RARE DISEASE
Delayed encephalopathy due to carbon monoxide poisoning
Delayed encephalopathy due to carbon monoxide poisoning
Delayed encephalopathy due to carbon monoxide poisoning
Synonyms: Delayed encephalopathy due to CO poisoning
Synonyms: Delayed encephalopathy due to CO poisoning
Synonyms: Delayed encephalopathy due to CO poisoning
Drug discovery
1
drug
With orphan designation
Overview
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) manifests days to weeks post-exposure following a lucid interval. Characterized by cognitive decline, memory loss, motor dysfunction, and psychiatric symptoms, it arises from hypoxic-ischemic injury causing white matter demyelination and basal ganglia lesions [1][5][14]. Prognosis varies: 50% experience long-term sequelae, while fatal outcomes may occur with complications like pneumonia [4][6][9].
Therapies
First-line: Hyperbaric oxygen (HBO) ± adjuncts (dexamethasone, N-butylphthalide) [1][3][13].
Emerging: Mesenchymal stem cell transplantation (superior to HBO in some trials) and combination therapies (e.g., HBO + XingZhi-YiNao granules) [1][3][7].
Experimental: Methylene blue (reduces oxidative stress) and immunomodulators [7][11][13].
Categories: rare disorders due to toxic effects, rare neurological diseases
Research Papers
130 drug discovery papers about Delayed encephalopathy due to carbon monoxide poisoning, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
130 drug discovery papers about Delayed encephalopathy due to carbon monoxide poisoning, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-05-07 | Acupuncture for the treatment of Delayed Encephalopathy after Acute Carbon Monoxide Poisoning: a case report.
Delayed Encephalopathy after Acute Carbon Monoxide Poisoning (DEACMP) is characterized by delayed neuropsychiatric deterioration after a period of apparent recovery. Effective treatments remain limited. A 75-year-old male developed cognitive decline, motor dysfunction, incontinence, and sleep disturbance persisting for more than 3 months after carbon monoxide poisoning despite standard therapy. MRI showed diffuse white matter demyelination. Zhu's scalp acupuncture combined with body acupuncture was administered once daily for 15 sessions. Baseline MMSE and AD8 were not testable due to severe disorganized speech and poor cooperation. After treatment initiation, MMSE improved from 11 (after 1 session) to 14 (after 3 sessions), 24 (after 15 sessions), and 26 at one-month follow-up. AD8 decreased from 7 to 5, 2, and 1 at the corresponding time points. Functional independence was restored. No adverse events were reported. The temporal pattern of improvement suggests a possible association between acupuncture intervention and neurological recovery. Controlled studies are needed to further evaluate efficacy.
2026-04-04 | The role of sGC-cGMP-PKG signaling pathway-mediated excitotoxicity in delayed encephalopathy after carbon monoxide poisoning.
This study investigated the role of soluble guanylate cyclase-cyclic guanosine monophosphate-protein kinase G (sGC-cGMP-PKG) signaling pathway in the regulation of carbon monoxide (CO) on glutamate neurotransmitter system and neuronal excitotoxicity in vitro and in vivo, and revealed the possible mechanism of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). The results showed that compared with the control group, a large number of apoptotic cells appeared in the hippocampus of mice 7 and 14 days after CO exposure, and the learning and spatial memory functions were decreased. The protein expression levels of heme oxygenase-1 (HO-1), sGC, PKG, N-methyl-D-aspartate receptor 2 A (NR2A) and N-methyl-D-aspartate receptor 2B (NR2B) and the concentrations of glutamate, cGMP and calcium ion (Ca²⁺) were significantly increased at different time points after CO exposure. At the same time, in the in vitro model of acute CO poisoning, the expression of HO-1, sGC, PKG, NR2A and NR2B in PC12 cells exposed to different concentrations of CO increased, glutamate release increased, Ca²⁺ overload, excitotoxicity, and then led to cell apoptosis. After treatment with sGC specific inhibitor, the expression level of N-methyl-D-aspartate (NMDA) receptor protein and Ca²⁺ concentration were significantly decreased, the number of apoptotic cells was significantly decreased, and the animal behavior related indicators were improved. The results of the present study suggest that excitotoxicity mediated by sGC-cGMP-PKG signaling plays an important role in DEACMP induced by CO poisoning.
2026-02-23 | Optimizing hyperbaric oxygen initiation time in carbon monoxide poisoning: a 3-hour window enhances neurological recovery via lactate clearance.
To explore the optimal initiation time of hyperbaric oxygen therapy (HBOT) for moderate-to-severe acute carbon monoxide poisoning (ACOP) and to assess the prognostic value of lactate clearance and early MRI findings. This single-center retrospective study included 12 ACOP patients (2020-2023) treated with HBOT within 6 h after admission. Patients were categorized by HBOT initiation time: early (≤3 h, n=8) and delayed (>3 h, n=4). Clinical, biochemical, and imaging data were analyzed. Primary outcomes were time to regain consciousness and Barthel Index at 6 months. Median HBOT initiation was 112 min. Early treatment was associated with faster organ function recovery (greater SOFA score reduction, p<0.05). Lactate normalized within a median of 17.5 h, and clearance >50 % in 24 h correlated with better neurological outcomes (p=0.002). MRI detected early globus pallidus injury more sensitively than CT. At 6 months, 83.3 % recovered functionally; one developed delayed encephalopathy. Early HBOT initiation (≤3 h) may facilitate metabolic and neurological recovery in ACOP. Early lactate clearance and MRI findings may serve as prognostic markers. Given the small sample size and absence of a non-HBOT control group, these results are exploratory and require confirmation in larger studies.
2025-11-30 | High-density lipoprotein cholesterol protects against delayed encephalopathy after acute carbon monoxide poisoning.
