Esketamine given to mice after traumatic brain injury (TBI) improved neurological outcomes, reduced neuronal death, and lessened neuroinflammation. The drug suppressed astrocyte activation, inhibited pro-inflammatory A1 astrocyte differentiation, and promoted protective A2 astrocyte formation. These effects occurred through inhibition of the METTL5/c-Myc/PD-L1 signaling pathway. The findings suggest esketamine has significant anti-inflammatory and neuroprotective properties that could be relevant for treating TBI.
Repeated exposure to nitrous oxide (N2O) produces antidepressant-like effects in mice by activating the neuronal nitric oxide synthase (nNOS)/nitric oxide (NO) pathway in the medial prefrontal cortex (mPFC). This activation increases burst firing activity and BDNF expression in an nNOS-dependent manner. Blocking nNOS in the mPFC prevented these antidepressant-like effects, suggesting that the nNOS/NO pathway is a key mechanism underlying N2O's antidepressant action.