Neurological sequelae in acute carbon monoxide poisoning: A prospective observational study with MRI data.

OBJECTIVES: Acute carbon monoxide (CO) poisoning survivors may experience persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). This study evaluated the clinical features, laboratory results, acute brain lesions (ABLs) on diffusion-weighted imaging (DWI) at presentation, and long-term outcomes and explored differences between patients with PNS and DNS. METHODS: The study included 443 patients who had experienced CO poisoning, underwent DWI and completed 1-year follow-ups. The demographics, comorbidities, symptomatology, laboratory results, ABLs on DWI at presentation, and long-term outcomes were compared between patients with PNS and those with DNS. RESULTS: The 42 (9.5%) and 96 (21.7%) patients with PNS and DNS, respectively, showed no significant differences in demographics, duration of CO exposure, initial conscious level, symptomatology, and laboratory results. ABLs on DWI were observed in 33 patients (33/42) with PNS and 62 patients (62/96) with DNS. The most common region of ABLs was the globus pallidus (60.6% and 56.6% in PNS and DNS, respectively). The proportion of ABLs present and lesion distribution did not differ significantly between the two groups. At 1 year, a significantly higher proportion of patients in the PNS group showed a good outcome (defined as modified Rankin Scale [mRS] scores of 0-2, 81%) compared with the DNS group (81% vs. 56.3%, p = .047). CONCLUSION: Demographics, clinical features, laboratory results, and acute brain lesions on MRI at presentation did not differ between the PNS and DNS groups. However, the long-term outcome of PNS was better than that of DNS.

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC-treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 µm) and nitric oxide (100 µm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 µm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

The predictive value of neutrophil-lymphocyte ratio at presentation for delayed neurological sequelae in carbon monoxide poisoning.

OBJECTIVE: To explore the predictive value of neutrophil-lymphocyte ratio (NLR) at presentation for delayed neurological sequelae (DNS) in carbon monoxide (CO) poisoning. METHODS: This single-center retrospective observational study included a total of 253 consecutive patients who visited the emergency department (ED) due to acute CO intoxication between 7 October 2015 and 31 December 2019. The included patients had a history of coma and their blood routine was measured within one hour of ED admission. They were divided into two groups according to the presence of DNS, including those who developed DNS (DNS group) and those who did not (non-DNS group). RESULTS: A total of 171 patients were included in this research, and 49 (28.7%) developed DNS. The median NLR at ED admission was obviously higher in the DNS group (10.60 [9.69-15.34]) than in the non-DNS group (7.53 [5.86-8.56]) (p < 0.001). Multivariate analysis indicated that a high NLR (adjusted odds ratio (AOR): 1.78, 95% confidence interval (CI): 1.46-2.18) and the occurrence of acute brain lesions (AOR: 7.50, 95%CI: 2.86-19.68) on diffusion-weighted imaging were independent predictors of DNS. The NLR was more than 8.97. The prediction of occurrence of DNS had a sensitivity of 93.88% and a specificity of 84.43%. Kappa value was 0.713. The predicted results showed good authenticity and consistency. CONCLUSION: The level of NLR at presentation had good predictive value for the development of DNS, showing the superior value for clinical application.

Carbon monoxide increases utero-placental angiogenesis without impacting pregnancy specific adaptations in mice.

