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Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER
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Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER
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Animals , Mice , Clemastine , Hypoxia/complications , Mice, Inbred C57BL , Mice, Transgenic , Myelin Sheath , OligodendrogliaABSTRACT
Se han establecido regulaciones para la exposición ocupacional a cargas físicas del trabajo, y a hipoxia intermitente crónica (HIC). También se ha indicado incorporar los riesgos asociados a HIC a un sistema de gestión de seguridad y salud en el trabajo. Dado que las cargas físicas de trabajo (CFT) en HIC pueden condicionar riesgos de trabajo pesado y fatiga física, se considera oportuno revisar el efecto de la CFT a gran altitud, entre 3000 y 5500 m de altura, sobre el riesgo de trabajo pesado, por lo cual se procede a recopilar estudios de campo de la capacidad aeróbica, mediciones de los signos que permiten evaluar el % de Carga Cardiovascular (%CCV) ocupado a gran altura. El %CCV se calcula mediante las frecuencias cardíacas (FC) de reposo, la máxima y la de trabajo. El monitoreo continuo de la FC y mediciones directas de la capacidad aeróbica máxima muestran que en HIC se modifican las tres FC de %CCV, también se muestra que cuando la FC de trabajo en altitud está por sobre 110 latidos/minuto hay mayor riesgo de fatiga y trabajo pesado. Adicionalmente se encontró que la capacidad aeróbica, VO2máx, medido a nivel del mar se reduce en trabajadores aclimatados a HIC con una reducción del 7% de la FC máxima. Este efecto, entendido como frenación fisiológica protectora, se puede perder durante una desaclimatación a nivel de mar por más de 10 días. En vista de una mayor probabilidad de trabajo pesado en HIC se proponen intervenciones para prevenir, controlar y mitigar riesgos de fatiga, cansancio y trabajo pesado que afecten la salud, conducta segura y productividad. En conclusión, en faenas a gran altitud, la CFT se puede evaluar mediante medición del %CCV basada en registros de la FC de reposo, máxima y de trabajo, en cada cota donde se ejecuta la actividad laboral, porque la hipoxia hipobárica modifica los tres componentes de esa ecuación.
Regulations have been established for the occupational exposition to physical loads from work, and chronic intermittent hypoxia (HIC). Also, it has been indicated to include the associated HIC risks to a security and health management system at work. Since physical workload (CFT) in HIC can condition risks of hard work and physical fatigue, it is considered appropriate to review the CFT effect at high altitude, between 3000 and 5500m of altitude, over the risks of hard work, which is why is proceeding to compile field studies about the aerobic capacity, measures of signs that allows assessing the % of Cardiovascular load (%CCV) used at great altitudes. The % CCV is estimated by cardiac frequencies (FC) at rest, maximum, and from work. The FC continuous monitoring and direct measures of the maximum aerobic capacity displays that the three FC of %CCV are modified in HIC is also displayed that when the work FC in altitude is over 110 heartbeats/minute there is major fatigue and hard work risk. Moreover, it was determined that aerobic capacity, VO2 max, measured at sea level is reduced in acclimated workers to HIC with a 7% reduction of maximum FC. This effect, known as physiological protective restrain, can be lost during a deacclimation at sea level for more than 10 days. At the sight of a greater probability of hard work in HIC, interventions are proposed to prevent, control, and reduce fatigue risks, tiredness, and hard work that affects health, safe-conduct, and productivity. In conclusion, in chores at high altitudes, CFT can be assessed by measuring the %CCV based on date from the FC in rest, maximum and from work, in each height where work activities are performed, because the hypobaric hypoxia modifies the three components of that equation.
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Humans , Occupational Exposure , Workload , Altitude , Hypoxia , Age Factors , Heart RateABSTRACT
After the accident on Apolo1, with 100% oxygen in the cabin, all spaceships now travel with a sea level pressure and 20.9% oxygen. Extravehicular activity requires lowering the pressures. It is complex and time consuming. Permanently reducing the cabin pressure would be a great advantage. A paper by NASA in 2013, proposed for the spaceflight environment: 8 psia / 32% O2 (reducing the sea level pressure (14.7 psi / 20.9% O2), but increasing the fraction of oxygen in order to replicate the sea level PaO2). However, we question this proposal, as it is based on the fear of hypoxia. Our proposal back in 2007 suggested that space travel should take place in a hypobaric environment of 9.5 psi / 20.9% O2 (like in the city of La Paz-Bolivia (3,600m) [11,811ft]). The logic behind it is that at all altitudes on planet Earth, life thrives in a 20.9% Oxygen, 79% Nitrogen. PaCO2 also needs to be considered. In a physiological manner, over 200 million inhabitants of high altitude above 2,000m [6,561ft], have perfectly normal lives. The astronauts could benefit of a Extra-Vehicular Activity (EVA) suit pressure of only 149 mmHg [2.8psi] (lighter, much more comfortable and efficient spacesuits) and space travel anemia could be reduced. The preparation prior-to-space travel could be carried out by adapting and living in a high altitude environment. We consider chronic hypoxia a fundamental step in BioSpaceForming (Adaptation to life in space). As all living beings start to move out of Earth into space, they will have to change their biology and adapt to new conditions.
