Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity

The goal of this investigation was to determine whether exposure to hyperbaric oxygen (HBO(2)) would ameliorate biochemical and functional brain abnormalities in an animal model of carbon monoxide (CO) poisoning. In this model, CO-mediated oxidative stress causes chemical alterations in myelin basic protein (MBP), which initiates an adaptive immunological response that leads to a functional deficit. CO-exposed rats do not show improvements in task performance in a radial maze. We found that HBO(2) given after CO poisoning will prevent this deficit, but not eliminate all of the CO-mediated biochemical alterations in MBP. MBP from HBO(2) treated CO-exposed rats is recognized normally by a battery of antibodies, but exhibits an abnormal charge pattern. Lymphocytes from HBO(2)-treated and control rats do not become activated when incubated with MBP, immunohistological evidence of microglial activation is not apparent, and functional deficits did not occur, unlike untreated CO-exposed rats. The results indicate that HBO(2) prevents immune-mediated delayed neurological dysfunction following CO poisoning.     

Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat

Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver–Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning.     

Neuronal nitric oxide synthase and N-methyl-D-aspartate neurons in experimental carbon monoxide poisoning

We measured changes in nitric oxide (NO) concentration in the cerebral cortex during experimental carbon monoxide (CO) poisoning and assessed the role for N-methyl-d-aspartate receptors (NMDARs), a glutamate receptor subtype, with progression of CO-mediated oxidative stress. Using microelectrodes, NO concentration was found to nearly double to 280 nM due to CO exposure, and elevations in cerebral blood flow, monitored as laser Doppler flow (LDF), were found to loosely correlate with NO concentration. Neuronal nitric oxide synthase (nNOS) activity was the cause of the NO elevation based on the effects of specific NOS inhibitors and observations in nNOS knockout mice. Activation of nNOS was inhibited by the NMDARs inhibitor, MK 801, and by the calcium channel blocker, nimodipine, thus demonstrating a link to excitatory amino acids. Cortical cyclic GMP concentration was increased due to CO poisoning and shown to be related to NO, versus CO, mediated guanylate cyclase activation. Elevations of NO were inhibited when rats were infused with superoxide dismutase and in rats depleted of platelets or neutrophils. When injected with MK 801 or 7-nitroindazole, a selective nNOS inhibitor, rats did not exhibit CO-mediated nitrotyrosine formation, myeloperoxidase (MPO) elevation (indicative of neutrophil sequestration), or impaired learning. Similarly, whereas CO-poisoned wild-type mice exhibited elevations in nitrotyrosine and myeloperoxidase, these changes did not occur in nNOS knockout mice. We conclude that CO exposure initiates perivascular processes including oxidative stress that triggers activation of NMDA neuronal nNOS, and these events are necessary for the progression of CO-mediated neuropathology.     

铁离子沉积在急性CO中毒迟发性脑病白质脱髓鞘中的作用

摘要：目的　研究铁离子沉积在急性一氧化碳（CO）中毒迟发性脑病（DEACMP）大鼠脑白质脱髓鞘中的作用。方法　将经Morris水迷宫实验筛选后的SD大鼠随机分成空气对照组（AC组）、CO中毒组（CO组）、去铁胺（DFO）+CO中毒组（DC组）,各组内再分为1、3、7、14、21 d亚组。CO组和DC组采用腹腔注射CO气体法制备DEACMP模型,DC组大鼠于造模前1 h腹腔注射去铁胺100 mg/kg,造模后每天注射1次,AC组和CO组腹腔注射等量生理盐水。采用Morris水迷宫、HE染色观察大鼠染毒前后行为学改变和神经元细胞病理变化;普鲁士蓝染色检测铁离子表达;Western blot检测铁蛋白（Fn）、髓鞘碱性蛋白（MBP）的表达;免疫组化染色检测2',3'-环核苷酸磷酸二酯酶（CNPase）表达;免疫荧光染色检测MBP蛋白表达。结果　染毒14 d后,CO组、DC组逃避潜伏期较AC组延长,DC组逃避潜伏期较CO组缩短,CO组穿越平台次数较AC组及DC组明显减少（P＜0.05）。CO组于染毒14 d细胞变性、坏死明显;DC组细胞变性、坏死介于AC、CO组之间。CO组铁离子表达于14 d达峰值（P＜0.05）,与CO组比较,DC组铁离子、Fn表达减少,染毒3 d后DC组MBP表达增加,14 d和21 d时CNPase表达增多（P＜0.05）。DC组较CO组髓鞘排列较密集,MBP表达增加。结论　急性CO中毒后,过量沉积的铁离子可能通过减少CNPase和MBP的表达,损伤少突胶质细胞,导致大鼠脑白质进行性脱髓鞘,从而发生迟发性认知功能障碍。     

