Modulating NLRP3 Inflammasome Activity and Enhancing Cortical Synaptic Plasticity: Nanoparticulate Hydrogen's Role in...

Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder closely related to stress and traumatic events. Neuroinflammation and synaptic plasticity may play a role in the neurophysiological mechanisms of anxiety-like behaviors in PTSD. In this study, a novel magnesium hydrosilicide nanosheet (MSN) with anti-inflammatory and antioxidant properties was developed as a potential intervention for behavioral disorders associated with PTSD. Sustained hydrogen release was achieved through an optimized dosing regimen in a rat model subjected to single prolonged stress and electric foot shock (SPS&S), a validated paradigm for PTSD induction. Experimental results showed that a 7-day MSN intervention significantly attenuated anxiety-like behaviors while reversing the synaptic deficits induced by SPS&S in prefrontal cortical regions. Molecular analyses showed a concomitant downregulation of NOD-like receptor protein 3 (NLRP3) inflammasome components (protein as well as RNA levels) and restoration of neuroplasticity markers including brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) protein levels. The therapeutic outcome correlated with the dual ability of hydrogen to inhibit pro-inflammatory signaling cascades and protect synaptic structures. These findings suggest that MSN-mediated hydrogen delivery is an effective strategy to address PTSD-associated affective dysfunction by orchestrating neuroimmune responses and synaptic homeostasis.