Después del accidente del Apolo 1, ocurrido con 100 % de oxígeno en la cabina, todas las naves espaciales viajan con una presión de nivel del mar y 20,9 % de oxígeno. La actividad extravehicular requiere que se reduzcan las presiones. Es un proceso complejo que consume mucho tiempo. Reducir la presión de la cabina de manera permanente sería una gran ventaja. En un artículo de la NASA de 2013 se proponen las siguientes condiciones para el entorno de los vuelos espaciales: 8 psia / 32 % O2 (reduciendo la presión de nivel del mar (14,7 psi / 20,9 % O2), pero incrementando la fracción de oxígeno para replicar la PaO2 de nivel del mar). Sin embargo, nosotros nos cuestionamos esa propuesta, ya que está basada en el miedo a la hipoxia. La propuesta que hicimos en 2007 sugería que los vuelos espaciales se realizaran en un entorno hipobárico de 9,5 psi / 20,9 % O2 (como en la ciudad de La Paz, Bolivia (3 600 m) [11 811 ft]). El fundamento lógico es que en el planeta Tierra la vida se desarrolla a todas las alturas con 20,9 % oxígeno, 79 % nitrógeno, aunque también hay que tener en cuenta la PaCO2. Desde el punto de vista fisiológico, más de 200 millones de habitantes de grandes alturas de más de 2 000 m [6 561 ft] tienen una vida perfectamente normal. Para la Actividad Extra-Vehicular (EVA) a los astronautas les convendría más que el traje tuviera una presión de sólo 149 mmHg [2,8 psi], es decir, un traje más ligero y mucho más cómodo y eficiente, a la vez que se reduciría la ocurrencia de anemia espacial. La preparación previa al vuelo espacial podría basarse en la adaptación a un entorno de gran altitud y la vida en el mismo. Consideramos que la hipoxia crónica es un paso fundamental en la adaptación biológica y la supervivencia en el espacio. Todo organismo vivo que se traslade de la Tierra al espacio debe cambiar su biología y adaptarse a las nuevas condiciones.
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Background: Blood flow, metabolic rate and oxygenrequirements of an organ guide the extent of oxidativestress experienced by any tissue in response to chronichypoxia. Currently cilnidipine is used in themanagement of hypertension and its antioxidant actionsare gaining wide interest. Aim and Objectives: Toevaluate the tissue specific effects of chronic sustainedhypoxia with regards to oxidative stress in the contextof cilnidipine. Material and Methods: Twenty fouradult male Wistar strain albino rats were randomlyassigned into four groups: group 1, control, normoxia(21% O ); group 2, chronic hypoxia (CH) (10% O ) for 2 221 days; group 3, normoxia + cilnidipine (Cil) for 21days; group 4, chronic hypoxia + cilnidipine (CH+Cil)for 21 days. Following 21 days of intervention bloodwas collected and animals were sacrificed and liver,lung and heart were collected. Serum MDA and MDAin tissue homogenate of liver, lung and heart wereestimated. Results: Our results demonstrate theelevated serum MDAlevels in chronic hypoxia exposedrats (group 2). We also observed increased MDAin liverfollowed by lung and least in the heart in chronichypoxia exposed rats (group 2). Treatment withcilnidipine reduced serum MDA and heart MDA levelsin cilnidipine treated chronic hypoxia exposed rats(group 4). However cilnidipine did not have anyinfluence on MDA levels in the liver and lung in samegroup of rats. Conclusion: The results demonstratetissue specific effects of chronic sustained hypoxia withthe highest oxidative stress observed in the liverfollowed by the lung. Although oxidative stress is alsoobserved in the heart it is the least in comparison to theliver and the lung. Cilnidipine, a dual L/N type calciumchannel blocker demonstrated beneficial antioxidantactions only in the heart supporting the cardioprotectiverole of cilnidipine
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Aim To investigate the alteration of volt-age-depending potassium channel(KV) current in pul-monary arterial smooth muscle cells(PASMCs) of pul-monary hypertension (PH) rats, and the effect of tet-raethylammonium (TEA,a blocker of KV) on potassi-um channel current in different PH models. Methods The whole-cell patch clamp techniques were applied to record the KVcurrents from PASMCs cultured with Ham's F-12 (1% FBS). Furthermore, the effects of TEA on the KVcurrents were examined in different PH models. Results The whole-cell KVcurrents were ob-viously inhibited in PASMCs of chronic hypoxia (CH)and monocrotaline (MCT)-treated rats. TEA signifi-cantly decreased the whole-cell KVcurrents in PASMCs of control and PH rats,and the inhibitory effect of TEA was dramatically reduced in PH group. Conclusions The degree of the voltage-dependent potassium chan-nels opening is significantly inhibited in PASMCs of CH and MCT-treated rats,accordingly,the TEA-sen-sitive KVcurrents obviously decrease.