G‐CSF administration attenuates brain injury in rats following carbon monoxide poisoning via different mechanisms

Acute severe carbon monoxide (CO) poisoning induces hypoxia that leads to cardiovascular and nervous systems disturbances. Different complex mechanisms lead to CO neurotoxicity including lipid peroxidation, inflammatory and immune‐mediated reactions, myelin degeneration and finally neuronal apoptosis and necrosis. Granulocyte colony‐stimulating factor (G‐CSF) is considered to be a novel neuroprotective agent. In this study, we evaluated the efficacy of G‐CSF therapy on CO neurotoxicity in rats with acute CO poisoning. Rats were exposed to 3000 ppm CO in air (0.3%) for 1 h, and then different doses (50,100, and 150 µg/kg) of G‐CSF or normal saline were administrated intraperitoneally. Water content of brain as an indicator for total edema and blood brain barrier integrity (Evans blue extravasation) were evaluated. Malondialydehyde was determined in order to evaluate the effect of G‐CSF on CO‐induced lipid peroxidation in brain tissues. Also, the effect of G‐CSF on myeloperoxidase activity in the brain tissue was evaluated. The effect of G‐CSF administration on induced apoptosis in the brain was measured using TUNEL method. To evaluate the level of MBP, STAT3 and pSTAT3 and HO‐1 proteins and the effect of G‐CSF on these proteins Western blotting was carried out. G‐CSF reduced water content of the edematous poisoned brains (100 µg/kg) and BBB permeability (100 and 150 µg/kg) (P < 0.05). G‐CSF (150 µg/kg) reduced the MDA level in the brain tissues (P < 0.05 as compared to CO poisoned animals). G‐CSF did not decrease the MPO activity after CO poisoning in any doses. G‐CSF significantly reduced the number of apoptotic neurons and Caspase 3 protein levels in the brain. Western blotting results showed that G‐CSF treatment enhanced expression of HO‐1 and MBP, STAT3 and pSTAT3 proteins in the brain tissues. Based on our results, a single dose of G‐CSF immediately after CO poisoning significantly attenuates CO neurotoxicity via different mechanisms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 37–47, 2017.     