BACKGROUND: Cigarette smokers have a reduced risk of developing preeclampsia, possibly attributed to an increase in carbon monoxide (CO) levels. Carbon monoxide is a gasotransmitter that has been implicated in maintaining vascular tone, increasing angiogenesis, and reducing inflammation and apoptosis at physiological concentrations. Moderately increasing CO concentrations may have therapeutic potential to prevent or treat preeclampsia; however, the effects of CO on pregnancy are under studied. Our objective was to investigate the effect of CO on major angiogenic and inflammatory markers in pregnancy, and to evaluate the effect of CO on indicators of placental health. FINDINGS: Pregnant CD-1 mice were constantly exposed to either ambient air or 250 ppm CO from conception until gestation day (GD)10.5 or GD16.5. Using a qRT-PCR array, we identified that CO increased expression of major angiogenic genes at the implantation site on GD10.5, but not GD16.5. Pro-inflammatory cytokines in the plasma and tissue lysates from implantation sites in treated mice were not significantly different compared to controls. Additionally, CO did not alter the implantation site phenotype, in terms of proliferative capacity, invasiveness of trophoblasts, or abundance of uterine natural killer cells. CONCLUSIONS: This study suggests that CO exposure is pro-angiogenic at the maternal-fetal interface, and is not associated with demonstrable concerns during murine pregnancy. Future studies are required to validate safety and efficacy of CO as a potential therapeutic for vascular insufficiency diseases such as preeclampsia and intrauterine growth restriction.

Stroke Incidence in Survivors of Carbon Monoxide Poisoning in South Korea: A Population-Based Longitudinal Study.

BACKGROUND Carbon monoxide (CO) poisoning is a suspected risk factor for stroke. However, the association between stroke occurrence and carbon monoxide poisoning remains unclear. This nationwide study in Korea analyzed the incidence of stroke in survivors of CO poisoning. MATERIAL AND METHODS In this nationwide, population-based longitudinal study, the database of the Health Insurance Review and Assessment Service was searched to identify patients diagnosed with CO poisoning from 2012 to 2018. Their incidence of ischemic and hemorrhagic strokes, the patterns of stroke incidences, the annual incidence rates in sequential time, the standardized incidence ratio (SIR), and the effects of hyperbaric oxygen therapy (HBOT) were analyzed. RESULTS Of the 29 301 patients diagnosed with CO poisoning during the study period, 984 (3.36%) were diagnosed with stroke after CO poisoning, with approximately 50% occurring within 1 year after CO poisoning. The overall SIR for stroke was 19.49 (95% confidence interval [CI], 17.92-21.12) during the first year, decreasing to 5.64 (95% CI, 4.75-6.66) during the second year. Overall stroke hazard ratio (HR) in the patients admitted to the ICU for CO poisoning was 2.28 (95% CI, 1.19-2.27), compared with 2.35 (95% CI, 1.94-2.84) for ischemic stroke and 1.76 (95% CI, 1.11-2.78) for hemorrhagic stroke. Cumulative HRs did not differ between patients who were and were not treated with HBOT for stroke. CONCLUSIONS CO poisoning is a high-risk factor for the development of stroke, evidenced by high incidences of stroke after CO poisoning. Practical strategies for preventing stroke after CO poisoning are needed, because stroke after CO poisoning affects adults of almost all ages, significantly increasing their socioeconomic burden.

TDZD-8 alleviates delayed neurological sequelae following acute carbon monoxide poisoning involving tau protein phosphorylation.

Objective: Acute carbon monoxide （CO）poisoning can cause delayed neurological sequelae (DNS). Glycogen synthase kinase 3ß (GSK-3ß) /Tau protein pathway is reported to play a key role in neurological abnormalities. In the present study, we aimed to determine the role of GSK-3ß/Tau in DNS following acute CO poisoning.Methods: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a specific non-competitive inhibitor of GSK-3ß, was used to inhibit GSK-3ß. Twenty-four male Sprague-Dawley rats were randomly assigned to the three groups: Control group, CO group and CO-TDZD-8 group. Rats breathed 1000 ppm CO for 40 minutes and then 3000 ppm for up to 20 minutes until they lost consciousness. TDZD-8 (1 mg/kg) was administered intravenously three times after the end of CO exposure at 0, 24, 48 hours late. Learning and memory abilities were observed using the Morris Water Maze (MWM). Brain histological changes were evaluated by hematoxylin-eosin staining. Moreover, the expression levels of Tau and GSK-3ß were detected after acute carbon monoxide poisoning.Results: TDZD-8 significantly attenuated the learning and memory dysfunction induced by acute CO poisoning, ameliorated the histology structure of damaged neural cells in cortex and hippocampus CA1 area. TDZD-8 clearly decreased p-Tau expression, reversed the reduction of p-GSK-3ß induced by acute CO poisoning.Conclusions: The therapeutic effect of TDZD-8 in alleviating DNS caused by acute CO poisoning is related to the inactivation of Tau by intensifying the level of GSK-3ß phosphorylation.

