Early predictors of brain injury in patients with acute carbon monoxide poisoning and the neuroprotection of mild hypothermia.

INTRODUCTION: Carbon monoxide (CO) poisoning can cause serious neurological sequelae. However, there is neither effective treatment strategy nor reliable indicators to determine the prognosis of patients with CO poisoning. The present study aimed to observe the changes of neurological function score, disease severity score, cerebral oxygen utilization (O2UCc), bispectral (BIS) index and neuron-specific enolase (NSE) concentration, and to elucidate the clinical significance of these potential indicators and the neuroprotective effect of mild hypothermia on brain injury in patients with severe acute CO poisoning. MATERIALS AND METHODS: A total of 277 patients with acute severe CO poisoning from 2013 to 2018 were enrolled in our hospital. Patients were divided into three groups according to their body temperature on the day of admission and their willingness to treat: a fever group (n = 78), a normal temperature group (NT group, n = 113), and a mild hypothermia group (MH group, n = 86). All patients were given hyperbaric oxygen therapy, while those in the MH group received additional mild hypothermia treatment. The severity of the disease, the neurobehavioral status, the incidence of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), and other indicators including BIS, O2UCc, NSE were further evaluated in all patients at given time-points. RESULTS: Mild hypothermia therapy improved the prognosis of patients with CO poisoning, significantly decreased the value of O2UCc and NSE, and up-regulated BIS. The incidence of DEACMP at 6 months was 27% in the fever group, 23% in the NT group, and 8% in the MH group. The values of Glasgow-Pittsburgh coma scale (G-P score), BIS index and NSE were closely related to the occurrence of DEACMP, the cutoff values were 12.41, 52.17 and 35.20 ng/mL, and the sensitivity and specificity were 79.3%, 77.6%, 79.3% and 67.6%, 89.5%, 88.6% in the receiver operating characteristic curve (ROC), respectively. CONCLUSIONS: Early mild hypothermia treatment could significantly reduce the severity of brain injury after CO poisoning, and might be further popularized in clinic. G-P scores, NSE and BIS index can be regarded as the prediction indicators in the occurrence and development of DEACMP. CLINICAL TRIAL REGISTRATION: The study protocol was granted from Qingdao University Research Ethics Committee (Clinical trial registry and ethical approval number: QD81571283).

Corrigendum to "Clinical Characteristics of Visual Dysfunction in Carbon Monoxide Poisoning Patients".

[This corrects the article DOI: 10.1155/2020/9537360.].

Clinical Characteristics of Visual Dysfunction in Carbon Monoxide Poisoning Patients.

PURPOSE: The aim of the present study was to analyze the clinical characteristics of visual dysfunction in patients with carbon monoxide (CO) poisoning. METHODS: A total of 436 patients with CO poisoning were enrolled in our hospital from October 2012 to December 2018, including 193 patients with moderate poisoning (MP group), 165 with severe poisoning (SP group), and 78 with delayed encephalopathy (DE group). The clinical characteristics of visual dysfunction in patients with CO poisoning were analyzed through the collection of medical history, regular physical examination, brain magnetic resonance imaging (MRI), ophthalmological examination, the National Eye Institute Visual Function Questionnaire (NEI-VFQ), and its influencing factors. RESULTS: Some patients in the three groups had visual dysfunction. The main ocular symptoms were local pain, eye movement disorder, and visual field defect. The key pathological factors were keratopathy, retinal nerve cell damage, optic nerve damage, retinal vascular disease, macular disease, and occipital visual center damage. The clinical symptoms of visual dysfunction after CO poisoning lasted for a long time (>12 months) and were not completely consistent with the positive results of the ophthalmological examination. A few sequelae of ophthalmology were still left after the help of medicine. CONCLUSION: The incidence of visual dysfunction in patients with CO poisoning was high, the clinical symptoms were rich and diverse, the duration of disease was long, and the prognosis was poor. Thus, the relevant ophthalmological examination and intervention treatment should be perfected as soon as possible.

Feasibility analysis of external application of Xiao-Shuan-San in preventing PICC-related thrombosis.

PURPOSE: We aim to analyze the feasibility of external application of Xiao-Shuan-Santo prevent peripherally inserted central catheter (PICC) -related thrombosis. METHODS: A total of 218 patients with PICC catheterization were randomly divided into a control group (n = 103) and a treatment group (n = 115). Patients in the treatment group received additional external application of Xiao-Shuan-San. The changes of coagulation index, the incidence of PICC-related thrombosis and other complications, and the maximum blood flow rate (Vmax) of axillary vein were observed at 1 day before catheterization and 30 days after PICC. RESULTS: At 30 days after PICC, the incidence of PICC-related thrombosis and other adverse events in the treatment group were obviously lower than that in the control group (P < 0.05), and the decreased Vmax value of axillary vein in the control group (11.75±1.91 cm/s) was more visible than that in the treatment group (14.63±3.03 cm/s), accompanied by a statistical significance (P < 0.05). CONCLUSIONS: External application of Xiao-Shuan-San could reduce the incidence of PICC-related thrombosis and other complications.

[Effects of N-butylphthalide on the expressions of calpain 1 and CaMK II in hippocampus in rats with acute severe carbon monoxide poisoning].