依达拉奉缓解大鼠急性一氧化碳中毒所致脑损伤机制探讨

目的：观察依达拉奉对大鼠急性一氧化碳( CO)中毒所致脑损伤的疗效,并探讨其可能的作用机制。方法取健康成年SD大鼠60只,随机分为生理盐水组( NS组)10只、CO中毒对照组( CO组)30只、CO中毒+依达拉奉实验组(实验组)20只。在实验第3、7、14 d后处死大鼠,用蛋白质印迹技术比较各时间点3组中髓鞘碱性蛋白质( myelin basic protein,MBP)的含量,以RT-PCR技术对3组中Bcl-2 mRNA和Bax mRNA的表达水平,以蛋白质印迹技术检测各时间3组Keap-1及Nrf-2的表达水平。结果实验3 d时3组MBP含量差异无统计学意义(P>0．05);在7、14 d时CO组和实验组较NS组明显下降(P<0．05),而实验组比CO组表达量增多(P<0．05);在3、7、14 d时CO组Bcl-2 mRNA表达水平均显著高于NS组( P<0．05),实验组显著高于NS组和CO组( P<0．05);CO组和实验组Bax mRNA表达水平在3、7、14 d均显著高于NS组(P<0．05),实验组Bax mRNA表达水平在3 d与CO组的表达差异无统计学意义(P<0．05),而在7、14 d显著低于CO组(P<0．05);在3、7、14 d时Keap1、Nrf-2含量CO组及实验组比NS组明显增多(P<0．01),实验组比CO组明显增多(P<0．01)。结论依达拉奉可减轻急性CO中毒所致的脑损伤程度,其作用机制可能是通过Keap-1/Nrf-2的途径而实现。     

Methyl group balance in brain and liver: Role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure

Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain.     

Acute CO Poisoning is Associated with Impaired Fibrinolysis and Increased Thrombin Generation

Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in many countries. In ex vivo studies, CO released from carbon monoxide‐releasing molecules has been shown to attenuate fibrinolysis via increased alpha‐2‐antiplasmin activity. Hypofibrinolysis is associated with coronary ischaemia, which is also commonly observed in CO poisoning. We examined fibrin clot properties in acutely poisoned CO patients. Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 48 patients and controls matched for age and sex. CO‐poisoned patients had 11.6% longer clot lysis time than the controls (p < 0.0001). No intergroup differences in clot permeability or turbidimetric variables were observed. Plasma tissue‐type plasminogen antigen (tPA), plasminogen activator inhibitor‐1 (PAI‐1) antigen and activity and F1.2 prothrombin fragments were higher in the patients than in the controls (all p < 0.0001). Plasma tPA activity was lower in the CO‐poisoned group. Multiple linear regression showed that a thrombin generation marker, F1.2, is the strongest predictor of clot lysis time, followed by PAI‐1 activity and carboxyhaemoglobin levels. In conclusion, this report is the first to demonstrate that acute CO poisoning in human beings is linked to increased thrombin generation and impaired fibrinolysis, which might contribute to ischaemic complications.     

Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain

Carbon monoxide (CO) toxicity is the result of a combination of tissue hypoxia and direct CO-mediated damage at a cellular level, since not all the signs and symptoms presented can be explained only by the formation of carboxyhaemoglobin. Mitochondria, specially the electron transport chain, seem to be the target for CO at a subcellular level. However, the direct effect of CO in individual complexes of the human mitochondrial respiratory chain has not been completely elucidated. We here studied the in vitro effect of CO on individual complexes of the mitochondrial respiratory chain of human mitochondria. We obtained muscle tissue from 10 healthy people who underwent orthopaedic surgery for hip replacement. Isolated mitochondria were incubated for 5 min. under CO concentrations of 50, 100 and 500 ppm. Afterwards, enzymatic activities of individual complexes of the mitochondrial respiratory chain were assessed in vitro and compared with those obtained in basal (synthetic air without CO) conditions. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) activity showed a decrease from 836+/-439 nmol/min./mg of mitochondrial protein after air incubation to 670+/-401, 483+/-182, and 379+/-131 nmol/min./mg after 50, 100 and 500 ppm of CO incubation, respectively (20%, 42% and 55% decrease in cytochrome c oxidase activity). This gradual decrease in cytochrome c oxidase was found to be statistically significant (P<0.001). Other complex activities showed no any significant variation. Carbon monoxide is toxic for mitochondria in man, altering the mitochondrial respiratory chain at the cytochrome c oxidase level. This inhibition in cytochrome c oxidase may play a role in the development of the symptoms observed in acute CO poisoning, and in some diseases related to smoking.     

