Carbon Monoxide Encephalopathy Research Articles

Neural precursor cells are decreased in the hippocampus of the delayed carbon monoxide encephalopathy rat model

The pathophysiology of delayed carbon monoxide (CO) encephalopathy remains unclear. In this study, the effects of CO exposure on the dentate gyrus (DG) were investigated in a Wistar rat model by histochemical and molecular methods. Model rats showed significant cognitive impairment in the passive-avoidance test beginning 7 days after CO exposure. Immunohistochemistry showed that compared to the control, the cell number of SRY (sex-determining region Y)-box 2 (SOX2)+/brain lipid binding protein (BLBP)+/glial fibrillary acidic protein (GFAP)+ cells in the DG was significantly less, but the number of SOX2+/GFAP− cells was not, reflecting a decreased number of type 1 and type 2a neural precursor cells. Compared to the control, the numbers of CD11b+ cells and neuron glial antigen 2+ cells were significantly less, but the number of SOX2−/GFAP+ cells was not. Flow cytometry showed that the percent of live microglial cells isolated from the hippocampus in this CO rat model was significantly lower than in controls. Furthermore, mRNA expression of fibroblast growth factor 2 and glial cell-derived neurotrophic factor, which are neurogenic factors, was significantly decreased in that area. We conclude that, in this rat model, there is an association between delayed cognitive impairment with dysregulated adult hippocampal neurogenesis and glial changes in delayed CO encephalopathy.

The nicotinic cholinergic system is affected in rats with delayed carbon monoxide encephalopathy

Delayed carbon monoxide (CO) encephalopathy may occur following recovery from acute CO poisoning. However, the mechanism of delayed neuronal injury remains unknown. The nicotinic acetylcholine receptors (nAChRs) have been suggested to play a role in cognitive status in neurodegenerative diseases, including Alzheimer's disease. Therefore, in the current study, we investigated the effect of delayed neuronal CO poisoning on gene expression of nAChRs in the hippocampus of Wistar rats. Behavioral effects (measured by the passive-avoidance test) and histological analyses (hematoxylin–eosin-stained hippocampal cell counts and cell death observations) were also investigated, 21 days after CO exposure for 1h (1000ppm for 40min+3000ppm for 20min). Our findings show cognitive impairment and hippocampal cell death, suggesting our rat model is suitable for studying delayed CO encephalopathy. Expression of nAChR (Chrna3, Chrna4, Chnra7, and Chrnb2) mRNA was assessed using quantitative real-time polymerase chain reaction. Hippocampal Chrna3 expression was significantly decreased, and cerebellar Chrna7 expression significantly increased, in the delayed CO encephalopathy rat model. Thus, the nicotinic cholinergic system may be affected in delayed CO encephalopathy.

Can MRI Findings in Carbon Monoxide Poisoning Predict Carbon Monoxide Encephalopathy?

Carbon monoxide (CO) is a tasteless, odorless, non-irritating, but highly toxic gas. CO encephalopathy (COE) may occur from 3 days up to 240 days after acute CO exposure, and has poor prognosis. Brain magnetic resonance imaging (MRI) changes after CO poisoning are variable and well reflect the neuropathological lesions. The areas of the brain that are the most sensitive to the effects of CO poisoning include the globus pallidus and other basal ganglia, the white matter, and the cerebral cortex. This study was conducted to investigate the role of MRI in predicting COE in patients with CO poisoning.

Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon monoxide toxicity

We investigated the feasibility and efficacy of hydrogen-rich saline therapy on delayed neurologic sequelae in a rat model of severe acute carbon monoxide (CO) poisoning. Controlled animal study. University research laboratory for Diving Medicine. Sprague-Dawley rats weighing 250 ± 20 g. The rats were exposed to 1000 ppm CO in air for 40 min and then to 3000 ppm for another 20 min until they lost consciousness. Rats were intraperitoneal injected with hydrogen-rich saline or normal saline (10 mL/kg) for six times after resuscitation at 0, 12, 24, 36, 48, and 60 hrs, respectively. The rats without CO poisoning were used as normal controls. Brain tissue inflammation, cell death, and cognitive dysfunction were observed at one week after CO poisoning. Hydrogen-rich saline treatment significantly reduced the level of degraded myelin basic protein, decreased the expression of ionized calcium-binding adapter molecule 1, Iba1, a microglial marker, reduced DNA oxidation, and suppressed proinflammatory cytokine interleukin-1β, interleukin-6, and tumor necrosis factor-α in the cortex and hippocampal tissues when compared with those in normal saline-treated rats. These histologic and biological improvements were accompanied with an improvement in the Morris water maze test. This observation demonstrated that hydrogen-rich saline peritoneal injection improves histologic and functional assessment in a rat model of CO encephalopathy. Hydrogen saline has potentials as a novel and alternative therapy for severely CO-poisoned patients with delayed neurologic sequelae. The therapeutic effects of hydrogen-rich saline may be related to antioxidant and anti-inflammatory actions.