Exposure Duration and History of Hypertension Predicted Neurological Sequelae in Patients with Carbon Monoxide Poisoning.

BACKGROUND: Carbon monoxide poisoning (COP) accounts for a large number of emergency department visits worldwide and is fatal in many cases. In surviving patients, neurological sequelae (NS) attributable to cerebral hypoxia are the most devastating outcome, but reliable predictors are limited. Therefore, we conducted a study to identify predictors of NS in patients with COP and evaluate their effects. METHODS: In this retrospective case-control study, we identified patients with COP in a medical center in Southern Taiwan between January 2005 and December 2014. Cases were patients with NS, and controls were patients without NS. We obtained information on potential predictors of NS from medical records and evaluated their association with NS, including demographic characteristics, exposure source, suicide attempts, duration of exposure (by tertile), histories, symptoms, signs, laboratory data, treatment, and the length of hospital stay. RESULTS: We included 371 patients with COP. Of them, 93 developed NS, and their mean ages (41.4 ± 14.7 years vs. 39.7 ± 14.2 years) and proportions of males (59.1% vs. 58.6%) were similar to those in the 298 controls. Multivariate logistic regression showed that a history of hypertension (adjusted odds ratio = 2.1; 95% confidence interval = 1.0, 4.5) and a longer duration of carbon monoxide exposure (adjusted odds ratio = 1.7; 95% confidence interval = 1.1, 2.8; the longest tertile [>5 hours] vs. the other two tertiles [≤5 hours]) were independent predictors for NS, but not the level of carboxyhemoglobin. CONCLUSIONS: This study identified two independent predictors for NS that may be useful for public healthcare workers and physicians in predicting outcomes and deciding on treatment strategies for COP patients.

Evaluation of changes in magnetic resonance diffusion tensor imaging after treatment of delayed encephalopathy due to carbon monoxide poisoning.

Diffusion tensor imaging of the brain tissue microstructure was performed to predict or diagnose the pathophysiological mechanism underlying delayed encephalopathy after carbon monoxide poisoning and the treatment effect was analyzed. The changes in the diffusion parameters (average diffusion coefficient and fractional anisotropy) in adult patients after hyperbaric oxygen therapy of delayed encephalopathy after carbon monoxide poisoning were not significant differences of the two lateral ventricles or anterior or posterior limb of the internal capsule. In the group exposed to hyperbaric oxygen therapy, the fractional anisotropy values of the white matter in the ventricles of the brain and anterior and posterior limbs of the internal capsule were higher than those recorded before therapy, while the average diffusion coefficient values were significantly lower. These finding provide important monitoring indicators for clinicians.

Pathology of carbon monoxide poisoning in two cats.

BACKGROUND: Carbon monoxide (CO), a common cause of poisoning in human beings has also been implicated in the death of animals. Though there are multiple studies on CO poisoning and relevant lethal blood COHb concentrations in humans, there are no reliable reports of diagnostic lethal carboxyhemoglobin percentage of saturation (COHb%) in cats. Additionally, due to shared housing environments, exposures to companion animals can be a surrogate for lethal exposures in human beings and provide valuable information in concurrent forensic investigations. CASE PRESENTATION: Two adult Singapura brown ticked cats were submitted to the California Animal Health and Food Safety Laboratory (CAHFS) for necropsy and diagnostic work-up. These animals were found dead along with their two deceased owners. Similar lesions were observed in both cats. At necropsy, gross lesions consisted of multifocal, large, irregular, bright red spots on the skin of the abdomen and the inner surface of ear pinnae, bright red muscles and blood. The carcasses, and tissues fixed in formalin retained the bright red discoloration for up to two weeks. Microscopic lesions included diffuse pulmonary congestion and edema, and multifocal intense basophilia of cardiomyocytes mostly affecting whole fibers or occasionally a portion of the fiber. Based on the clinical history,gross and microscopic changes, cyanide or carbon monoxide poisoning was suspected. Blood samples analyzed for carbon monoxide showed 57 and 41% carboxyhemoglobin COHb%. Muscle samples were negative for cyanide. CONCLUSION: There are no established reference values for lethal COHb concentration in cats. The COHb % values detected in this case which fell within the lethal range reported for other species, along with the gross lesions and unique histological findings in the heart suggest a helpful criteria for diagnosis of CO intoxication associated death in cats. This case demonstrates that since pets share the same environment as human beings and often are a part of their activities, they can be useful adjuncts in potential forensic investigations to help solve human cases.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.

