Search Results (7)

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood–brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge. Full article

The mechanism of long-term cognitive impairment after neonatal sepsis remains poorly understood, although long-lasting neuroinflammation has been considered the primary contributor. Necroptosis is actively involved in the inflammatory process, and in this study, we aimed to determine whether neonatal sepsis-induced long-term cognitive impairment was associated with activation of necroptosis. Rat pups on postnatal day 3 (P3) received intraperitoneal injections of lipopolysaccharide (LPS, 1 mg/kg) to induce neonatal sepsis. Intracerebroventricular injection of IL-1β-siRNA and necrostatin-1 (NEC1) were performed to block the production of IL-1β and activation of necroptosis in the brain, respectively. The Morris water maze task and fear conditioning test were performed on P28–P32 and P34–P35, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-PCR), and Western blotting were used to examine the expression levels of proinflammatory cytokines and necroptosis-associated proteins, such as receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Sustained elevation of IL-1β level was observed in the brain after initial neonatal sepsis, which would last for at least 32 days. Sustained necroptosis activation was also observed in the brain. Knockdown of IL-1β expression in the brain alleviated necroptosis and improved long-term cognitive function. Direct inhibition of necroptosis also improved neurodevelopment and cognitive performance. This research indicated that sustained activation of necroptosis via IL-1β contributed to long-term cognitive dysfunction after neonatal sepsis. Full article

Bacterial sepsis induces the production of excessive pro-inflammatory cytokines and oxidative stress, resulting in tissue injury and hyperinflammation. Patients recovering from sepsis have increased rates of central nervous system (CNS) morbidities, which are linked to long-term cognitive impairment, such as neurodegenerative pathologies. This paper focuses on the tissue injury and hyperinflammation observed in the acute phase of sepsis and on the development of long-term neuroinflammation associated with septicemia. Here we evaluate the effects of Coriolus versicolor administration as a novel approach to treat polymicrobial sepsis. Rats underwent cecal ligation and perforation (CLP), and Coriolus versicolor (200 mg/kg in saline) was administered daily by gavage. Survival was monitored, and tissues from vital organs that easily succumb to infection were harvested after 72 h to evaluate the histological changes. Twenty-eight days after CLP, behavioral analyses were performed, and serum and brain (hippocampus) samples were harvested at four weeks from surgery. Coriolus versicolor increased survival and reduced acute tissue injury. Indeed, it reduced the release of pro-inflammatory cytokines in the bloodstream, leading to a reduced chronic inflammation. In the hippocampus, Coriolus versicolor administration restored tight junction expressions, reduce cytokines accumulation and glia activation. It also reduced toll-like receptor 4 (TLR4) and neuronal nitric oxide synthase (nNOS) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome components expression. Coriolus versicolor showed antioxidant activities, restoring glutathione (GSH) levels and catalase and superoxide dismutase (SOD) activities and reducing lipid peroxidation, nitrite and reactive oxygen species (ROS) levels. Importantly, Coriolus versicolor reduced amyloid precursor protein (APP), phosphorylated-Tau (p-Tau), pathologically phosphorylated tau (PHF1), phosphorylated tau (Ser202 and Thr205) (AT8), interferon-induced transmembrane protein 3 (IFITM3) expression, and β-amyloid accumulation induced by CLP. Indeed, Coriolus versicolor restored synaptic dysfunction and behavioral alterations. This research shows the effects of Coriolus versicolor administration on the long-term development of neuroinflammation and brain dysfunction induced by sepsis. Overall, our results demonstrated that Coriolus versicolor administration was able to counteract the degenerative process triggered by sepsis. Full article

Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associated neurological consequences have a great impact on patients, both in the acute phase and in the long term. Sepsis-associated encephalopathy (SAE) is a severe brain dysfunction that may contribute to long-term cognitive impairment. Its pathophysiology recognizes the following two main mechanisms: neuroinflammation and hemodynamic impairment. Clinical manifestations include different forms of altered mental status, from agitation and restlessness to delirium and deep coma. A definite diagnosis is difficult because of the absence of specific radiological and biological criteria; clinical management is restricted to the treatment of sepsis, focusing on early detection of the infection source, maintenance of hemodynamic homeostasis, and avoidance of metabolic disturbances or neurotoxic drugs. Full article

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis. Full article

Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy. Full article

Sepsis is commonly experienced by infants born very preterm (<32 weeks gestational age and/or <1500 g birthweight), but the long-term functional outcomes are unclear. The objective of this systematic review was to identify observational studies comparing neurodevelopmental outcomes in very preterm infants who had blood culture-proven neonatal sepsis with those without sepsis. Twenty-four studies were identified, of which 19 used prespecified definitions of neurodevelopmental impairment and five reported neurodevelopmental outcomes as continuous variables. Meta-analysis was conducted using 14 studies with defined neurodevelopmental impairment and demonstrated that very preterm infants with neonatal sepsis were at higher risk of impairments, such as cerebral palsy and neurosensory deficits, compared with infants without sepsis (OR 3.18; 95% CI 2.29–4.41). Substantial heterogeneity existed across the studies (I² = 83.1, 95% CI 73–89). The five studies that reported outcomes as continuous variables showed no significant difference in cognitive performance between sepsis and non-sepsis groups. Neonatal sepsis in very preterm infants is associated with increased risk of neurodevelopmental disability. Due to the paucity of longitudinal follow-up data beyond 36 months, the long-term cognitive effect of neonatal sepsis in very preterm infants could not be conclusively determined. Effects on the development of minor impairment could not be assessed, due to the small numbers of infants included in the studies. Full article