High-density lipoprotein cholesterol (HDL-C) plays a crucial role in neurological disorders. In this study, we aimed to elucidate the role of HDL-C in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), which presents with both neurological and psychiatric symptoms. Two-sample Mendelian randomization was employed on 201 lipid summary statistics to investigate potential causality. Data from the FinnGen database of 306,787 individuals were used. Mendelian randomization analysis results were screened using Bayesian model averaging. The results were validated in a multicenter cohort of 1368 patients, and the role of the antioxidant properties of high-density lipoprotein in DEACMP was examined. Mendelian randomization analysis identified six high-density lipoprotein-related variants significantly associated with DEACMP, with the cholesterol to total lipids ratio in medium high-density lipoprotein showing the strongest effect (marginal inclusion probability = 0.51, p = 1.00 × 10-3, false discovery rate = 6.00 × 10-3). Clinical validation confirmed HDL-C as an independent protective factor. Patients without DEACMP had higher high-density lipoprotein oxidant index values (1.23 [interquartile range: 1.02-1.36]) than those who developed DEACMP (0.84 [interquartile range: 0.66-0.90]); the high-density lipoprotein oxidant index declined significantly in postmenopausal women (p = 0.023). These findings demonstrate that HDL-C mitigates the risk of DEACMP through its antioxidant capacity. The integration of genetic evidence, clinical validation, and functional assays provides robust support for HDL-C as a predictive biomarker of neural recovery after carbon monoxide poisoning.
2025-11-09 | Axin-1, modified by IGF2BP2-dependent m6A, triggers neuronal ferroptosis in delayed encephalopathy animal model caused by carbon monoxide poisoning via Smurf1-mediated BDNF ubiquitination.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a common complication after carbon monoxide poisoning. This study focused on the role and mechanism of Axin-1 regulating ferroptosis in DEACMP. Nissl staining, immunohistochemistry, immunofluorescence and Prussian blue were used to evaluate the histopathology and iron distribution of DEACMP rats. The N6-methyladenosine (m6A) level of Axin-1 was analyzed by m6A-RNA immunoprecipitation and qPCR (MeRIP-qPCR). The mRNA and protein levels of the molecules were tested by RT‑qPCR and Western blot. RNA immunoprecipitation (RIP) and Co-immunoprecipitation (Co-IP) experiments were used to verify the interaction between molecules. Cell viability and apoptosis were detected using Cell counting kit-8 (CCK-8) and Terminal deoxynucleotidyl transferase dUTP nick (TUNEL) staining. Reactive oxygen species (ROS) levels were measured by flow cytometry. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), and Fe2+ were evaluated by biochemical kits. The expression of Axin-1 in DEACMP rats was increased, and its up-regulation was related to IGF2BP2-mediated m6A modification. Overexpression of Axin-1 abolished the protective inhibition of IGF2BP2 depletion-mediated oxidative damage and ferroptosis induced by oxygen and glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Axin-1 promoted the ubiquitination and degradation of BDNF by targeting Smurf1. Overexpressed Axin-1 inhibited the protective effect of BDNF on oxidative damage and ferroptosis. The Nrf2/HO-1 pathway played a role in OGD/R-triggered ferroptosis, which was mediated by Axin-1. The IGF2BP2/Axin-1 axis also regulated ferroptosis in vivo. IGF2BP2-mediated m6A modification of Axin-1 promoted oxidative damage and neuronal ferroptosis by modulating Smurf1/BDNF and Nrf2/HO-1 pathways in DEACMP animal model and OGD/R cell model. Therefire, Axin-1 may be a potential therapeutic target for the treatment of DEACMP.
cell therapies
2021-10-21 | BMSC-derived Exosomes Protect Against Delayed Encephalopathy after Acute Carbon Monoxide Poisoning in Rats via Blockade of Notch Signaling
Abstract Objective: Our aim was to probe the therapeutic effect by which (BMSC-ex) protect against (DEACMP) in rat models in vivo. Methods: BMSC-ex were successfully characterized and proven to pass the blood brain barrier and migrate to the injured brain area. Rats were randomly divided into six groups and the cognitive function of mice was evaluated by the morris water maze. The severity of pathological changes was evaluated by HE staining and LFB staining. The expression of cytokines was detected by ELISA. Immunohistochemical staining and western blot analysis were utilized to detect the protein expression of Foxp3、CD4、MBP、Notch1 and Hess1 in brain tissue.Results: We found that BMSC-ex significantly reduced inflammation, increased the levels of (Tregs), relieved demyelination, and ameliorated the cognitive impairment in DEACMP rats. Furthermore, inhibiting the Notch pathway led to a partial reversal of the effect of BMSC-ex in mice.Conclusions: BMSC-ex relieved the severity of demyelination in the DEACMP rat models by regulating Tregs subsets and the expression of Notch signaling. Hence BMSC-ex play a protected role in DEACMP by upregulating Tregs and the regulatory components of Notch signaling and this may provide a new clinical strategy for the treatment of DEACMP patients.
2013-08-01 | Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication
Abstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs) to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI). The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy. Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE
2010-10-26 | Treatment of acute carbon-monoxide poisoning with therapeutic erythrocytapheresis: Clinical effects and results in 17 victims
Seventeen cases of acute carbon-monoxide poisoning were treated with therapeutic red cell-exchange. Glasgow Coma Scale score was used to evaluate the level of consciousness. The mean carboxyhemoglobin level decreased from 0.286 ± 0.1805 (28.6 ± 18.05%) to 0.0613 ± 0.0418 (6.13 ± 4.18%) and Glasgow Coma Scale score increased from 10 ± 3 to 13.76 ± 1.89. While 11 patients scored 15 at the end of the treatment, four scored 15 in an hour after the treatment. None of the patients died. Two victims (11.7%) experienced ischemic encephalopathy. Therapeutic red cell-exchange therapy can be an effective treatment in reducing mortality and morbidity in carbon-monoxide poisoning.
2009-05-05 | Structural and functional improvement of injured brain after severe acute carbon monoxide poisoning by stem cell-based therapy in rats.