Longitudinal study of carbon monoxide intoxication by diffusion tensor imaging with neurospsychiatric correlation

White matter damage is common after carbon monoxide (CO) intoxication, but in vivo follow-up studies about the mechanism of white matter damage are not possible in pathology series. Diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) can quantify diffusion parameters and volumetric changes in white matter that can be correlated with neuropsychological performances in longitudinal studies. We examined 9 patients with CO intoxication using DTI, VBM and neuropsychologic tests at an average of 3 and 10 months after CO exposure. We used data from 18 age- and sex-matched controls for comparison. We found that cognitive recovery at 10 months after CO intoxication was not significant, although it was after 3 months. The neuropsychologic tests correlated better for the fibre tract of the semicentrum ovale and not the periventricular fibres. Diffusion measures suggest increases in fractional anisotropy, mean diffusivity and axial eigenvalues over time, while increases in radial eigenvalue were evident at 3 months compared with controls. Periventricular white matter atrophy was observed 10 months after CO intoxication. Our study included few cases, and the interpretation of the putative changes on neuroimaging findings cannot be confirmed by histology. Our study showed that the evolution of white matter injury in CO encephalopathy occurred over time. Cognitive recovery was not evident in the follow-up period because of white matter injuries.

Ziprasidone in the treatment of delayed carbon monoxide encephalopathy

Delayed carbon monoxide (CO) encephalopathy is a serious complication of acute CO poisoning. We present a case of successful treatment of ziprasidone, a newer atypical antipsychotic, in delayed CO encephalopathy. A 52-year-old depressed woman suffered acute CO intoxication after an attempt of suicide by burning charcoal. She was initially treated with hyperbaric oxygen (HBO) therapy for the acute intoxication. One week later, the patient developed neuropsychiatric symptoms including parkinsonism, tardive dyskinesia (TD), cognitive deterioration, urinary incontinence, gait disturbance, mutism, disorientation to time, place and person, and disorganized as well as disturbing behavior. During her psychiatric hospitalization, the patient had been treated with daily HBO therapy, bromocriptine (2.5 mg/day), the conventional antipsychotic sulpiride (600 mg/day), and atypical antipsychotics such as risperidone (5 mg/day) and quetiapine (400 mg/day). However, her delayed neuropsychiatric sequelae of CO intoxication persisted despite of these treatments. It was until she had been treated with ziprasidone (80 mg/day) for 10 days that her mental condition was improved. With ziprasidone therapy, the patient obtained substantial improvement in her neuropsychiatric symptoms, cognitive function, and daily activities. Our case indicates that ziprasidone can be used effectively in the treatment of delayed CO encephalopathy.

Cognitive recovery after delayed carbon monoxide encephalopathy

We report on a patient with delayed carbon monoxide encephalopathy who presented with severe cognitive impairment associated with MRI findings of extensive demyelination of the cerebral white matter after a silent period of three weeks from acute intoxication. Despite the severe signs of structural and functional cerebral impairment in the sub-acute stage, the clinical course was favorable but for residual mild dysfunction of the frontal lobes.