Immunological Changes Produced in Rats by Prenatal Exposure to Carbon Monoxide

Abstract: Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (CO) (75 and 150 p.p.m.) from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decreased in 15 and 21 day old male rats exposed to CO (150 p.p.m.) during pregnancy. Moreover, splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of CO. Prenatal CO (150 p.p.m.) significantly decreased splenic macrophage O₂^- release in both 15 and 21 day old pups. CO-induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to relatively mild concentrations of CO induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage function.     

Elevated Carboxyhaemoglobin Concentrations by Pulse CO‐Oximetry is Associated with Severe Aluminium Phosphide Poisoning

In pulse CO‐oximetry of aluminium phosphide (ALP)‐poisoned patients, we discovered that carboxyhaemoglobin (CO‐Hb) level was elevated. We aimed to determine whether a higher CO level was detected in patients with severe ALP poisoning and if this could be used as a prognostic factor in these patients. In a prospective case – control study, 96 suspected cases of ALP poisoning were evaluated. In the ALP‐poisoned group, demographic characteristics, gastric and exhalation silver nitrate test results, average CO‐Hb saturation, methaemoglobin saturation, and blood pressure and blood gas analysis until death/discharge were recorded. Severely poisoned patients were defined as those with systolic blood pressure ≤80 mmHg, pH ≤7.2, or HCO₃ ≤15 meq/L or those who died, while patients with minor poisoning were those without any of these signs/symptoms. A control group (37 patients) was taken from other medically ill patients to detect probable effects of hypotension and metabolic acidosis on CO‐Hb and methaemoglobin saturations. Of 96 patients, 27 died and 37 fulfilled the criteria for severe poisoning. All patients with carbon monoxide saturation >18% met the criteria to be included in the severe poisoning group and all with a SpCO >25% died. Concerning all significant variables in univariate analysis of severe ALP toxicity, the only significant variable which could independently predict death was carbon monoxide saturation. Due to high mortality rate and need for intensive care support, early prediction of outcome is vital for choosing an appropriate setting (ICU or ordinary ward). CO‐oximetry is a good diagnostic and prognostic factor in patients with ALP poisoning even before any clinical evidence of toxicity will develop.     

Carbon monoxide as a novel central pyrogenic mediator

Carbon monoxide (CO) are produced by heme oxygenase (HO), and HO was detected in hypothalamus. However, the roles of CO produced in hypothalamus was not fully elucidated. So, we tested the effects of CO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. CO-saturated aCSF (4 microl, i.c.v.) and hemin (10 microg, i.c.v.) elicited marked febrile response. Pretreatment with indomethacin completely inhibited CO- and hemin-induced fever. Zinc protoporphyrin-IX (10 microg, i.c.v.) or ODQ (50 microg, i.c.v.) partially reduced hemin-induced febrile response. Dibutyryl-cGMP (100 microg, i.c.v.) produced profound febrile response and this febrile response was attenuated by indomethacin. These results indicate that endogenous CO may have a role as a pyrogenic mediator in CNS and CO-mediated pyresis is dependent on prostaglandin production and partially on activation of soluble guanylate cyclase.     

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.     

Positive inotropic effects of carbon monoxide-releasing molecules (CO-RMs) in the isolated perfused rat heart