We investigated the feasibility and efficacy of bone marrow mesenchymal stem cells (BMSCs)-derived neural stem-like cells (MS-NSCs) therapy on injured brain in rats after severe acute carbon monoxide (CO) poisoning. Controlled animal study. Research laboratory of a university hospital. Sprague-Dawley rats weighing 230 +/- 20 g and 90 +/- 10 g. The rats were exposed to 1000 ppm CO in air for 40 minutes and then to 3000 ppm for another 20 minutes until they lost consciousness. Approximately 7 x 10 allogeneic BMSCs or MS-NSCs labeled with BrdU were infused into the poisoned rats via the internal carotid after a 24-hour resuscitation. The rats with and without CO poisoning were used as placebo and sham controls, respectively. The neurologic and cognitive functions were evaluated by Neurologic Severity Scores and Morris water maze tests. Examinations with immunohistochemistry, myelin, and hematoxylin-eosin staining were made to assess cerebral structure after 5 weeks. Histologically, the compactness and arrangement of the insulted white matter were improved by the cellular treatments. The transplanted MS-NSCs were positive for microtubule-associated protein 2 in hippocampus, 84.6% +/- 5.6%, and for glial fibrillary acidic protein in subventricular white matter and hippocampus, 32.2% +/- 2.5% and 9.7% +/- 1.2%, respectively, although the MS-NSCs group showed a larger fraction in the expression of the above markers in corresponding domains compared with the BMSCs group. The MS-NSCs also displayed a higher survival rate than BMSCs in most domains of diffusively injured brain, leading to a better improvement in the Morris water maze test (p < 0.05). The stem cell-based therapy could be advantageous for improving the structure and function of injured brain in rats after severe acute CO poisoning, indicating the potential use as a novel approach for severely CO-poisoned patients with delayed neurologic sequelae. Furthermore, MS-NSCs may render better therapeutic effects after neurologic injury than untreated BMSCs.
2009-05-01 | HEMOGLOBIN VESICLES AND RED BLOOD CELLS AS CARRIERS OF CARBON MONOXIDE PRIOR TO OXYGEN FOR RESUSCITATION AFTER HEMORRHAGIC SHOCK IN A RAT MODEL
Hemoglobin vesicles (HbVs) are artificial oxygen (O2) carriers that encapsulate concentrated hemoglobin (Hb) solution in phospholipid vesicles (liposomes). Recent reports on cytoprotective effects of exogenous carbon monoxide (CO) urged us to test infusion of CO-bound HbV (CO-HbV) and red blood cells (CO-RBC) in hemorrhagic-shocked rats to improve tissue viability over that of O2-bound HbV (O2-HbV) and O2-bound RBC (O2-RBC). Male Wistar rats were anesthetized with 1.5% sevoflurane inhalation (FiO2 = 21%) while spontaneous breathing was maintained. Shock was induced by 50% blood withdrawal from femoral artery. Fifteen minutes later, they received CO-HbV, CO-RBC, O2-HbV, O2-RBC, or empty vesicles (EV) suspended in 5% recombinant albumin. All groups showed prompt recovery of blood pressure and blood gas parameters just after resuscitation and survived for 6 h of observation period. However, only the EV group showed significant hypotension at 3 and 6 h. Plasma enzyme levels were elevated at 6 h, especially in the O2-HbV, O2-RBC, and EV groups. They were significantly lower in the CO-HbV and CO-RBC groups than in the O2-bound fluids. Immunohistochemical staining of 3-nitrotyrosine exhibited less oxidative damage in the liver and lung for CO-HbV and CO-RBC groups. Blood carbonyl Hb levels (26%-39% immediately after infusion) decreased to less than 3% at 6 h while CO was exhaled through the lung. Both HbV and RBC gradually gained the O2 transport function. Collectively, both CO-HbV and CO-RBC showed a resuscitative effect for hemorrhagic-shocked rats. They reduced oxidative damage to organs in comparison to O2-HbV and O2-RBC. Adverse and poisonous effects of CO gas were not evident for 6 h in this experimental model. Further study is necessary to clarify the neurological impact of a longer observation period for eventual clinical applications. ABBREVIATIONS-Hb-hemoglobin; HbV-Hb vesicles; CO-HbV-CO-bound HbV; RBC-red blood cell; CO-RBC-CO-bound RBC; EV-empty vesicles; HO-heme oxygenase; HBOC-hemoglobin-based oxygen carrier; rHSA-recombinant human serum albumin; Hct-hematocrit; PaO2-arterial blood O2 tension; PaCO2-arterial blood CO2 tension; HR-heart rate; AST-aspartate aminotransferase; ALT-alanine aminotransferase; LDH-lactate dehydrogenase; Mb-myoglobin; NOS-nitric oxide synthase
proteins
2022-04-01 | Effect of Recombinant Human Brain Natriuretic Peptide on Acute Carbon Monoxide Poisoning Complicated with Heart Failure with Reduced Ejection Fraction.
This paper aims to observe the effect of recombinant human brain natriuretic peptide (rhBNP) on treatment of acute carbon monoxide poisoning (ACMP) complicated with heart failure with reduced ejection fraction (HFREF).A total of 103 patients with ACMP complicated with HFREF admitted to our department from October 2016 to March 2020 were observed. Patients were divided into control group (50 cases) and experimental group (53 cases). The control group was given diuretic, vasodilator, and digitalis treatment, and the experimental group was supplemented with rhBNP treatment based on the control group. Patients' general information was collected. The levels of myocardial injury-associated indicators of patients were detected at and after admission.No significant differences were observed in the general data of patients compared with control group. The acute physiology and chronic health enquiry II score of patients was positively correlated with left ventricular ejection fraction (LVEF). At admission, the levels of myocardial injury indicators, N-terminal B-type brain natriuretic peptide, and cardiac ultrasound indexes had no significant difference between the control group and experimental group. However, after admission, the LVEF and stroke output levels were elevated, while the other indicators were all decreased compared with the control group.The rhBNP exerts a protective effect on ACMP-induced cardiomyocyte injury to improve cardiac function, shorten the length of hospital stay, and reduce the incidence and mortality of delayed encephalopathy after carbon monoxide poisoning.
