The impact of a women-led community center on social cohesion in Tripoli, North Lebanon: A pilot randomized controlled trial.

Sepsis is a disease characterized by a systemic inflammatory response triggered by infection, leading to dysregulation of the body's immune system. It can cause multisystemic damage affecting the respiratory, cardiovascular, and nervous systems. About 11 million people worldwide die annually from sepsis‐related infections, making it a major public health crisis threatening lives and health (Goh et al. ). The central nervous system is particularly vulnerable to sepsis‐induced inflammation (Mazeraud et al. ; Iwashyna et al. ; Annane and Sharshar ; Basu et al. ). The mechanisms underlying these adverse neurological effects may involve neuroinflammation, disruption of the blood–brain barrier (BBB), glial cell activation, neuronal injury, and synaptic dysfunction. Crucially, the primary drivers of sepsis‐associated encephalopathy development are imbalances in the brain microenvironment and neuropathology, in which uncontrolled inflammatory responses and immune dysregulation play pivotal roles. Neuroinflammation is an important pathogenic mechanism in psychiatric and neurodegenerative diseases, typically involving glial cell activation and the release of inflammatory mediators (Ding et al. ). During sepsis, inflammatory signals from the periphery can cross the BBB to reach multiple brain regions, including the hippocampus and cortex. Lipopolysaccharide (LPS) is a potent Toll‐like receptor 4 (TLR4) agonist, known to mimic pathogenic stimuli in inflammation and post‐inflammatory cognitive impairment (Lin et al. ). Peripheral LPS administration triggers activation of microglia and astrocytes, increased endoplasmic reticulum stress in the brain, and release of NF‐κB‐mediated cytokines (Yi et al. ; Tang et al. ), processes reflecting key features of neuroinflammation in neuropsychiatric disorders. Specifically, there are structural and functional alterations in the BBB as early as 4 hours after systemic inflammation, allowing peripheral immune cells and inflammatory factors to enter the central nervous system through the damaged BBB. These infiltrated cytokines can directly exert neurotoxicity and activate glial cells (Andonegui et al. ; Xiao et al. ). Overactivated microglia can release large amounts of reactive oxygen species and pro‐inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1) (Yan et al. ); activated astrocytes can produce excessive chemokine ligands (CXCL) and chemokines (CCL), and CCL11 secreted by astrocytes can further activate microglia, increasing the release of inflammatory factors (Farina et al. ). An increasing number of studies indicate that cytotoxic products and released inflammatory mediators induced by neuroinflammation can impair neuronal function and disrupt synaptic plasticity by altering synaptic proteins (Rao et al. ; Lima Giacobbo et al. ). SNAP‐25 (synaptosomal‐associated protein of 25 kDa), SYT1 (synaptotagmin‐1), postsynaptic density protein (PSD‐95), and synaptophysin (SYN) are common proteins which reflect synapse‐related functions. SNAP‐25, SYT1, and SYN are located on the presynaptic membrane, while PSD‐95 is located on the postsynaptic membrane. SNAP‐25 is a membrane‐associated protein belonging to the SNARE complex, primarily localized to the presynaptic membrane of neurons. It mediates the fusion of synaptic vesicles with the cell membrane, thereby facilitating neurotransmitter release. In addition to this classical function, SNAP‐25 also plays a role at the postsynaptic site, participating in receptor transport, dendritic spine morphogenesis, and synaptic plasticity (Fernström et al. ). Research indicates that SNAP‐25 maintains normal NMDAR levels, ensuring the normal induction of long‐term potentiation (LTP). When SNAP‐25 is knocked down in CA1 pyramidal cells in acute slices, the number of NMDARs (GluN1 subunit) on the dendritic surface is decreased to half, leading to impaired LTP (Jurado et al. ). Syt1 is a synaptic vesicle membrane–integrating protein primarily localized in the cytoplasm, containing C2 domains capable of binding calcium ions and phospholipids. It functions not only as a Ca
sensor but also as a multifunctional protein involved in synaptic vesicle fusion and endocytosis, and in various neurodevelopmental and transmission processes such as axonal growth (Greif et al. ). PSD‐95 and SYN are structural marker proteins for synaptic function and are also key proteins for maintaining LTP. Studies have demonstrated decreased levels of SYN and PSD‐95 proteins in the hippocampus and cerebellum of a valproic acid–induced mouse model of autism‐like behavior (Ling et al. ), and similarly reduced synaptic protein levels of SYN and PSD‐95 in mouse models of cognitive decline such as Alzheimer's disease (Ali et al. ). This evidence indicates that synaptic structure and function play crucial roles in cognitive function, depression, and anxiety. Furthermore, studies demonstrate that LPS exposure reduces PSD‐95 and