BACKGROUND AND PURPOSE: Carbon monoxide (CO) generated by the enzyme haeme oxygenase-1 (HO-1) during the breakdown of haeme is known to mediate a number of biological effects. Here, we investigated whether CO liberated from two water soluble carbon monoxide-releasing molecules (CO-RMs) exerts inotropic effects on the myocardium. EXPERIMENTAL APPROACH: Rat isolated hearts perfused either at constant flow or constant pressure were used to test the effect of CO-RMs. KEY RESULTS: CORM-3, a fast CO releaser, produced a direct positive inotropic effect when cumulative doses (3, 10 and 30 microg min(-1)) or a single dose (5 microM) were infused at either constant coronary pressure (CCP) or constant coronary flow (CCF). The inotropic effect mediated by CORM-3 was abolished by blockade of soluble guanylate cyclase or Na(+)/H(+) exchanger, but not by inhibitors of L-type Ca(2+) channels and protein kinase C. CORM-3 also caused a slight reduction in heart rate but did not alter coronary flow. In contrast, the slow CO releaser CORM-A1 produced significant coronary vasodilatation when given at the highest concentration (30 mug min(-1)) but exerted no effect on myocardial contractility or heart rate. CONCLUSION AND IMPLICATIONS: A rapid CO release from CORM-3 exerts a direct positive inotropic effect on rat isolated perfused hearts, whereas CO slowly released by CORM-A1 had no effect on myocardial contractility but caused significant coronary vasodilatation. Both cGMP and Na(+)/H(+) exchange appear to be involved in this effect but further work is needed to determine the relative contribution of each pathway in CO-mediated inotropic effect.     

依达拉奉对脑梗死大鼠神经髓鞘再生、认知功能及VEGF/Notch1信号通路的影响

目的 探讨依达拉奉对脑梗死大鼠神经髓鞘再生、认知功能及血管内皮生长因子（VEGF）/跨膜体受体蛋白（Notch1）信号通路的影响。方法 50只大鼠按照随机数字表法分为对照组、模型组、阿司匹林组和依达拉奉1.5、3 mg/kg组，每组10只。除对照组外，其余组大鼠均建立大脑中动脉梗死模型，依达拉奉1.5、3mg/kg组分别尾iv依达拉奉注射液，阿司匹林组注射4 mg/kg阿司匹林溶液。穿梭箱联合水迷宫实验观察各组大鼠认知功能；ELISA法检测各组大鼠血清髓鞘碱性蛋白（MBP）含量；Pal-Weigert染色观察各组大鼠神经髓鞘形态；TTC染色测定各组大鼠脑梗死体积；免疫印迹法检测各组大鼠VEGF/Notch1水平。结果 与模型组比较，依达拉奉各剂量组能够主动逃避次数增加，被电次数、学习和记忆潜伏时间减少（P＜0.05）；与模型组比较，依达拉奉各剂量组血清MBP含量、梗死体积、Notch1水平下降，VEGF水平升高（P＜0.05）。模型组髓鞘崩解、破坏、脱失严重，髓鞘稀疏，部分区域有髓鞘断裂缺失，染色变浅；依达拉奉各剂量组及阿司匹林组髓鞘形态改善。结论 依达拉奉可促进VEGF活性，抑制炎症反应，调控Notch1信号通路，降低MBP蛋白表达，促进神经髓鞘再生，提升认知功能。     

Nature's marvels endowed in gaseous molecules I: Carbon monoxide and its physiological and therapeutic roles

Nature has endowed gaseous molecules such as O₂, CO₂, CO, NO, H₂S, and N₂ with critical and diverse roles in sustaining life, from supplying energy needed to power life and building blocks for life''s physical structure to mediating and coordinating cellular functions. In this article, we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of molecules. The past twenty years have seen much progress in understanding CO''s mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy administration. One remarkable trait of CO is its pleiotropic effects that have few parallels, except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen sulfide. This review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications.KEY WORDS: Carbon monoxide, Gasotransmitter, Gaseous signaling molecule, CO releasing molecule, Organic CO prodrug, Homeostasis, Pleiotropic effect, Yin and Yang     

Single Versus Multiple Hyperbaric Sessions for Carbon Monoxide Poisoning in a Murine Model