2019-06-01 | Clinical Pearls in Medical Toxicology: Updates Ranging From Decontamination to Elimination
Such as any field of medicine, it is imperative to stay current with the latest advances and treatment modalities in toxicology. With the absence of rigorous randomized controlled trials, many updated guidelines are created by expert consensus and/or case reports and clinical experience. Over the past 10 years, there have been several changes in the management of drug overdoses in light of new data available. Although this is not a comprehensive review of all available antidotes, this article will focus on several important interventions including the use of gastrointestinal decontamination, hyperinsulinemic–euglycemic therapy, methylene blue, intravenous lipid emulsion, hemodialysis, and extracorporeal membrane oxygenation.
oligonucleotides
2023-11-06 | LncRNAs and CircRNAs as Strategies against Pathological Conditions Caused by a Hypoxic/Anoxic State
Brain damage can be induced by oxygen deprivation. It is known that hypoxic or anoxic conditions can lead to changes in the expression levels of non-coding RNAs (ncRNAs), which, in turn, can be related to Central Nervous System (CNS) injuries. Therefore, it could be useful to investigate the involvement of non-coding RNAs (ncRNAs), as well as the underlying mechanisms which are able to modulate them in brain damage induced by hypoxic or anoxic conditions. In this review, we focused on recent research that associates these conditions with long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). The results of this review demonstrate that the expression of both lncRNAs and circRNAs can be influenced by oxygen deprivation conditions and so they can contribute to inducing damage or providing neuroprotection by affecting specific molecular pathways. Furthermore, several experimental studies have shown that ncRNA activity can be regulated by compounds, thus also modifying their transcriptomic profile and their effects on CNS damages induced by hypoxic/anoxic events.
2023-04-18 | LncRNA CRNDE binds hnRNPA1 to facilitate carbon monoxide poisoning-induced delayed encephalopathy via inhibiting UCHL5-mediated SMO deubiquitination.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is one of the most common complications following carbon monoxide intoxication. Long noncoding RNAs (lncRNAs) exert critical functions in numerous neurological disorders. We intended to investigate the role of CRNDE in DEACMP. The DEACMP model in rats and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC-12 cells were established. Brain and cell injuries were assessed with H&E staining, Nissl staining, TUNEL and CCK8 assays, respectively. Related proteins and RNAs were quantified with western blot and qRT-PCR. The N6-methyladenosine (m6A) level was determined using MeRIP-qPCR and immunofluorescence. Loss and gain function studies were performed to investigate the biological function of CRNDE. The potential mechanisms between each factor were explored using RNA immunoprecipitation, RNA-pull down and co-immunoprecipitation. CRNDE was increased in the hippocampal tissues of DEACMP rats and in OGD/R-treated PC-12 cells, which was positively correlated to m6A modification. Knockdown of CRNDE reduced cell damage and elevated UCHL5 and SMO expressions in OGD/R-treated PC-12 cells. hnRNPA1 was upregulated in DEACMP. In addition, inhibiting hnRNPA1 prevented apoptosis in PC-12 cells subjected to OGD/R. hnRNPA1 bound to CRNDE and remained in the nucleus, which inhibited UCHL5 expression through the formation of CRNDE-hnRNPA1-mRNA complex. UCHL5 could inhibit SMO ubiquitination and suppress PC-12 cell apoptosis during OGD/R. CRNDE silencing blocked brain injury in DEACMP, while knocking down UCHL5 reversed these effects. CRNDE interacted with hnRNPA1 to facilitate DEACMP via inhibition of UCHL5-mediated SMO deubiquitination. CRNDE might be a latent therapeutic target for treating DEACMP.
2022-09-29 | LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3β/β-catenin Pathway via miR-212-5p.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague-Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen-glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3β/β-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3β/β-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3β/β-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.
other
2025-07-14 | Reciprocal regulation of GPNMB/HIF-1α for Inhibition of neuronal ferroptosis in delayed encephalopathy after acute carbon monoxide poisoning.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most common complication after acute carbon monoxide (CO) poisoning. However, the pathogenesis of DEACMP remains ambiguous. The neuroprotective role of GPNMB has been observed in amyotrophic lateral sclerosis and Parkinson's disease. GPNMB was elevated in the brain tissues of DEACMP rats, while its function in DEACMP remains unclear. In this study, a CO poisoning rat model and oxygen-glucose deprivation (OGD)-treated PC-12 cells were established as an in vivo and in vitro DEACMP model, respectively. The ferroptosis inhibitor Ferrostatin-1 (Fer-1) ameliorated cognitive impairment, inflammation and oxidative stress of rats with DEACMP as assessed by Morris Water Maze test, ELISA assay and commercial kits of oxidative markers. Immunofluorescence, qRT-PCR or western blot showed that GPNMB was elevated in CA1 hippocampal tissues of CO-poisoned rats. Additionally, TUNEL staining, ELISA assay and western blot revealed that GPNMB rescued OGD-induced cell apoptosis, inflammation and ferroptosis in PC-12 cells. Mechanistical study showed that STAT3 was a transcriptional activator of GPNMB as detected by luciferase and ChIP assays, and co-immunoprecipitation and immunofluorescence staining revealed that GPNMB stabilized HIF-1α by direct binding. Functionally, GPNMB protected against OGD-induced impairments via inducing HIF-1α. Furthermore, GPNMB attenuated cognitive impairment, oxidative stress and neuronal ferroptosis of rats with DEACMP. In conclusion, GPNMB/HIF-1α exhibited neuroprotective effects via suppressing ferroptosis in DEACMP.