Modulation of JAK2, STAT3 and Akt1 proteins by granulocyte colony stimulating factor following carbon monoxide poisoning in male rat.

Carbon monoxide (CO) is an odorless, colorless, tasteless and non-irritating by-product of inefficient combustion of hydrocarbon fuels such as motor vehicle exhausted gases. It is the leading cause of mortality in the USA among all unintentional toxicants. Male rats exposed to CO poisoning in the heart has many cardiovascular effects such as, cardiomyopathy, tachycardia, arrhythmias, and ischemia and in severe cases, myocardial infarction (MI) and cardiac arrest. Cardiomyocyte apoptosis is one of the most frequent consequences in the heart. Granulocyte colony stimulating factor (G-CSF) is a cytokine that mobilizes and differentiates granulocytes from stem cells. It can stimulate many anti-apoptotic pathways such as JAK2-STAT3 and PI3-Akt kinases following cardiac ischemia. G-CSF exerts its anti-apoptotic effects through binding to its specific cell surface receptor. The purpose of this study was to elucidate the mechanism of anti-apoptotic effect of G-CSF following CO poisoning. Rats were exposed to CO 1500 or 3000 ppm for 60 min. Animals received G-CSF 100 µg/kg subcutaneously for five consecutive days after CO intoxication. Western blot analysis was used to evaluate the expression of six proteins namely JAK2, p-JAK2, STAT3, p-STAT3, Akt1 and p-Akt1 following G-CSF 100 µg/kg consecutive dose administration after CO poisoning. There was a significant difference between phosphorylated proteins including p-JAK2, p-STAT3 and p-Akt1 in the G-CSF groups and those in control groups and there were not any significant differences in total protein among the groups.

Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning.

Assessment of Functional Disturbances in the Central Nervous System Caused by Severe Carbon Monoxide Poisoning in Rats.

An experimental model was developed for assessment of disturbances in CNS functions of laboratory animals caused by severe carbon monoxide poisoning. Normalization of the state of experimental rats after acute poisoning was accompanied by the development of cognitive abnormalities. Disturbances in the long-term memory were observed on days 1 and 14 after CO poisoning, while abnormalities in the short-term memory developed on days 1, 7, and 14. Learning impairment were recorded on day 8, while the training course began on day 7.

Transplantation of olfactory ensheathing cells attenuates acute carbon monoxide poisoning-induced brain damages in rats.

In this study, the therapeutic effect of olfactory ensheathing cells (OEC) transplantation on brain damage was evaluated on acute carbon monoxide (CO) poisoning rat model. Two weeks after primary culture, OECs were microinjected into hippocampus of CO poisoning rats. Survival of OECs in the host was observed and quantified. OECs survived at 2 weeks, but surviving cell number was found sharply decreased at 6 weeks and reduced to less than 10(3) at 8 weeks after transplantation. At 2 weeks after transplantation, motor function test and cerebral edema assay were performed and followed by pathological examination including hematoxylin and eosin and immunohistochemistry staining to observe the neuron injury and synapsin I and growth associated protein-43 (GAP-43) expression. Furthermore, biomarkers of oxidative stress and apoptosis related proteins in the hippocampus were detected. The results showed that CO exposure led to neurological dysfunction and cerebral edema in rats. After OEC transplantation, neurological function was significantly improved and the cerebral edema was alleviated. In addition, the numbers of neurons and Nissl bodies were increased and synapsin I and GAP-43 protein expressions were upregulated in the hippocampus. Compared with CO poisoned rats, superoxide dismutase activity and glutathione content were both increased and methane dicarboxylic aldehyde level was decreased in the hippocampus of OEC transplanted rats. Moreover, OEC transplantation reduced apoptosis induced by CO exposure. The Bcl-2 expression was significantly upregulated and Bax expression was significantly downregulated. The activity of caspase-3 and the cleaved-poly ADP-ribose polymerase expression were decreased. Taken together, our data suggest that OEC attenuates brain damages induced by acute CO poisoning within 2 weeks after transplantation.

