Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric condition triggered by severe trauma, characterised by dysregulated fear circuitry, hippocampal atrophy with impaired neurogene Show more
Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric condition triggered by severe trauma, characterised by dysregulated fear circuitry, hippocampal atrophy with impaired neurogenesis, chronic neuroinflammation, neuroendocrine dysregulation, and disrupted prefrontal-limbic connectivity. Existing treatments are largely symptomatic, failing to address underlying neurobiological deficits. Emerging regenerative approaches using human stem cells, particularly induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs), human embryonic stem cells (hESCs), mesenchymal stem cells (MSCs), and their extracellular vesicles (EVs), offer mechanistic plausibility for neural repair via direct neuronal replacement, paracrine neurotrophic support (e.g., BDNF, GDNF, VEGF), immunomodulation (e.g., shifting microglia to anti-inflammatory phenotypes), and promotion of synaptic plasticity and epigenetic reprogramming. Preclinical evidence remains limited and largely indirect, with sparse PTSD-specific studies (e.g., one report of iPSC-NPC transplantation reducing fear behaviour and enhancing hippocampal BDNF/neuronal density in a rat model) supplemented by convergent data from adjacent CNS injury paradigms. MSC- and iPSC-derived EVs, enriched with regulatory miRNAs (e.g., miR-124, miR-21, miR-146a), emerge as a safer, cell-free alternative with strong immunomodulatory potential and greater translational feasibility. However, reproducibility is constrained by model variability, lack of independent replication, and absence of PTSD-focused clinical trials. Major challenges include tumorigenicity risks (especially for pluripotent-derived cells), immune rejection, epigenetic/genomic instability, manufacturing scalability, stringent regulatory requirements, and elevated ethical thresholds for invasive therapies in a non-lethal psychiatric disorder. This review examines how stem cell actions align with PTSD brain changes, critically assesses the limited evidence, and suggests a careful translational plan. Show less
Fear memory generalization is a fundamental hallmark of post-traumatic stress disorder (PTSD) that enables animals to use past experience to adapt to changing conditions. The infralimbic cortex (IL) i Show more
Fear memory generalization is a fundamental hallmark of post-traumatic stress disorder (PTSD) that enables animals to use past experience to adapt to changing conditions. The infralimbic cortex (IL) is implicated in suppressing generalized fear, but the underlying molecular mechanisms remain unknown. Here, we demonstrate that S-nitrosylation of Dexras1 (SNO-Dexras1) in the IL drives fear generalization. Dexras1 is activated by nitric oxide (NO) donors as well as by N-methyl-D-aspartic acid (NMDA) receptor-stimulated NO synthesis in cortical neurons. It is found that the level of SNO-Dexras1 is significantly increased in the IL of generalized mice and downregulation of SNO-Dexras1 attenuates fear generalization. Mechanistically, inhibition of SNO-Dexras1 increases the expression of phosphorylated extracellular regulated protein kinases (pERK) and brain derived neurotrophic factor (BDNF), implicating synaptic remodeling in the IL. Our study reveals a key role of SNO-Dexras1 in the fear generalization, which may provide a potential therapeutic strategy for PTSD. Show less
Post-traumatic stress disorder (PTSD), in its partial or full forms, is frequently observed in military populations. It is therefore important to predict the risk of PTSD prior to deployment. Since el Show more
Post-traumatic stress disorder (PTSD), in its partial or full forms, is frequently observed in military populations. It is therefore important to predict the risk of PTSD prior to deployment. Since elevated allostatic load markers have been described in PTSD, we investigated whether these alterations pre-exist before PTSD onset. Our objective was to explore the ability of four allostatic load markers (urinary and blood cortisol, BDNF and 8-iso-PGF2α) to predict partial/full PTSD onset after a 6-month deployment. We conducted a prospective study in a French military cohort deployed to Afghanistan. PTSD was assessed before (M After controlling for age, pre-deployment PCLS scores, and the number of missions, we found that elevated M Asymptomatic subjects at risk of partial/full PTSD exhibit a common pattern of hypothalamic-pituitary axis dysregulation, similar to that observed in established PTSD. Show less
Post-traumatic stress disorder (PTSD) is a stressful mental illness that arises after exposure to unforeseen traumatic events. The majority of PTSD cases are often refractory to pharmacological interv Show more
Post-traumatic stress disorder (PTSD) is a stressful mental illness that arises after exposure to unforeseen traumatic events. The majority of PTSD cases are often refractory to pharmacological interventions. Herein, considering the neuroprotective effects of quercetin and chitosan in several brain disorders, we examined the effect of quercetin-loaded chitosan nanoparticles (QCNPs), administered via nose-to-brain delivery, on PTSD-like phenotypes in mice. QCNPs were synthesized using the ethanol injection method. We observed uniform spherical structure and 120-170 nm diameter of nanoparticles in transmission-electron microscopy analysis. The polydispersity index, zeta potential, and entrapment efficiency were 0.36 ± 0.0104, 39.05 mV, and 81.86 ± 1.60 %, respectively. Male C57BL/6 mice subjected to controlled-cortical impact (CCI) surgery followed by single-prolonged stress (SPS) exhibited PTSD-like symptoms, including deficits in sociability, anxiety and cognition. The CCI + SPS-driven neurobehavioral dysfunctions related to sociability index, anxiety-like phenotype, and cognition were evaluated employing social-approach social avoidance (SASA), elevated zero maze (EZM), Y-maze, and novel object recognition task (NORT). Intranasal delivery of QCNPs, at 0.06 mg/kg of body weight for 14 days, ameliorated CCI + SPS-generated PTSD-like behaviors in mice. The depleted levels of postsynaptic-density protein 95 (PSD-95), brain-derived neurotrophic factor (BDNF), and doublecortin in the hippocampus of CCI + SPS-exposed mice were restored following QCNPs treatment. Moreover, QCNPs administration reduced the expression of astrocyte marker glial-fibrillary acidic protein (GFAP), IBA-1, c-Fos, and proinflammatory cytokines (C-reactive protein, IL-6, TNF-α, and IL-1β) in the hippocampus of CCI + SPS group. These results suggest that nose-to-brain delivery of QCNPs reverses CCI + SPS-generated PTSD-like phenotypes by modulating neuroinflammatory mediators and enhancing neuronal and synaptic proteins. Show less