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Animal models of pulmonary artery hypertension (PAH),aiming to simulate human characteristics of the disease,have contributed extensively to understanding the pathophysiology of PAH and the investigation of experimental treatments.The classical models include monocrotaline models,chronic hypoxia model and so on,more new models were investigated in recent years.These animal models were not able to perfectly mimic human pathological characteristics of PAH because of the defect in different aspects.In this review,both typical and novel methods of PAH modeling were summarized and evaluated to provide a suitable guidance for the settlement of animal models which can meet human characteristics comprehensively.
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The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley (SD) rats were randomly divided into three groups: the control, model, and treatment groups (n = 10 per group). The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill (35 mg·kg(-1)·d(-1)) for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor 1α (HIF-1α) were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1α expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular diseases.
Subject(s)
Animals , Apoptosis , Cardiomyopathies , Drug Therapy , Metabolism , Pathology , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Heart , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Myocardium , Metabolism , Pathology , Oxygen , Metabolism , Phytotherapy , Rats, Sprague-DawleyABSTRACT
Although it was thought that survivors from an acute kidney injury (AKI) recovered kidney function completely, cumulative observational data have shown that AKI can cause end-stage renal disease directly, increase the risk of developing incident chronic kidney disease (CKD), and worsen an underlying CKD. These data have confirmed an association between AKI and an increased risk of permanent kidney damage, with subsequent development of CKD. However, many studies have focused on early injury following ischemic insult; the mechanisms of long-term injury remain poorly understood. Established and new data suggest that endothelial injury, loss of peritubular capillary volume, and chronic hypoxia affect structural changes after an ischemic insult. The repair process after acute kidney injury can be both adaptive and maladaptive. A maladaptive response includes persistent upregulation of proinflammatory and profibrotic signals and maladaptive cellular regeneration; this is thought to be one of the mechanisms leading to progressive renal injury and, ultimately, end-stage renal disease. The purpose of this brief review was to focus on recent advances related to the mechanisms of the progression from AKI to CKD. This review suggests that a new approach is required to manage AKI patients to prevent and/or arrest CKD progression.
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Humans , Acute Kidney Injury , Hypoxia , Capillaries , Inflammation , Kidney , Kidney Failure, Chronic , Regeneration , Renal Insufficiency, Chronic , Survivors , Up-RegulationABSTRACT
Objective To explore the role of endothelial nitric oxide synthase(eNOS) in the regulatory effects of erythropoie‐tin (EPO) on mitochondiral biogenesis in cardiomyocytes exposed to chronic hypoxia .Methods H9c2 cardiomyocytes were cultured in the environment of hypoxia for 1 week(94% N2 ,5% O2 ) ,establishing the chronic hypoxic cardiomyocyte model .All the cells were divided into 3 groups :HC(chronic hypoxic control) ,HE[treated with chronic hypoxia and 20 U/mL recombinant human EPO (rhEPO) ]and HR(cells transfected with eNOS shRNA plasmid and treated with 20 U/mL rhEPO and chronic hypoxia) .Fluores‐cent probe was used to detect the changes of mitochondial number .Mitochondial DNA (mtDNA) relative express level was assayed by RT‐PCR .The expression and phosphorylation of eNOS protein were analyzed with Western blot .Results rhEPO significantly increased the phosphorylation of eNOS and elavated the mitochondialt number and mtDNA (P< 0 .05) .shRNA interference on eNOS significantly blocked all the above changes induced by rhEPO (P<0 .05) .Conclusion Phosphory lation of eNOS is the im‐portant signalling pathway for the enhanced mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia by EPO .