2024-03-15 | Delayed encephalopathy after acute carbon monoxide poisoning: a case study.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a relatively rare inflammatory-associated neurometabolic complication. In this article, we present a case report of a 50-year-old male patient with a history of carbon monoxide poisoning. This acute poisoning, although successfully controlled during a stay in the intensive care unit of a local hospital, later led to persistent neurological symptoms. The patient was then treated in the inpatient unit of the rehabilitation clinic, where cognitive deterioration began to develop 20 days after admission. Subsequent examination using EEG and magnetic resonance imaging confirmed severe encephalopathy later complicated by SARS-CoV-2 infection with fatal consequences due to bronchopneumonia. Because currently there are no approved guidelines for the management of DEACMP, we briefly discuss the existing challenges for future studies, especially the application of rational immunosuppressive therapy already in the acute treatment phase of CO poisoning, which could prevent the development of a severe form of DEACMP.
small molecules
2026-05-07 | Acupuncture for the treatment of Delayed Encephalopathy after Acute Carbon Monoxide Poisoning: a case report.
Delayed Encephalopathy after Acute Carbon Monoxide Poisoning (DEACMP) is characterized by delayed neuropsychiatric deterioration after a period of apparent recovery. Effective treatments remain limited. A 75-year-old male developed cognitive decline, motor dysfunction, incontinence, and sleep disturbance persisting for more than 3 months after carbon monoxide poisoning despite standard therapy. MRI showed diffuse white matter demyelination. Zhu's scalp acupuncture combined with body acupuncture was administered once daily for 15 sessions. Baseline MMSE and AD8 were not testable due to severe disorganized speech and poor cooperation. After treatment initiation, MMSE improved from 11 (after 1 session) to 14 (after 3 sessions), 24 (after 15 sessions), and 26 at one-month follow-up. AD8 decreased from 7 to 5, 2, and 1 at the corresponding time points. Functional independence was restored. No adverse events were reported. The temporal pattern of improvement suggests a possible association between acupuncture intervention and neurological recovery. Controlled studies are needed to further evaluate efficacy.
2026-04-04 | The role of sGC-cGMP-PKG signaling pathway-mediated excitotoxicity in delayed encephalopathy after carbon monoxide poisoning.
This study investigated the role of soluble guanylate cyclase-cyclic guanosine monophosphate-protein kinase G (sGC-cGMP-PKG) signaling pathway in the regulation of carbon monoxide (CO) on glutamate neurotransmitter system and neuronal excitotoxicity in vitro and in vivo, and revealed the possible mechanism of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). The results showed that compared with the control group, a large number of apoptotic cells appeared in the hippocampus of mice 7 and 14 days after CO exposure, and the learning and spatial memory functions were decreased. The protein expression levels of heme oxygenase-1 (HO-1), sGC, PKG, N-methyl-D-aspartate receptor 2 A (NR2A) and N-methyl-D-aspartate receptor 2B (NR2B) and the concentrations of glutamate, cGMP and calcium ion (Ca²⁺) were significantly increased at different time points after CO exposure. At the same time, in the in vitro model of acute CO poisoning, the expression of HO-1, sGC, PKG, NR2A and NR2B in PC12 cells exposed to different concentrations of CO increased, glutamate release increased, Ca²⁺ overload, excitotoxicity, and then led to cell apoptosis. After treatment with sGC specific inhibitor, the expression level of N-methyl-D-aspartate (NMDA) receptor protein and Ca²⁺ concentration were significantly decreased, the number of apoptotic cells was significantly decreased, and the animal behavior related indicators were improved. The results of the present study suggest that excitotoxicity mediated by sGC-cGMP-PKG signaling plays an important role in DEACMP induced by CO poisoning.
2026-02-23 | Optimizing hyperbaric oxygen initiation time in carbon monoxide poisoning: a 3-hour window enhances neurological recovery via lactate clearance.
To explore the optimal initiation time of hyperbaric oxygen therapy (HBOT) for moderate-to-severe acute carbon monoxide poisoning (ACOP) and to assess the prognostic value of lactate clearance and early MRI findings. This single-center retrospective study included 12 ACOP patients (2020-2023) treated with HBOT within 6 h after admission. Patients were categorized by HBOT initiation time: early (≤3 h, n=8) and delayed (>3 h, n=4). Clinical, biochemical, and imaging data were analyzed. Primary outcomes were time to regain consciousness and Barthel Index at 6 months. Median HBOT initiation was 112 min. Early treatment was associated with faster organ function recovery (greater SOFA score reduction, p<0.05). Lactate normalized within a median of 17.5 h, and clearance >50 % in 24 h correlated with better neurological outcomes (p=0.002). MRI detected early globus pallidus injury more sensitively than CT. At 6 months, 83.3 % recovered functionally; one developed delayed encephalopathy. Early HBOT initiation (≤3 h) may facilitate metabolic and neurological recovery in ACOP. Early lactate clearance and MRI findings may serve as prognostic markers. Given the small sample size and absence of a non-HBOT control group, these results are exploratory and require confirmation in larger studies.
2025-11-30 | High-density lipoprotein cholesterol protects against delayed encephalopathy after acute carbon monoxide poisoning.
High-density lipoprotein cholesterol (HDL-C) plays a crucial role in neurological disorders. In this study, we aimed to elucidate the role of HDL-C in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), which presents with both neurological and psychiatric symptoms. Two-sample Mendelian randomization was employed on 201 lipid summary statistics to investigate potential causality. Data from the FinnGen database of 306,787 individuals were used. Mendelian randomization analysis results were screened using Bayesian model averaging. The results were validated in a multicenter cohort of 1368 patients, and the role of the antioxidant properties of high-density lipoprotein in DEACMP was examined. Mendelian randomization analysis identified six high-density lipoprotein-related variants significantly associated with DEACMP, with the cholesterol to total lipids ratio in medium high-density lipoprotein showing the strongest effect (marginal inclusion probability = 0.51, p = 1.00 × 10-3, false discovery rate = 6.00 × 10-3). Clinical validation confirmed HDL-C as an independent protective factor. Patients without DEACMP had higher high-density lipoprotein oxidant index values (1.23 [interquartile range: 1.02-1.36]) than those who developed DEACMP (0.84 [interquartile range: 0.66-0.90]); the high-density lipoprotein oxidant index declined significantly in postmenopausal women (p = 0.023). These findings demonstrate that HDL-C mitigates the risk of DEACMP through its antioxidant capacity. The integration of genetic evidence, clinical validation, and functional assays provides robust support for HDL-C as a predictive biomarker of neural recovery after carbon monoxide poisoning.
