Search Results (74)

MicroRNA (miRNA), as a key post-transcriptional regulatory factor, plays a crucial role in embryonic development. The coordination of endoderm cell convergence and cardiac precursor cell (CPC) migration is critical for cardiac tube fusion. Defects in endoderm can impair the normal migration of CPCs towards the midline, leading to cardia bifida. Although the role of the microRNA-183 family (miR-183, miR-96 and miR-182) in cardiovascular diseases has been reported, the mechanism by which they regulate early heart development remains unclear. In this study, we used zebrafish as a model to elucidate the roles of the microRNA-183 family in early heart development. miRNA mimics were injected into Tg (cmlc2: eGFP) and Tg (sox17: eGFP) transgenic embryos to overexpress the miR-183 family. The results showed that, at 36 hpf, single or co-injection of miR-183/96/182 mimics caused defects in endoderm convergence, with a hole in the endoderm, and a significant down-regulation of the endoderm marker gene sox32. Additionally, embryos with single or co-injection of miR-183/96/182 mimics exhibited cardia bifida and tail blisters, with significantly down-regulated expression levels of genes related to heart development, including cmlc2, vmhc, amhc, nppa, gata4, gata5, nkx2.5, bmp2b, and bmp4. The phenotype caused by overexpression of the miR-183 family is highly consistent with loss of the sphingosine 1-phosphate receptor S1Pr2. Bioinformatics analysis result found that miR-183 can bind to 3′-UTR of the s1pr2 to regulate its expression; overexpression of miR-183 led to a significant decrease in the expression of the s1pr2 gene. Dual luciferase assay results suggest that s1pr2 is a bona fide target of miR-183. In summary, the miR-183 family regulates endoderm convergence and cardiac precursor cell migration via the S1Pr2 signaling pathway. This study reveals that the miR-183 family is a key regulatory factor in endoderm convergence and cardiac precursor cell migration during the early zebrafish development, elucidating the molecular mechanisms underlying early cardiac precursor cell and endoderm cell movement. Full article

Glottic insufficiency, often caused by laryngeal nerve injury, impairs voice quality and breathing. Current treatments, such as hyaluronic acid injection, require frequent reapplication every 3–6 months. This study aimed to investigate the therapeutic potential of small extracellular vesicles (sEVs) derived from Wharton’s Jelly mesenchymal stem cells (WJMSCs) incorporated into genipin-crosslinked gelatin hydrogels (GCGHs) for promoting vocal fold fibroblast (VFFs) regeneration in vitro. WJMSCs were isolated from umbilical cords, expanded to passage 4, and used for sEV isolation via tangential flow filtration (TFF). The sEVs (585.89 ± 298.93 µg/mL) were characterized using bicinchoninic acid assay (BCA), nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blot. Seven concentrations of sEVs were tested on VFFs to evaluate cytotoxicity and proliferation, identifying 75 µg/mL as the optimal dose. GCGHs were then combined with WJMSCs and sEVs and evaluated for physicochemical properties, degradation, biocompatibility, and immune response. The hydrogels were injectable within 20 min and degraded in approximately 42 ± 0.72 days. The optimal sEV concentration significantly enhanced VFFs proliferation (166.59% ± 28.11) and cell viability (86.16% ± 8.55, p < 0.05). GCGH-MSCs showed the highest VFFs viability (82.04% ± 10.51) and matrix contraction (85.98% ± 1.25) compared to other groups. All hydrogel variants demonstrated minimal immune response when co-cultured with peripheral blood mononuclear cells (PBMCs). GCGH is a promising scaffold for delivering WJMSCs and sEVs to support VFF regeneration, with demonstrated biocompatibility and regenerative potential. Further in vivo studies are warranted to validate these findings. Full article

The chemotherapeutic combination of bleomycin, etoposide, and cisplatin (BEP) is well-documented to exert gonadotoxic effects, ultimately leading to impaired fertility. This experimental rat study investigated the potential protective role of repeated medical ozone therapy in mitigating the deleterious effects of BEP treatment in male rats. Thirty-two adult male Sprague Dawley rats were randomly assigned to four groups: (i) a healthy control group, (ii) a group receiving injections of the BEP regimen over nine weeks, (iii) a group receiving the same BEP regimen plus medical ozone (1 mg/kg IP) twice weekly, and (iv) a group receiving only ozone therapy. BEP treatment significantly reduced sperm concentration and increased morphological abnormalities, both of which were partially restored by ozone co-administration. Ozone therapy also elevated testosterone and thyroid-stimulating hormone (TSH) levels when co-administered with BEP compared to BEP treatment alone. Oxidative stress analysis demonstrated that total oxidative status (TOS) and total antioxidant status (TAS) levels were significantly improved in the BEP + ozone group. Histopathological analysis revealed that ozone treatment ameliorated BEP-induced testicular damage, as evidenced by improved Johnsen scores and increased thickness of the seminiferous tubule epithelium. In conclusion, repeated medical ozone therapy appears to mitigate BEP-induced reproductive toxicity by preserving sperm quality, endocrine function, and redox homeostasis. Full article