Parkinsonism after Carbon Monoxide Poisoning

Of 242 patients with carbon monoxide (CO) poisoning examined between 1986 and 1996, parkinsonism was diagnosed in 23 (9.5%). There were 11 men and 12 women. The age at onset ranged from 16 to 69 (mean 45.8) years, with the peak incidence during the 6th decade. The latency before the appearance of parkinsonism varied from 2 to 26 (median 4) weeks, but parkinsonism developed within 1 month after an acute insult in the majority of the patients. All showed encephalopathy with mildly to severely impaired cognitive functions during or immediately after delayed CO sequelae. The common symptoms were gait disturbance, impaired mentality, urinary incontinence, and mutism. The most frequent signs were short-step gait, hypokinesia, masked face, increased muscle tone (rigidity), glabella sign, grasp reflex, and retropulsion. Intentional tremor was occasionally found, but resting tremor could not be seen. There was no correlation between the neuroimaging findings and the development of parkinsonism. Levodopa and anticholinergic drugs were not effective. Of 16 patients followed up for 1 year, 13 (81.3%) recovered spontaneously within 6 months. In conclusion, parkinsonism after CO poisoning is not rare and usually appears as a part of delayed CO encephalopathy. Any drug is not effective, but the prognosis is good.

Delayed Movement Disorders after Carbon Monoxide Poisoning

Of 242 patients with carbon monoxide (CO) poisoning examined between 1986 and 1996, delayed movement disorders were diagnosed in 32 (13.2%). There were 15 men and 17 women. Ages at insult ranged from 9 to 69 years (mean 45.3 years). Of the 32 patients with delayed movement disorders, 23 (71.9%) had parkinsonism, 5 dystonia, 3 chorea and 1 myoclonus. All were associated with delayed CO encephalopathy. The median latency between CO poisoning and the onset of movement disorders was 4 weeks for parkinsonism, 51 weeks for dystonia, 4 weeks for chorea and 8 weeks for myoclonus. The latency of dystonia onset after CO poisoning was longer than that of other types of movement disorders. The CT findings in delayed movement disorders after CO poisoning were variable, and there was no correlation between the sites of imaging and the development of movement disorders. Abnormal dyskinesias disappeared within 8 weeks, and patients recovered from parkinsonism within 6 months. In conclusion, delayed movement disorders after CO poisoning are not rare, and usually appear as a part of delayed CO encephalopathy. The prognosis is good.

Delayed-onset progressive movement disorders after static brain lesions.

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Neuropsychological testing, carbon monoxide encephalopathy and hyperbaric oxygen therapy

Neuropsychological testing, carbon monoxide encephalopathy and hyperbaric oxygen therapy

Neuropsychological testing, carbon monoxide encephalopathy and hyperbaric oxygen therapy

Neuropsychological testing, carbon monoxide encephalopathy and hyperbaric oxygen therapy

Comparative study on pathogenesis of selective cerebral lesions in carbon monoxide poisoning and nitrogen hypoxia in cats.

Since in a previous study hypoxia and subsequent hypotension were considered to be essential for the pathogenesis of carbon monoxide encephalopathy (CO-encephalopathy), experiments were conducted to see whether a combination of nitrogen hypoxia and subsequent systemic hypotension of similar degree and duration as in the previous experimental CO poisoning could induce the same lesion in the CNS of cats. The partial pressure of blood oxygen was reduced to less then 26 mm Hg by increasing the concentration of nitrogen in N2/O2 gas to be inhaled in 1.5h and then the aortic blood pressure (BP) was reduced to 60-80 mm Hg by blood depletion and ganglion-blockage for 1h. In 11 of the 15 cats, lesions were produced in the CNS which were similar by light and electron microscopy to those in CO-encephalopathy. In control groups which were treated by hypoxemia only, hypotension only or a combination CO2-gas inhalation and hypotension without hypoxemia, such lesions were not found in the cerebral white matter. Considering the pathogenesis of lesions in the cerebral white matter in both nitrogen hypoxia and CO-poisoning, two factors i.e., hypoxemia and subsequent systemic hypotension, are common and essential. Further, the enormous vasodilatation in the cerebral white matter induced by hypoxemia and subsequent drop in BP seem to cause a more severe circulatory disturbance in the cerebral white matter than in the cortex.

The pathogenesis of carbon monoxide encephalopathy in the acute phase?Physiological and morphological correlation

Experimental studies were performed to elucidate the significance of various physiological factors contributing to the pathogenesis of carbon monoxide (CO) encephalopathy, such as systemic blood pressure (BP), common carotid artery blood flow (CF), local blood flow (LBF) of the brain and blood gas including pH, and to analyse the morphological character of the cerebral white matter lesions in the acute phases with light and electron microscopes; 14 adult cats were exposed to 0.3% CO/air gas under respiratory control for 1 h and 17 min to 2 h and 50 min and killed 1.5 h to 3 weeks later.