2025-11-09 | Axin-1, modified by IGF2BP2-dependent m6A, triggers neuronal ferroptosis in delayed encephalopathy animal model caused by carbon monoxide poisoning via Smurf1-mediated BDNF ubiquitination.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a common complication after carbon monoxide poisoning. This study focused on the role and mechanism of Axin-1 regulating ferroptosis in DEACMP. Nissl staining, immunohistochemistry, immunofluorescence and Prussian blue were used to evaluate the histopathology and iron distribution of DEACMP rats. The N6-methyladenosine (m6A) level of Axin-1 was analyzed by m6A-RNA immunoprecipitation and qPCR (MeRIP-qPCR). The mRNA and protein levels of the molecules were tested by RT‑qPCR and Western blot. RNA immunoprecipitation (RIP) and Co-immunoprecipitation (Co-IP) experiments were used to verify the interaction between molecules. Cell viability and apoptosis were detected using Cell counting kit-8 (CCK-8) and Terminal deoxynucleotidyl transferase dUTP nick (TUNEL) staining. Reactive oxygen species (ROS) levels were measured by flow cytometry. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), and Fe2+ were evaluated by biochemical kits. The expression of Axin-1 in DEACMP rats was increased, and its up-regulation was related to IGF2BP2-mediated m6A modification. Overexpression of Axin-1 abolished the protective inhibition of IGF2BP2 depletion-mediated oxidative damage and ferroptosis induced by oxygen and glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Axin-1 promoted the ubiquitination and degradation of BDNF by targeting Smurf1. Overexpressed Axin-1 inhibited the protective effect of BDNF on oxidative damage and ferroptosis. The Nrf2/HO-1 pathway played a role in OGD/R-triggered ferroptosis, which was mediated by Axin-1. The IGF2BP2/Axin-1 axis also regulated ferroptosis in vivo. IGF2BP2-mediated m6A modification of Axin-1 promoted oxidative damage and neuronal ferroptosis by modulating Smurf1/BDNF and Nrf2/HO-1 pathways in DEACMP animal model and OGD/R cell model. Therefire, Axin-1 may be a potential therapeutic target for the treatment of DEACMP.
cell therapies
2021-10-21 | BMSC-derived Exosomes Protect Against Delayed Encephalopathy after Acute Carbon Monoxide Poisoning in Rats via Blockade of Notch Signaling
Abstract Objective: Our aim was to probe the therapeutic effect by which (BMSC-ex) protect against (DEACMP) in rat models in vivo. Methods: BMSC-ex were successfully characterized and proven to pass the blood brain barrier and migrate to the injured brain area. Rats were randomly divided into six groups and the cognitive function of mice was evaluated by the morris water maze. The severity of pathological changes was evaluated by HE staining and LFB staining. The expression of cytokines was detected by ELISA. Immunohistochemical staining and western blot analysis were utilized to detect the protein expression of Foxp3、CD4、MBP、Notch1 and Hess1 in brain tissue.Results: We found that BMSC-ex significantly reduced inflammation, increased the levels of (Tregs), relieved demyelination, and ameliorated the cognitive impairment in DEACMP rats. Furthermore, inhibiting the Notch pathway led to a partial reversal of the effect of BMSC-ex in mice.Conclusions: BMSC-ex relieved the severity of demyelination in the DEACMP rat models by regulating Tregs subsets and the expression of Notch signaling. Hence BMSC-ex play a protected role in DEACMP by upregulating Tregs and the regulatory components of Notch signaling and this may provide a new clinical strategy for the treatment of DEACMP patients.
2013-08-01 | Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication
Abstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs) to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI). The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy. Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE
2010-10-26 | Treatment of acute carbon-monoxide poisoning with therapeutic erythrocytapheresis: Clinical effects and results in 17 victims
Seventeen cases of acute carbon-monoxide poisoning were treated with therapeutic red cell-exchange. Glasgow Coma Scale score was used to evaluate the level of consciousness. The mean carboxyhemoglobin level decreased from 0.286 ± 0.1805 (28.6 ± 18.05%) to 0.0613 ± 0.0418 (6.13 ± 4.18%) and Glasgow Coma Scale score increased from 10 ± 3 to 13.76 ± 1.89. While 11 patients scored 15 at the end of the treatment, four scored 15 in an hour after the treatment. None of the patients died. Two victims (11.7%) experienced ischemic encephalopathy. Therapeutic red cell-exchange therapy can be an effective treatment in reducing mortality and morbidity in carbon-monoxide poisoning.
2009-05-05 | Structural and functional improvement of injured brain after severe acute carbon monoxide poisoning by stem cell-based therapy in rats.
We investigated the feasibility and efficacy of bone marrow mesenchymal stem cells (BMSCs)-derived neural stem-like cells (MS-NSCs) therapy on injured brain in rats after severe acute carbon monoxide (CO) poisoning. Controlled animal study. Research laboratory of a university hospital. Sprague-Dawley rats weighing 230 +/- 20 g and 90 +/- 10 g. The rats were exposed to 1000 ppm CO in air for 40 minutes and then to 3000 ppm for another 20 minutes until they lost consciousness. Approximately 7 x 10 allogeneic BMSCs or MS-NSCs labeled with BrdU were infused into the poisoned rats via the internal carotid after a 24-hour resuscitation. The rats with and without CO poisoning were used as placebo and sham controls, respectively. The neurologic and cognitive functions were evaluated by Neurologic Severity Scores and Morris water maze tests. Examinations with immunohistochemistry, myelin, and hematoxylin-eosin staining were made to assess cerebral structure after 5 weeks. Histologically, the compactness and arrangement of the insulted white matter were improved by the cellular treatments. The transplanted MS-NSCs were positive for microtubule-associated protein 2 in hippocampus, 84.6% +/- 5.6%, and for glial fibrillary acidic protein in subventricular white matter and hippocampus, 32.2% +/- 2.5% and 9.7% +/- 1.2%, respectively, although the MS-NSCs group showed a larger fraction in the expression of the above markers in corresponding domains compared with the BMSCs group. The MS-NSCs also displayed a higher survival rate than BMSCs in most domains of diffusively injured brain, leading to a better improvement in the Morris water maze test (p < 0.05). The stem cell-based therapy could be advantageous for improving the structure and function of injured brain in rats after severe acute CO poisoning, indicating the potential use as a novel approach for severely CO-poisoned patients with delayed neurologic sequelae. Furthermore, MS-NSCs may render better therapeutic effects after neurologic injury than untreated BMSCs.
