properties through multiple mechanisms. These include sustaining cerebral energy supply and mitochondrial stability, attenuating excitotoxicity and calcium overload, suppressing inflammatory responses, and promoting neural remodeling and functional recovery. Accordingly, ketone bodies are increasingly recognized as a promising therapeutic strategy for ischemic stroke. However, evidence supporting their clinical application and systematic implementation in humans remains limited. In this review we summarize ketone body metabolism and the mechanisms underlying its neuroprotective effects, evaluate the evidence supporting translation from preclinical studies to clinical application, and highlight key challenges that must be addressed in future investigations. Based on the current evidence, we also propose priorities for short-term clinical research and outline future perspectives.