Xylazine abuse is emerging as a global problem, whereas the toxic mechanisms of xylazine poisoning are seldom studied. The present study aims to assess the heart injury in xylazine poisoning and uncover the underlying mechanism. Forty male SD rats were randomly dived into four groups: control (saline), low dose (10 mg/kg xylazine), median dose (20 mg/kg xylazine) and high dose (40 mg/kg xylazine). The rats were injected with the drug intraperitoneally for 28 consecutive days, and then cardiac ultrasound examination was performed and serum and heart tissues were collected. Genomic, proteomic, and metabolic omics analyses were conducted. ELISA, RNA sequencing, histopathology examination, RT-qPCR, and Western blot were performed. Repeated injection of xylazine led to a decrease in the expression of cardiac output (CO), ventricular systole (VS), and ventricular diastole (VD), while concurrently elevating the levels of lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin T (c-TNT) in the serum. HE staining analysis showed evidence of contraction band necrosis, interstitial fibrosis, and infiltration by inflammatory cells in animals with xylazine poisoning. The modified genes, proteins, and metabolites were gathered, and the integration of transcriptomic, proteomic, and metabolic networks identified 25 overlapping pathways between the differentially expressed genes and metabolites (DEGs-DEMs) and the differentially expressed proteins and metabolites (DEPs-DEMs) joint pathways. The majority of these pathways pertained to the metabolism of sugars, amino acids, and fats. The proteins associated with fructose and mannose metabolism, as well as cholesterol metabolism, were validated, thereby substantiating their pivotal role in the development of xylazine-induced cardiac injury. Repeated injection of xylazine impaired heart function and the metabolism of fructose and mannose. Cholesterol metabolism pathways were critical in the process of xylazine-induced heart injury. Full article

Background/Objectives: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, poses a significant global health concern. Primarily affecting regions in the northern hemisphere, such as northwest China, which are vital for animal husbandry, it often results in severe hepatic impairment in the host. However, there remains a dearth of knowledge concerning changes in gene expression profiles during the progression of AE. In this study, we employed transcriptome sequencing (RNA sequencing, RNA-Seq) to detect alterations in gene expression profiles in the liver tissues of mice with AE. Our aims were to understand the transcriptome differences in the liver during E. multilocularis infection and to explore the molecular mechanisms underlying the early progression of this disease. Methods: We established a mouse model of AE by intraperitoneally injecting protoscoleces of E. multilocularis. All the inoculated mice were randomly divided into four groups. Liver tissues were collected at 6, 12, 19, and 25 weeks after inoculation. Paired non-infected mouse-derived liver tissues were used as controls, and transcriptome sequencing was carried out. Results: A total of 629 differentially expressed genes (DEGs) were identified. Among them, 370 genes were upregulated and 259 genes were downregulated. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were significantly associated with immune system modulation, the cell cycle, and the fibrosis process during the pathological changes. Additionally, weighted gene co-expression network analysis (WGCNA) identified several genes, including CCNA2, BIRC5, KIF2C, OTC, TLR2, and NCKAP1L. These hub genes involved in immunoinflammatory processes may be related to E. multilocularis larvae infection. Conclusions: The findings of this research provide a theoretical foundation for a more in-depth understanding of the molecular mechanisms of AE. They offer valuable insights into the molecular mechanisms and potential key factors involved in the pathogenesis of this disease. Full article

