In the present study, we are focused on the integration effects of perioperative risk factors such as surgical insults, traumatic injuries, anesthesia, or hypoxia and demonstrated that the immunometabolite S-2-hydroxyglutarate exacerbated perioperative ischemic brain injury and post-stroke cognitive dysfunction with structural and functional brain changes by enhancing CD8+ T lymphocyte-mediated neurotoxicity. The gene discussed is CD8A; the disease is brain injury.