OBJECTIVE: To investigate the effects of N-butylphthalide (NBP) on cognitive function in acute severe carbon monoxide (CO) poisoning rats and its mechanism. METHODS: 120 health Sprague-Dawley (SD) rats were randomly divided into three groups (n = 40): normal control group (NC group), CO poisoning group (CO group) and NBP treatment group (NBP group). The acute severe CO poisoning model was established in a hyperbaric oxygen chamber by intoxicated with 1 000 ×10-6 CO for 40 minutes, followed with 3 000 ×10-6 CO for another 20 minutes, and then received hyperbaric oxygen therapy 1.5 hours once a day until sacrificed. Rats in NBP group were administered orally NBP 60 mg/kg for 2 times daily until death. NC group and CO group were treated with equal amount of pure olive oil. Four rats in each group were taken from 1, 3, 7, 14, 30 days after model setup, respectively. The cognitive function score was assessed by Morris water maze test. The changes in ultrastructure of hippocampus were observed under transmission electron microscope. The expressions of calpain 1 and Ca2+/calmodulin dependent protein kinase II (CaMK II) in hippocampus of brain tissue were detected by immunofluorescence staining, and the localization of the two target proteins in neurons was observed by immunofluorescence double staining. RESULTS: Compared with NC group, the escape latency at 1 day after poisoning in CO group was significantly prolonged (s: 55.6±3.2 vs. 44.5±3.5, P < 0.05), and the times of the platform crossing was significantly decreased (times: 1.3±0.8 vs. 6.6±1.2, P < 0.05); the ultrastructure of hippocampus was obviously injured; the protein expressions of calpain 1 and CaMK II in brain tissue were significantly increased at 1 day after CO poisoning [calpain 1 (A value): 41.24±5.21 vs. 6.44±1.13, CaMK II (A value): 56.19±5.04 vs. 9.84±1.53, both P < 0.05], and the protein expression of calpain 1 reached the peak at 3 days (A value: 59.34±6.11), the protein expression of CaMK II reached the peak at 1 day (A value: 56.19±5.04). Compared with CO group, the cognitive function was significantly improved in NBP group in the late stage of poisoning [7-30 days, escape latency (s): 40.3±1.9 vs. 49.1±3.1 at 7 days, 30.1±2.9 vs. 39.4±3.1 at 30 days; times of the platform crossing (times): 2.8±1.0 vs. 1.0±0.9 at 14 days, 3.2±0.8 vs. 1.0±0.9 at 30 days, all P < 0.05]; the degree of injury of hippocampal neuron was relatively slight; the protein expression of calpain 1 in brain tissue was significantly decreased from 3 days after CO poisoning (A value: 39.63±3.03 vs. 59.34±6.11, P < 0.05), and the protein expression of CaMK II was significantly decreased from 1 day after CO poisoning (A value: 42.22±3.84 vs. 56.19±5.04, P < 0.05). Immunofluorescence double staining suggested that calpain 1 and CaMK II protein could not only coexist in the same cell, but also could be expressed separately in different cells. Linear regression analysis showed that the expression of calpain 1 and CaMK II was positively correlated (R 2 = 0.852, P = 0.002). CONCLUSIONS: NBP treatment could maintain ultrastructure integrity of hippocampus, balance the expression levels of calpain 1 and CaMK II proteins, and significantly improve cognitive impairment induced by CO poisoning, thus play a protective role against hippocampus damage in rats with acute severe CO poisoning.

Sulphoraphane Improves Neuronal Mitochondrial Function in Brain Tissue in Acute Carbon Monoxide Poisoning Rats.

Carbon monoxide (CO) poisoning is one of the leading causes of toxicity-related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of this study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulphoraphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO. We found that CO poisoning could induce advanced cognitive dysfunction, while the mitochondrial ultrastructure of neurons in rats of the CO poisoning group was seriously damaged and mitochondrial membrane potential (ΔΨm) was accordingly reduced by transmission electron microscopy (TEM) and JC-1 fluorescent probe assay. CO poisoning could also increase the expressions of both nuclear factor erythroid 2-related factor 2 (Nrf-2) and thioredoxin-1 (Trx-1) proteins and their mRNA in brain tissue with immunohistochemistry and quantitative PCR (qPCR) techniques. Early administration of either middle-dose or high-dose SFP could efficiently improve mitochondrial structure and function and enhance the antioxidative stress ability, thus exerting a positive effect against brain damage induced by acute CO poisoning.

N-Butylphthalide Alleviates Blood-Brain Barrier Impairment in Rats Exposed to Carbon Monoxide.

Carbon monoxide (CO) poisoning is one of the most important health concerns and may result in neuropathologic changes and neurologic sequelae. However, few studies have addressed the correlation between CO poisoning and blood-brain barrier (BBB) impairment. In this study, we investigated the effects of N-butylphthalide (NBP) on the expressions of zonula occludens-1 (ZO-1), claudin-5 and aquaporin-4 (AQP-4) proteins in a CO poisoning rat model. The results indicated that the brain water content was obviously increased, and the tight junctions between endothelial cells were disrupted, resulting in significant cerebral edema and BBB dysfunction in a rat model of CO poisoning. Meanwhile, the ultrastructure of endothelial cells and pericytes was seriously damaged, and the expressions of ZO-1 and claudin-5 were decreased at an early stage (<7 days). NBP treatment could efficiently maintain the ultrastructural and functional integrity of BBB, alleviate cerebral edema. Besides, NBP could also markedly increase the levels of both ZO-1 and claudin-5 proteins compared with those in rats exposed to CO (P < 0.05), whereas NBP had no apparent regulatory effect on AQP-4 expression. Taken together, this study highlights the importance of ZO-1 and claudin-5 proteins in maintaining BBB ultrastructure and function after CO poisoning. NBP, as a novel treatment approach, may effectively inhibit the down-regulation of ZO-1 and claudin-5 proteins (but not AQP-4), thereby preserving the barrier function and reducing cerebral edema after CO poisoning.