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.
In patients with disorders of consciousness, the anesthetic esketamine preserved brain electrical complexity and gamma-band functional connectivity better than propofol during spinal cord stimulator implantation. Esketamine was linked to faster recovery of spontaneous breathing (12 vs. 17 minutes on average) and a lower need for blood pressure support during surgery. At three months, esketamine was associated with significantly improved consciousness outcomes. The findings suggest esketamine may offer neuroprotective benefits in this population.