Relationship between carbon monoxide intoxication and sister chromatid exchange in lymphocytes.

AIM: Carbon monoxide (CO) intoxication can be serious and is reported to be the cause of more than half of all fatal intoxications. In this study, we aimed to identify its genotoxic effects based on sister chromatid exchange (SCE). MATERIALS AND METHODS: CO-poisoned patients presented to the emergency services department were identified. Their demographic characteristics, vital findings, laboratory markers, source of CO gas, risk factors, and smoking habits were recorded. The genotoxic effect was assessed using the SCE method. RESULTS: A total of 38 patients were recruited. Their ages ranged from 16-64 years (mean: 29.79 ± 10.92 years). In all the cases, the source of CO gas was a flash heater. The mean carboxyhemoglobin (COHb) level was 25.05 ± 7.15%. Of all the patients, 12 (31.6%) had a the Glasgow Coma Scale (GCS) scores of less than 15, and an important negative correlation was found between the GCS and COHb level (r = -0.825; p < 0.001). Genotoxicity investigations revealed a significantly higher SCE frequency among patients with high COHb levels compared with that of control subjects with physiological COHb levels (p < 0.001). However, no correlation between increased SCE frequency and COHb level was found (r = 0.16; p = 0.34). CONCLUSION: CO poisoning was shown to result in genotoxicity via an increase in the frequency of SCE. This study is the first to demonstrate a genotoxic effect of CO independent of other chemicals.

Forensic aspects of carbon monoxide poisoning by charcoal burning in Denmark, 2008-2012: an autopsy based study.

Carbon monoxide (CO) inhalation is a well-known method of committing suicide. There has been a drastic increase in suicide by inhalation of CO, produced from burning charcoal, in some parts of Asia, and a few studies have reported an increased number of these deaths in Europe. CO-related deaths caused by charcoal burning have, to our knowledge, not been recorded in the Danish population before. In this retrospective study we present all autopsied cases of CO poisoning caused by charcoal burning in the period 2008-2012. 19 autopsied cases were identified, comprising 11 suicides, 4 accidents, and 2 cases of maternal/paternal filicide-suicide. The mean age of decedents was 38.2 years and the majority of the decedents were men. In 16 cases carboxyhemoglobin levels were above 50 % and in 14 cases we found distinctive cherry red livor mortis. Various concentrations of ethanol and drugs were found in 9 cases. Data suggest that this method of death has increased significantly in Denmark. Therefore, it is highly relevant to draw attention to the subject, to increase awareness as well as prevent future escalation.

[Unusual findings in carbon monoxide-related deaths]. / Ungewöhnliche Aspekte im Zusammenhang mit tödlich verlaufenen Kohlenmonoxidintoxikationen.

The authors present three cases of carbon monoxide poisoning (two suicides and one accident) from the autopsy material of the Institute of Legal Medicine at Basel, which are unusual with regard to the circumstances at the scene of death, the method of suicide and the post-mortem findings: Suicide of a 27-year-old male by burning charcoal in the bathroom, documentation of the suicide and previous attempted suicides on a tablet PC. Suicide of a 27-year-old male by carbon monoxide chemically, produced by dehydration of formic acid with sulphuric acid and inhalation of the gas through a breathing mask. Accidental carbon monoxide poisoning of a 34-year-old male by car exhaust fumes in an open garage. Difficult establishment of the diagnosis in the post-mortem examination due to unspecific colour of livores and varnished fingernails.