Dendritic cells (DCs) are major contributors to generating an effective immune response due to their ability to present antigens to T cells. Recently, nanoparticles have been widely used in different medical applications, such as drug-delivery systems, to enhance the function of impaired immune cells. Objectives: This research aims to develop an effective antitumor DC-based vaccine by adsorption of chitosan-nanoparticles (CH-NPs) onto DCs. Methods: Undifferentiated mouse bone marrow progenitor cells were differentiated into mature DCs using cytokines and lipopolysaccharides. CH-NPs were prepared using the ionic gelation method and subsequently used to coat the stimulated DCs. The MTT assay was employed to assess the cytotoxicity of all formulations. To compare the antitumor effect of CH-NPs, DCs, and DCs-CH-NPs, mice were divided into five groups and injected with the respective vaccine formulations. Following immunization, flow cytometry was used to analyze DC and CD4⁺ T cell activation in blood and spleen tissues. Histological samples from the spleen and lymph nodes were also collected. Results: Our findings show that co-stimulatory molecules CD80/CD86 and the DC maturation marker CD83 were upregulated in the vaccinated DCs, indicating their maturation. Moreover, CD83, CD11c, and MHC-II were upregulated in blood and spleen samples in vivo. The DC-CH-NPs vaccinated group had a higher mean percentage of CD83 expression in blood samples (76.7 ± 17.1) compared to the DCs group (47.7 ± 11.0) and the CH-NPs group (37.7 ± 8.6). DC markers, particularly CD83, were highly expressed in spleen samples. Additionally, the DC-CH-NPs vaccinated group had a significantly higher number of CD4⁺ T cells (MFI = 26.1 ± 2.3) compared to the DCs (18.6 ± 1.6) and CH-NPs (13.3 ± 1.4) groups. Conclusions: The present study concludes that the DC-CH-NPs vaccine formulation can induce a potent in vivo immune response. These data may provide valuable insights for developing effective delivery systems for antitumor vaccines. Full article

The aim of our research was to understand the impact of ochratoxin A (OTA) exposure on various physiological and behavioral aspects in adult Wistar rats, and to evaluate the efficacy of a Syzygium aromaticum essential oil (EOC) treatment in restoring the damage caused by this toxin. The essential oils were extracted by hydrodistillation, a yield of 12.70% was obtained for EOC, and the GC-MS characterization of this essential oil revealed that its principal major components are eugenol (80.95%), eugenyl acetate (10.48%), β-caryophyllene (7.21%), and α-humulene (0.87%). Acute OTA intoxication was induced by an intraperitoneal (IP) injection of 289 µg/kg/b.w. every 48 h for 12 doses, resulting in significant reductions in the body and brain weights of exposed rats when compared with controls. The neurobehavioral analysis using several behavioral testing techniques, such as the forced swimming, the dark/light test, the Morris water maze, and the open field test, clearly revealed that OTA exposure causes neurobehavioral disorders, including decreased locomotor activity, a reduced willingness to explore the environment, reflecting a state of stress, anxiety and depression, as well as impaired memory and learning. In addition, OTA intoxication has been associated with metabolic disturbances such as hyperglycemia and hypercortisolemia. However, treatment with EOC mitigated these adverse effects by improving body and brain weights and restoring neurobehavioral function. The in silico analysis revealed significant affinities between clove oils and two tested esterase enzymes (ACh and BuChE) that were more than or similar to the four neurotransmitters “dopamine, serotonin, norepinephrine, and glutamic acid” and the co-crystallized ligands NAG, MES, and GZ5. These results highlight the therapeutic potential of EOC in combating the toxic effects of OTA and pave the way for future research into the mechanisms of action and therapeutic applications of natural compounds in the prevention and treatment of poison-induced diseases. Full article

Modified citrus pectin (MCP) modulates galectin-3, a key player in neuroinflammation linked to Alzheimer’s disease. By inhibiting galectin-3, MCP reduces the brain’s inflammatory response and may alleviate cognitive decline. This study examines MCP’s impact on neuroinflammation, cognitive function, and its role in galectin-3 inhibition in a dementia model. Male Wistar rats were assigned to four groups: control (n = 6), scopolamine (SCP) (n = 7), SCP + MCP (n = 7), and MCP only (n = 7). MCP was administered orally at 100 mg/kg/day via drinking water for six weeks. SCP was injected intraperitoneally at 1 mg/kg for seven days to induce an Alzheimer’s-type dementia model. The researchers assessed cognitive performance through the Morris Water Maze (MWM) test. After behavioral tests, blood and brain tissues, including the hippocampus, were collected and stored at −80 °C for analysis. Immunohistochemistry was used to evaluate superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, brain-derived neurotrophic factor (BDNF), and inflammatory markers (IL-1β, IL-6, TNF-α, and galectin-3). The data were analyzed with SPSS 22. SCP treatment increased lipid peroxidation (MDA) and elevated inflammatory markers (TNF-α, IL-6, and galectin-3), while reducing BDNF and impairing spatial memory. Co-administering MCP with SCP significantly reduced TNF-α, IL-6, and galectin-3 levels; increased BDNF; and improved memory performance. Although MCP did not lower MDA levels, it boosted SOD activity, suggesting antioxidant effects. Modified citrus pectin (MCP) alleviated cognitive impairments and reduced neuroinflammation in Alzheimer’s-type dementia by inhibiting galectin-3. MCP also exhibited antioxidant potential, underscoring its therapeutic promise for neurodegenerative diseases. Full article

Diabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators. In addition to pharmacological interventions for controlling the blood glycaemic level, the main strategies for treating diabetic retinopathy are the intravitreal injections of drugs, surgical treatments, and vitrectomies. The complexity of diabetic retinopathy is due to its close interactions with different cell types (endothelial cells, astrocytes, and Müller cells). The evaluation of the efficacy of novel pharmacological strategies is mainly performed through in vivo models. However, the use of different animal species leads to heterogenic results and ethical concerns. For these reasons, the development of new and reliable in vitro models, such as cell co-cultures and eye organoids, represents an urgent need in this area of research. This review features an overview of the in vitro models used to date and highlights the advances in technology used to study this pathology. Full article

Recent studies have shown that epigallocatechin-3-gallate (EGCG), as an effective antioxidant, could attenuate the oxidative damage, inflammation and necrosis in the liver in response to oxidative stress. The present study investigated whether oral administration of EGCG could effectively alleviate the hepatic histopathological changes and oxidative damage in yellow-feathered broilers induced by tert-butyl hydroperoxide (t-BHP). Broilers were exposed to 600 μmol t-BHP/kg body weight (BW) to induce oxidative stress by intraperitoneal injection every five days, followed by oral administration of different doses of EGCG (0, 20, 40 and 60 mg/kg BW) and 20 mg vitamin E (VE)/kg BW every day during 5–21 days of age. The results showed that t-BHP injection decreased (p < 0.05) body weight and the relative weight of the spleen; the enzyme activities of total antioxidant capacity (T-AOC), catalase (CAT) and total superoxide dismutase (SOD); and gene mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, SOD1, SOD2 and acetyl-CoA carboxylase (ACACA); as well as increased (p < 0.05) necrosis formation, malondialdehyde (MDA) content, reactive oxygen species (ROS)accumulation, and peroxisome proliferator activates receptor-α (PPARα) mRNA expression in the liver of yellow-feathered female broilers at 21 days of age. Treatment with 60 mg EGCG/kg BW orally could enhance antioxidant enzyme activities and reverse the hepatic damage induced by t-BHP injection by reducing the accumulation of ROS and MDA in the liver and activating the Nrf2 and PPARα pathways related to the induction of antioxidant gene expression (p < 0.05). In conclusion, intraperitoneal injection of t-BHP impaired body growth and induced hepatic ROS accumulation, which destroyed the antioxidant system and led to oxidative damage in the liver of yellow-feathered broilers from 5 to 21 days of age. It is suggested that EGCG may play an antioxidant role through the Nrf2 and PPARα signaling pathways to effectively protect against t-BHP-induced hepatic oxidative damage in broilers, and the appropriate dose was 60 mg EGCG/kg BW by oral administration. Full article

CIGB-258 is known to exert anti-inflammatory activity via structural stabilization of apolipoprotein A-I (apoA-I) and functional enhancement of high-density lipoproteins (HDL) against acute toxicity of carboxymethyllysine (CML). The co-presence of CIGB-258 in reconstituted HDL (rHDL) formed larger rHDL particles and enhanced anti-inflammatory activity in a dose-dependent manner of apoA-I:CIGB-258, 1:0, 1:0.1, 1:0.5, and 1:1 of molar ratio, in the synthesis of the rHDL. However, no study has evaluated the enhancement of HDL functionality by the co-presence of lipid-free apoA-I and CIGB-258. The present study was therefore designed to compare the structural stabilization and functional improvement of HDL in the presence of lipid-free apoA-I and CIGB-258 in molar ratios of 1:0, 1:0.1, 1:0.5, and 1:1 within both HDL₂ and HDL₃. As the concentration of CIGB-258 increased, it effectively inhibited the cupric-ion-induced oxidation of HDL, thereby safeguarding apoA-I from proteolytic degradation. Additionally, the wound-healing activity of zebrafish was significantly (p < 0.01) enhanced by the co-addition of apoA-I:CIGB-258 (1:1) up to 1.6-fold higher than apoA-I alone (1:0) under the presence of CML. ApoA-I:CIGB-258 (1:1) treatment exhibited the lowest apoptosis and production of reactive oxygen species against CML-induced damage in the wound site. Also, an increase in wounded tissue granulation and epidermis thickness was observed with increasing concentration of CIGB-258 during 48 h post-treatment via the healing process. Intraperitoneal injection of apoA-I:CIGB-258 mixture remarkably ameliorated the acute paralysis and restored zebrafish swimming ability impaired by the acute toxicity of CML. The increase of CIGB-258 content, especially co-injection of apoA-I:CIGB-258 (1:1), leads to a significant 2.3-fold (p < 0.001) and 4.1-fold (p < 0.001) higher zebrafish survivability and recovery of swimming ability, respectively, than those of CML-control. In the apoA-I:CIGB-258 (1:1) group, neutrophil infiltration and interleukin (IL)-6 production was lowest in the hepatic tissue with the least cellular damage and apoptosis. Additionally, the group treated with apoA-I:CIGB-258 (1:1) demonstrated the lowest plasma levels of total cholesterol (TC) and triglycerides (TG), along with minimal damage to the kidney, ovary, and testicular cells. Conclusively, co-treatment of CIGB-258 with apoA-I effectively mitigated acute inflammation in zebrafish, safeguarded vital organs, structurally stabilized apoA-I, and enhanced HDL functionality. Full article

