Esketamine, a drug that blocks NMDA receptors, improved neurological function and promoted nerve repair in mice with intracerebral hemorrhage. RNA sequencing and network pharmacology identified neurotrophin-3 and the PI3K/AKT signaling pathway as key targets. Experiments confirmed that esketamine increased NTF3 protein levels, and blocking the PI3K/AKT pathway with a specific inhibitor reduced the drug's therapeutic effects. The findings suggest esketamine activates the NTF3/PI3K/AKT pathway to aid recovery after brain hemorrhage.
Perioperative use of (es)ketamine significantly reduces the risk of postoperative delirium (POD) but does not prevent postoperative neurocognitive disorder (POND). Subgroup analyses indicate that esketamine is more effective for delirium prevention, whereas racemic ketamine provides better cognitive protection.