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Aim To evaluate the effects of notoginsen-oside R1 on store-operated calcium entry ( SOCE ) in pulmonary arterial smooth muscle cells ( PASMCs ) of chronic hypoxia ( CH)-and monocrotaline ( MCT)-in-duced pulmonary hypertension ( PH) rats. Methods Mn2+ quenching of Fura-2 and measurement of intra-cellular free calcium concentration ( [ Ca2+] i ) using fluo-3 were examined in PASMCs of CH-exposed and MCT-treated rats. Results ①CH-exposed and MCT-treated rats exhibited profound PH when examined 3 weeks after hypoxia exposure or MCT injection, respec-tively. ②In the presence of 3 μmol·L-1 nifedipine, 10 μmol · L-1 notoginsenoside R1 significantly re-duced cyclopiazonic acid ( CPA )-induced the percent reduction in Fura-2 fluorescence measured 500 sec af-ter application of Mn2+, the maximal rate of Mn2+quenching, the amplitude of the Ca2+ influx transient and the resting [ Ca2+] i in PASMCs of CH-exposed and MCT-treated rats. Conclusion Notoginsenoside R1 inhibits SOCE and reduces resting [ Ca2+] i in PASMCs of CH-and MCT-induced PH rats.
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Aim To evaluate the time-course curve of expression of TRPC1 and vascular tone of pulmonary arteries(PAs)mediated by SOCE in chronic hypoxia pulmonary hyperte-nsion rats.Methods Both tension of PA rings and expression of TRPC1 were tested in CH exposure (1 0.0 % ±0.5 %partialpressure ofoxygen ) induced pulmonary hypertensive (PH)rats,and the time-course curve(detected respectively in CH 1 ,3,5, 7,1 4,21 d)was traced.Results ①CH could up-regulate the mean right ventricular pressure(mRVSP) ,which was increased significantly on 1 d,and reached the maximum on 7d;right ventricular weight index (RV-MI)began increase on 3d,and kept rising;②semi-quantitative reverse transcription polyme-rase chain reaction (RT-PCR)was performed to detect the expression of TRPC1 in PAs.The expression of TRPC1 increased significantly on 1 d,and reached the maxi-mum on 3d;③CH could up-regulate the vascular tone of PAs mediated by SOCE,which was increased signif-icantly on 3d,and reached the maximum on 7d.Con-clusions TRPC1 /SOCE increases significantly in the early days of CH,and the time-course curve of the two has correlation,which reflects the important role of the upregulation of TRPC1 /SOCE in the process of chronic hypoxia pulmonary hypertension.
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Objective To investigate the metabolism change of intestinal flora due to chronic hypoxia in infants. Methods Ten infants with tetralogy of fallot were considered as the chronic hypoxia group,10 healthy infants were regarded as the control group. The urine concen-tration of hippurate in the morning with fasting was detected by 1 H nuclear magnetic resonance. Results The concentration of hippurate was decreased in hypoxia group compared with the control group,(47. 15 ± 32. 88) mg/L vs (346. 698 ± 13. 555) mg/L,with significant differ-ence,P=0. 002. Conclusion Chronic hypoxia alters metabolism of intestinal flora in infants.
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Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated K+ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane A2 (TXA2) and hypoxia-activated nonselective cation channel (I(NSC)) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and TXA2-activated I(NSC) was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased I(NSC) might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.
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Animals , Rats , 4-Aminopyridine , Hypoxia , Lung , Muscle Cells , Myocytes, Smooth Muscle , Pulmonary Artery , Thromboxane A2 , VasoconstrictionABSTRACT
BACKGROUND: α-lipoic acid is named as “nature antioxidant” and “mitochondrial nutrition”. But it is unclear whether α-lipoic acid can be used to protect skeletal muscle with chronic hypoxia exposure, as wel as the relative mechanism. OBJECTIVE: To observe the effect of α-lipoic acid on the antioxidant enzymes and oxidative stress in rat skeletal muscle with chronic hypoxia exposure, and to investigate the relative signaling pathway of α-lipoic acid. METHODS: Thirty-six Sprague Dawley rats were randomly divided into three groups: normoxia control group, hypoxia control group, and hypoxia+α-lipoic acid group. Rats in the hypoxia control group were subjected to hypoxia exposure in normobaric hypoxic tent with 11.3% oxygen concentration. Rats in the hypoxia+α-lipoic acid group were induced by adding α-lipoic acid (0.25%) in the normal diet. Al the interventions were lasted for 4 weeks. RESULTS AND CONCLUSION: α-lipoic acid in hypoxia could markedly enhance the mitochondrial Sirtuin-3 expression, improve the mitochondrial adenosine triphosphate synthesis activity and membrane potential, up-regulate the mitochondrial state 3 respiratory rate, respiratory control ratio and ratio of phosphorus to oxygen, down-regulate the mitochondrial state 4 respiratory rate and promote and up-regulate the activity of mitochondrial antioxidant enzymes such as manganese superoxide dismutase, glutathione peroxidase and catalase, thus inhibiting mitochondrial H2O2 generation rate and reducing mitochondrial malondialdehyde level. The results indicated that α-lipoic acid could improve the efficiency of energy metabolism of chronic hypoxia skeletal muscle mitochondria and inhibit reactive oxygen generation, and it could inhibit the oxidative stress through improving antioxidant enzyme activity of mitochondria. The protection mechanism of α-lipoic acid on hypoxia skeletal muscle mitochondria may be related to the increasing of mitochondrial state 3 respiratory rate.