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus (E. granulosus), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body’s innate immune defenses and compromise the liver’s ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis. Full article

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and is primarily caused by cigarette smoking (CS). Neurocognitive comorbidities such as anxiety and cognitive impairments are common among people with COPD. CS-induced lung inflammation and oxidative stress may “spill-over” into the systemic circulation, driving the onset of these comorbidities. We investigated whether a prophylactic treatment with the NADPH Oxidase 2 (NOX2) inhibitor, apocynin, could prevent CS-induced neurocognitive impairments. Adult male BALB/c mice were exposed to CS (9 cigarettes/day, 5 days/week) or room air (sham) for 8 weeks with co-administration of apocynin (5 mg/kg, intraperitoneal injection once daily) or vehicle (0.01% DMSO in saline). Following 7 weeks of CS exposure, mice underwent behavioral testing to assess recognition and spatial memory (novel object recognition and Y maze, respectively) and anxiety-like behaviors (open field and elevated plus maze). Mice were then euthanized, and blood, lungs, and brains were collected. Apocynin partially improved CS-induced lung neutrophilia and reversed systemic inflammation (C-reactive protein) and oxidative stress (malondialdehyde). Apocynin exerted an anxiolytic effect in CS-exposed mice, which was associated with restored microglial profiles within the amygdala and hippocampus. Thus, targeting oxidative stress using apocynin can alleviate anxiety-like behaviors and could represent a novel strategy for managing COPD-related anxiety disorders. Full article

Memory is one of the most important abilities of our brain. The process of memory and learning is necessary for the proper existence of humans in the surrounding environment. However, sometimes there are unfavourable changes in the functioning of the brain and memory deficits occur, which may be associated with various diseases. Disturbances in the cholinergic system lead to abnormalities in memory functioning and are an essential part of clinical symptoms of many neurodegenerative diseases. However, their treatment is difficult and still unsatisfactory; thus, it is necessary to search for new drugs and their targets, being an alternative method of mono- or polypharmacotherapy. One of the possible strategies for the modulation of memory-related cognitive disorders is connected with the endocannabinoid system (ECS). The aim of the present study was to determine for the first time the effect of administration of natural cannabinoid compound (cannabidiol, CBD) and rivastigmine alone and in combination on the memory disorders connected with cholinergic dysfunctions in mice, provoked by using an antagonist of muscarinic cholinergic receptor—scopolamine. To assess and understand the memory-related effects in animals, we used the passive avoidance (PA) test, commonly used to examine the different stages of memory. An acute administration of CBD (1 mg/kg) or rivastigmine (0.5 mg/kg) significantly affected changes in scopolamine-induced disturbances in three different memory stages (acquisition, consolidation, and retrieval). Interestingly, co-administration of CBD (1 mg/kg) and rivastigmine (0.5 mg/kg) also attenuated memory impairment provoked by scopolamine (1 mg/kg) injection in the PA test in mice, but at a much greater extent than administered alone. The combination therapy of these two compounds, CBD and rivastigmine, appears to be more beneficial than substances administered alone in reducing scopolamine-induced cognitive impairment. This polytherapy seems to be favourable in the pharmacotherapy of various cognitive disorders, especially those in which cholinergic pathways are implicated. Full article

In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain’s adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO₂ was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO₂ and PvO₂; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO₂ and SvO₂. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO₂ steps, but predominantly by hypoxemia at FiO₂ < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO₂ steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia. Full article