2009-05-01 | HEMOGLOBIN VESICLES AND RED BLOOD CELLS AS CARRIERS OF CARBON MONOXIDE PRIOR TO OXYGEN FOR RESUSCITATION AFTER HEMORRHAGIC SHOCK IN A RAT MODEL
Hemoglobin vesicles (HbVs) are artificial oxygen (O2) carriers that encapsulate concentrated hemoglobin (Hb) solution in phospholipid vesicles (liposomes). Recent reports on cytoprotective effects of exogenous carbon monoxide (CO) urged us to test infusion of CO-bound HbV (CO-HbV) and red blood cells (CO-RBC) in hemorrhagic-shocked rats to improve tissue viability over that of O2-bound HbV (O2-HbV) and O2-bound RBC (O2-RBC). Male Wistar rats were anesthetized with 1.5% sevoflurane inhalation (FiO2 = 21%) while spontaneous breathing was maintained. Shock was induced by 50% blood withdrawal from femoral artery. Fifteen minutes later, they received CO-HbV, CO-RBC, O2-HbV, O2-RBC, or empty vesicles (EV) suspended in 5% recombinant albumin. All groups showed prompt recovery of blood pressure and blood gas parameters just after resuscitation and survived for 6 h of observation period. However, only the EV group showed significant hypotension at 3 and 6 h. Plasma enzyme levels were elevated at 6 h, especially in the O2-HbV, O2-RBC, and EV groups. They were significantly lower in the CO-HbV and CO-RBC groups than in the O2-bound fluids. Immunohistochemical staining of 3-nitrotyrosine exhibited less oxidative damage in the liver and lung for CO-HbV and CO-RBC groups. Blood carbonyl Hb levels (26%-39% immediately after infusion) decreased to less than 3% at 6 h while CO was exhaled through the lung. Both HbV and RBC gradually gained the O2 transport function. Collectively, both CO-HbV and CO-RBC showed a resuscitative effect for hemorrhagic-shocked rats. They reduced oxidative damage to organs in comparison to O2-HbV and O2-RBC. Adverse and poisonous effects of CO gas were not evident for 6 h in this experimental model. Further study is necessary to clarify the neurological impact of a longer observation period for eventual clinical applications. ABBREVIATIONS-Hb-hemoglobin; HbV-Hb vesicles; CO-HbV-CO-bound HbV; RBC-red blood cell; CO-RBC-CO-bound RBC; EV-empty vesicles; HO-heme oxygenase; HBOC-hemoglobin-based oxygen carrier; rHSA-recombinant human serum albumin; Hct-hematocrit; PaO2-arterial blood O2 tension; PaCO2-arterial blood CO2 tension; HR-heart rate; AST-aspartate aminotransferase; ALT-alanine aminotransferase; LDH-lactate dehydrogenase; Mb-myoglobin; NOS-nitric oxide synthase
proteins
2022-04-01 | Effect of Recombinant Human Brain Natriuretic Peptide on Acute Carbon Monoxide Poisoning Complicated with Heart Failure with Reduced Ejection Fraction.
This paper aims to observe the effect of recombinant human brain natriuretic peptide (rhBNP) on treatment of acute carbon monoxide poisoning (ACMP) complicated with heart failure with reduced ejection fraction (HFREF).A total of 103 patients with ACMP complicated with HFREF admitted to our department from October 2016 to March 2020 were observed. Patients were divided into control group (50 cases) and experimental group (53 cases). The control group was given diuretic, vasodilator, and digitalis treatment, and the experimental group was supplemented with rhBNP treatment based on the control group. Patients' general information was collected. The levels of myocardial injury-associated indicators of patients were detected at and after admission.No significant differences were observed in the general data of patients compared with control group. The acute physiology and chronic health enquiry II score of patients was positively correlated with left ventricular ejection fraction (LVEF). At admission, the levels of myocardial injury indicators, N-terminal B-type brain natriuretic peptide, and cardiac ultrasound indexes had no significant difference between the control group and experimental group. However, after admission, the LVEF and stroke output levels were elevated, while the other indicators were all decreased compared with the control group.The rhBNP exerts a protective effect on ACMP-induced cardiomyocyte injury to improve cardiac function, shorten the length of hospital stay, and reduce the incidence and mortality of delayed encephalopathy after carbon monoxide poisoning.
2019-06-01 | Clinical Pearls in Medical Toxicology: Updates Ranging From Decontamination to Elimination
Such as any field of medicine, it is imperative to stay current with the latest advances and treatment modalities in toxicology. With the absence of rigorous randomized controlled trials, many updated guidelines are created by expert consensus and/or case reports and clinical experience. Over the past 10 years, there have been several changes in the management of drug overdoses in light of new data available. Although this is not a comprehensive review of all available antidotes, this article will focus on several important interventions including the use of gastrointestinal decontamination, hyperinsulinemic–euglycemic therapy, methylene blue, intravenous lipid emulsion, hemodialysis, and extracorporeal membrane oxygenation.
oligonucleotides
2023-11-06 | LncRNAs and CircRNAs as Strategies against Pathological Conditions Caused by a Hypoxic/Anoxic State
Brain damage can be induced by oxygen deprivation. It is known that hypoxic or anoxic conditions can lead to changes in the expression levels of non-coding RNAs (ncRNAs), which, in turn, can be related to Central Nervous System (CNS) injuries. Therefore, it could be useful to investigate the involvement of non-coding RNAs (ncRNAs), as well as the underlying mechanisms which are able to modulate them in brain damage induced by hypoxic or anoxic conditions. In this review, we focused on recent research that associates these conditions with long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). The results of this review demonstrate that the expression of both lncRNAs and circRNAs can be influenced by oxygen deprivation conditions and so they can contribute to inducing damage or providing neuroprotection by affecting specific molecular pathways. Furthermore, several experimental studies have shown that ncRNA activity can be regulated by compounds, thus also modifying their transcriptomic profile and their effects on CNS damages induced by hypoxic/anoxic events.