Hyperbaric oxygen (HBO) has been advocated for treatment of acute carbon monoxide (CO) poisoning. There exists considerable debate as to whether HBO prevents delayed neurologic sequelae (DNS) due to CO poisoning. Additionally, existing data in the literature supporting HBO efficacy do not identify an optimal number of HBO treatments. We sought to determine in a mouse model whether there is a difference between one versus multiple HBO sessions for the prevention of DNS. Fifty mice were randomized into five groups of ten mice each: (1) control, receiving no CO exposure or treatment; (2) CO poisoned, receiving no treatment (CO group); (3) CO poisoned, receiving normobaric oxygen for 58 min following the end of exposure (CO + NBO group); (4) CO poisoned, followed by one session of HBO(CO + HBO1); and (5) CO poisoned, followed by three HBO treatment sessions, one every 6 h (CO + HBO3). Prior to poisoning, all animals were trained in step-down latency (SDL) and step-up latency (SUL) tasks. One week after exposure and treatment, all five groups were retested to evaluate the retention of this training. There was no difference detected among groups in SDL (p = 0.67 among all groups) when evaluated using a Kruskal-Wallis test. There was a significant difference among groups in SUL (p = 0.027 among all groups) when evaluated using a Kruskal-Wallis test. When individual groups were compared using a Wilcoxon signed-rank test with Bonferroni correction, there were no statistically significant differences in either SDL or SUL. There was no difference between groups treated with either one or three HBO sessions. One possibility to explain this might be that HBO sessions administered some time after a CO exposure may enhance the lipid peroxidation cascade and worsen neurologic outcomes; alternatively, HBO may simply impart no benefit when compared to NBO.     

Effect of lindane on the myelination process in the rat

After lindane administration at several doses, brain myelin fractions of litters of male and female Wistar rats show a significant diminution of CNP (2′,3′-cyclic nucleotide 3′-phosphodiestera activity. Furthermore, the immunohistochemical study of brains by means of a MBP (myelin basic protein) specific antibody reveals myelin deficits in some brain regions after lindane treatment. This loss of myelin protein is dose dependent. The deficit in myelin cannot be attributed to undernourishment of lindane-administered rats. This work shows the vulnerability of the developing central nervous system (CNS) to lindane and the correlation between a decrease in the CNPase activity and a deficit of MBP during the period of study of these animals.     

急性CO中毒患者血清S100B、NSE、MBP的动态改变及其意义

目的探讨急性一氧化碳中毒患者血清S100B、神经元特异性烯醇化酶（NSE）、髓鞘碱性蛋白（MBP）的动态改变及其与患者的病情、预后的关系。方法检测30名健康体检者和185例一氧化碳中毒患者入院时SIOOB、NSE、MBP水平,并对其中60例中重型住院病人第2、3天这些指标进行检测,分析其与患者预后的关系。结果入院时,中重型一氧化碳中毒患者血清S100B、NSE水平明显高于对照组和轻型一氧化碳中毒患者;中重型患者血清MBP水平高于轻型,轻型高于对照组。对中重型一氧化碳中毒患者,死亡患者第2天SIOOB、NSE水平明显高于人院时水平,第3天与第2天相比无统计学差异;而MBP水平在3天中无明显改变（P〉0．05）;存活患者中,SIOOB、NSE、MBP3天无明显改变。结论一氧化碳中毒患者入院时MBP水平与患者病情密切相关,而动态检测NSE、SIOOB水平能有效地判断对患者预后。     

Effects of early postnatal exposure to low concentrations of carbon monoxide on cognitive functions in rats.

Male Wistar rats were exposed to 75 and 150 ppm of carbon monoxide (CO) from day 1 after birth until postnatal day 10 and their cognitive functions were evaluated at 3 and 18 months of age. The results show that early postnatal exposure to CO does not affect the acquisition and reacquisition of an active avoidance task in both adult and aged rats. Conversely, our previous findings indicate that prenatal exposure to CO (75 and 150 ppm), resulting in maternal blood carboxyhaemoglobin concentrations equivalent to those found in human cigarette smokers, induces long-lasting learning and memory deficits. These findings suggest that neurofunctional sequelae of prenatal CO exposure are notably different from those occurring in response to early postnatal exposure and that the vulnerability of the developing brain to prolonged, relatively mild, decrease in oxygen availability induced by CO critically depends on the particular period of developmental exposure.