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Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS).

ABSTRACT: Delayed neurologic sequelae (DNS) are recurrent-transient neuropsychiatric consequences of carbon monoxide (CO) intoxication. Pathologically DNS features damages to the brain white matter. Here we test a hypothesis that direct cytotoxicity of CO to oligodendrocytes plays a role in the development of DNS. In an in vitro model of CO poisoning with the carbon monoxide releasing molecule-2 (CORM-2) as a CO donor, we show that CORM-2 at concentrations higher than 200 µM significantly inhibited viability and caused significant death of PC12 cells. Similar minimum toxicity concentration was observed on primary brain cells including neurons, astrocytes, and microglia. Interestingly, oligodendrocytes showed cytotoxicity to CORM-2 at a much lower concentration (100 µM). We further found that CORM-2 at 100 µM inhibited proteolipid protein (PLP) production and reduced myelin coverage on axons in an in vitro model of myelination. Our results show that direct cytotoxicity is a mechanism of CO poisoning and DNS may result from a high susceptibility of oligodendrocytes to CO poisoning.

SUBMITTER: Tian X

PROVIDER: S-EPMC7438756 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS).

Tian Xiaofei X Guan Teng T Guo Ying Y Zhang Guohui G Kong Jiming J

Frontiers in psychiatry 20200813

Delayed neurologic sequelae (DNS) are recurrent-transient neuropsychiatric consequences of carbon monoxide (CO) intoxication. Pathologically DNS features damages to the brain white matter. Here we test a hypothesis that direct cytotoxicity of CO to oligodendrocytes plays a role in the development of DNS. In an <i>in vitro</i> model of CO poisoning with the carbon monoxide releasing molecule-2 (CORM-2) as a CO donor, we show that CORM-2 at concentrations higher than 200 µM significantly inhibited ...[more]

PMID: 32903698

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Project description:Importance:Preventing delayed neurological sequelae is a major goal of treating acute carbon monoxide poisoning, but to our knowledge there are no reliable tools for assessing the probability of these sequelae. Objectives:To determine whether acute brain lesions on diffusion-weighted imaging are related to subsequent development of delayed neurological sequelae after acute carbon monoxide poisoning. Design, Setting, and Participants:This registry-based observational study was conducted at a university hospital in Seoul, Korea, between April 1, 2011, and December 31, 2015. Of 700 patients (aged ?18 years) with acute carbon monoxide poisoning, 433 patients (61.9%) who underwent diffusion-weighted imaging at an emergency department were considered for the study. Patients who developed cardiac arrest before diffusion-weighted imaging (n?=?3), had persistent neurological symptoms at discharge (n?=?8), committed suicide soon after discharge (n?=?1), and were lost to follow-up (n?=?34) were excluded. Exposure:The presence of unambiguous, high-signal-intensity, acute brain lesions on diffusion-weighted imaging (b?=?1000 s/mm2). Main Outcomes and Measures:Development of delayed neurological sequelae defined as any neurological symptoms or signs that newly developed within 6 weeks of discharge. Results:Of the 387 included patients (143 women [37.0%]; median age, 42.0 years [interquartile range, 32.0-56.0 years]), acute brain lesions on diffusion-weighted imaging were observed in 104 patients (26.9%). Among these, 77 patients (19.9%) had globus pallidus lesions, 13 (3.4%) had diffuse lesions, and 57 (14.7%) had focal lesions (37 patients [9.6%] had >1 pattern concurrently). Lesions were supratentorial and infratentorial in 101 and 23 patients, respectively. Delayed neurological sequelae occurred in 101 patients (26.1%). Multivariable logistic regression analysis indicated that the presence of acute brain lesions was independently associated with development of delayed neurological sequelae (adjusted odds ratio, 13.93; 95% CI, 7.16-27.11; P?<?.001). The sensitivity and specificity of acute brain lesions to assess the probability of delayed neurological sequelae were 75.2% (95% CI, 66.8%-83.7%) and 90.2% (95% CI, 86.8%-93.7%), respectively. In addition, the positive and negative predictive values were 73.1% (95% CI, 64.6%-81.6%) and 91.2% (95% CI, 87.9%-94.5%), respectively. Conclusions and Relevance:The presence of acute brain lesions was significantly associated with the development of delayed neurological sequelae. Diffusion-weighted imaging during the acute phase of carbon monoxide poisoning may therefore help identify patients at risk of developing these debilitating sequelae.

Dataset Information

Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS).

Publications

Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS).

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