2023-04-18 | LncRNA CRNDE binds hnRNPA1 to facilitate carbon monoxide poisoning-induced delayed encephalopathy via inhibiting UCHL5-mediated SMO deubiquitination.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is one of the most common complications following carbon monoxide intoxication. Long noncoding RNAs (lncRNAs) exert critical functions in numerous neurological disorders. We intended to investigate the role of CRNDE in DEACMP. The DEACMP model in rats and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC-12 cells were established. Brain and cell injuries were assessed with H&E staining, Nissl staining, TUNEL and CCK8 assays, respectively. Related proteins and RNAs were quantified with western blot and qRT-PCR. The N6-methyladenosine (m6A) level was determined using MeRIP-qPCR and immunofluorescence. Loss and gain function studies were performed to investigate the biological function of CRNDE. The potential mechanisms between each factor were explored using RNA immunoprecipitation, RNA-pull down and co-immunoprecipitation. CRNDE was increased in the hippocampal tissues of DEACMP rats and in OGD/R-treated PC-12 cells, which was positively correlated to m6A modification. Knockdown of CRNDE reduced cell damage and elevated UCHL5 and SMO expressions in OGD/R-treated PC-12 cells. hnRNPA1 was upregulated in DEACMP. In addition, inhibiting hnRNPA1 prevented apoptosis in PC-12 cells subjected to OGD/R. hnRNPA1 bound to CRNDE and remained in the nucleus, which inhibited UCHL5 expression through the formation of CRNDE-hnRNPA1-mRNA complex. UCHL5 could inhibit SMO ubiquitination and suppress PC-12 cell apoptosis during OGD/R. CRNDE silencing blocked brain injury in DEACMP, while knocking down UCHL5 reversed these effects. CRNDE interacted with hnRNPA1 to facilitate DEACMP via inhibition of UCHL5-mediated SMO deubiquitination. CRNDE might be a latent therapeutic target for treating DEACMP.
2022-09-29 | LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3β/β-catenin Pathway via miR-212-5p.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague-Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen-glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3β/β-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3β/β-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3β/β-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.
other
2025-07-14 | Reciprocal regulation of GPNMB/HIF-1α for Inhibition of neuronal ferroptosis in delayed encephalopathy after acute carbon monoxide poisoning.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most common complication after acute carbon monoxide (CO) poisoning. However, the pathogenesis of DEACMP remains ambiguous. The neuroprotective role of GPNMB has been observed in amyotrophic lateral sclerosis and Parkinson's disease. GPNMB was elevated in the brain tissues of DEACMP rats, while its function in DEACMP remains unclear. In this study, a CO poisoning rat model and oxygen-glucose deprivation (OGD)-treated PC-12 cells were established as an in vivo and in vitro DEACMP model, respectively. The ferroptosis inhibitor Ferrostatin-1 (Fer-1) ameliorated cognitive impairment, inflammation and oxidative stress of rats with DEACMP as assessed by Morris Water Maze test, ELISA assay and commercial kits of oxidative markers. Immunofluorescence, qRT-PCR or western blot showed that GPNMB was elevated in CA1 hippocampal tissues of CO-poisoned rats. Additionally, TUNEL staining, ELISA assay and western blot revealed that GPNMB rescued OGD-induced cell apoptosis, inflammation and ferroptosis in PC-12 cells. Mechanistical study showed that STAT3 was a transcriptional activator of GPNMB as detected by luciferase and ChIP assays, and co-immunoprecipitation and immunofluorescence staining revealed that GPNMB stabilized HIF-1α by direct binding. Functionally, GPNMB protected against OGD-induced impairments via inducing HIF-1α. Furthermore, GPNMB attenuated cognitive impairment, oxidative stress and neuronal ferroptosis of rats with DEACMP. In conclusion, GPNMB/HIF-1α exhibited neuroprotective effects via suppressing ferroptosis in DEACMP.
2024-03-15 | Delayed encephalopathy after acute carbon monoxide poisoning: a case study.
Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a relatively rare inflammatory-associated neurometabolic complication. In this article, we present a case report of a 50-year-old male patient with a history of carbon monoxide poisoning. This acute poisoning, although successfully controlled during a stay in the intensive care unit of a local hospital, later led to persistent neurological symptoms. The patient was then treated in the inpatient unit of the rehabilitation clinic, where cognitive deterioration began to develop 20 days after admission. Subsequent examination using EEG and magnetic resonance imaging confirmed severe encephalopathy later complicated by SARS-CoV-2 infection with fatal consequences due to bronchopneumonia. Because currently there are no approved guidelines for the management of DEACMP, we briefly discuss the existing challenges for future studies, especially the application of rational immunosuppressive therapy already in the acute treatment phase of CO poisoning, which could prevent the development of a severe form of DEACMP.
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Drug Discovery Landscape
1 orphan drug designation for Delayed encephalopathy due to carbon monoxide poisoning.
1 orphan drug designation for Delayed encephalopathy due to carbon monoxide poisoning.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
recombinant neuroglobin (rNgb) containing mutations H64Q/C46G/C55S/C120S | proteins | FDA | 2014-11-17 | — | University of Pittsburgh |
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