Carbon monoxide related deaths: A Verona case series. When cooperation becomes compulsory.

INTRODUCTION: Carbon monoxide (CO) poisoning is a significant concern in forensic medicine, as it often presents unique challenges in terms of diagnosis, investigation, and determination of the cause of death. CO is a colourless, odourless, and tasteless gas that can be lethal when inhaled in high concentrations. It binds strongly to haemoglobin, forming carboxyhaemoglobin (COHb), which reduces the oxygen-carrying capacity of the blood, leading to tissue hypoxia and ultimately death. MATERIALS AND METHODS: Circumstantial data, medical history information, autopsy findings, and toxicological analysis results related to 24 CO poisoning cases at the Institute of Legal Medicine in Verona were collected and analysed. The data were examined in an integrated manner to identify correlations and common patterns. A comparison was also made with the data available in the literature. RESULTS: The male gender was confirmed to be the most frequently involved. COHb levels were found to be less than 50% in 6 cases. Three individuals had concurrent cardiovascular pathologies, while 11 subjects tested positive for various substances, including alcohol, benzodiazepines, and morphine. In most cases, the manner of fatal intoxication was accidental, although 6 suicides and 1 homicide are reported. CONCLUSIONS: The Verona case series demonstrates that deaths due to CO poisoning require a multidisciplinary approach. The integration of diverse expertise is essential for assessing the manner of death. This approach enables a comprehensive evaluation of the available data, aids in distinguishing between accidental, suicidal, and homicidal deaths, and ensures accurate and reliable forensic conclusions.

Neuroprotective effects of erythropoietin in patients with carbon monoxide poisoning.

The purpose of this study was to evaluate the efficacy of erythropoietin (EPO) for treating patients with carbon monoxide (CO) poisoning. We conducted a randomized, prospective study of 103 patients with CO poisoning in two groups: an EPO group (n = 54; patients received EPO) and a placebo group (n = 49; patients received normal saline). The study endpoints were the functional outcome at day 30 (the Barthel index and neurologic sequelae), National Institutes of Health Stroke Scale (NIHSS) score, and the levels of S-100ß. At 18 days, the NIHSS score improved significantly and S-100ß levels significantly decreased in patients in the EPO group. At 30 days, patients in the EPO group had a superior Barthel index and fewer patients had delayed neurologic sequelae (DNS). This study demonstrated that early administration of EPO to patients with CO poisoning improved neurological outcomes and reduced the incidence of DNS.

The effect of granulocyte colony-stimulating factor administration on carbon monoxide neurotoxicity in rats.

Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel neuroprotective agent. Beneficial effects have been demonstrated by administrating G-CSF in different experimental stroke models. In this study, we evaluated the efficacy of G-CSF therapy on carbon monoxide (CO) neurotoxicity in rats exposed to acute CO poisoning. Immediately after exposure to 3,000 ppm of CO for 60 minutes, 50, 100, and 150 µg/kg of G-CSF or normal saline were administered to rats. Rats were sacrificed after 24 hours for serum marker analysis or 1 week for histopathological examination. Brain sections were stained with hematoxylin and eosin to assess leukocyte infiltration and hippocampal injury and with Luxol fast blue to assess demyelination. S100ß and glial fibrillary acidic protein (GFAP) serum levels were evaluated by commercial enzyme-linked immunosorbent assay kits. According to histopathological findings, G-CSF administration significantly restricted white-matter demyelination (150 µg/kg) (P = 0.006). Also, serum levels of S100ß in G-CSF-treated groups (100 and 150 µg/kg) decreased significantly (P < 0.01 and P < 0.05, respectively). In all does, G-CSF significantly reduced serum levels of GFAP (P < 0.01 for 50 µg/kg and P < 0.001 for other doses). Administration of G-CSF after CO poisoning attenuates brain cell damage through remyelination. G-CSF also decreases levels of related biomarkers, such as S100ß and GFAP.