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This study analyzed the time dependence decay of the mRNA of selected genes important for the hypoxia response. The genes chosen were the two isoforms of hypoxia-inducible factors, the three isoforms of the prolyl hydroxylase domain protein, the vascular endothelial growth factor and endothelial nitric oxide synthase. mRNA and proteins were extracted from lungs obtained from control, hypoxic and 15 minutes normoxic recovered rats and analyzed by Real-time RT-PCR or by the Western Blot technique. Results indicated that in normoxia isoform 2á was the more represented hypoxia-inducible factor mRNA, and among the prolyl hydroxylase domain transcripts, isoform 3 was the least abundant. Moreover, in chronic hypoxia only hypoxia-inducible factor 1α and prolyl hydroxylase domain protein 3 increased significantly, while after 15 minutes of recovery all the mRNAs tested were decreased except endothelial nitric oxide synthase mRNA. In terms of proteins, hypoxia-inducible 1α was the isoform more significant in the nucleus, while 2á predominated in the cytosol. While the former was steady even after a brief recovery from hypoxia, the latter underwent a strong degradation. In conclusion we showed the relevance of the decay in the mRNA and protein levels upon re-oxygenation in normoxia. We believe that this has to be considered in research studies dealing with recovery from hypoxia.
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Animals , Male , Hypoxia/genetics , Lung/metabolism , RNA, Messenger/metabolism , Transcription, Genetic/genetics , Blotting, Western , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Procollagen-Proline Dioxygenase/genetics , Procollagen-Proline Dioxygenase/metabolism , Rats, Wistar , Real-Time Polymerase Chain Reaction , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The chronic-hypoxia-resistant gastric cancer cell line was established,and its biological characteristics were explored and compared with the parental cell line.Gastric cancer cell lines were cultured under the degressive oxygen concentration.Cell doubling time was calculated by cell counting method.Chemo-resistance ability of cells was tested by MTT assay.Irradiation tolerance of cells was evaluated by colony forming method.Cell cycle distribution was tested with flow cytometry.Invasive ability was tested by Transwell method.The expression levels of GLUT-1 and HIF-1α were detected by using Western blot.MNK45/HYP cells successfully survived under the 1％ concentration of oxygen and its cell doubling time was 35.01±1.02 h,while that of MNK45 was 27.35±0.83 h (P＜0.01).The percentage of MNK45/HYP cells in G0/G1 stage was (58.3±6.1)％,and that of MNK45 cells was (42.2±6.0)％ (P＜0.05).Comparing with the parental cells MNK45,drug resistance indexes of 5-Fu,PTX,OXA,Sn38,GEM and VP16 in MNK45/HYP cells were respectively 5.3,1.3,3.6,2.2,4.8 and 4.4.Colony forming ability of MNK45/HYP cells after irradiation was also significantly higher than MNK45 cells.The invasive number of MNK45/HYP cells was 107.7±17.5,while that of MNK45 cells was 59.0±9.9.The expression levels of GLUT-1 and HIF-1α in MNK45/HYP cells were significantly higher than those in MNK45 cells.MNK45/HYP cells hold biological characteristics of hypoxia tumor with good tolerance to chronic hypoxia,and can be used for the research of solid tumor under chronic hypoxia condition.
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Lung disease with chronic hypoxia has been associated with cognitive impairment of the subcortical type. Objectives: To review the cognitive effects of chronic hypoxia in patients with lung disease and its pathophysiology in brain metabolism. Methods: A literature search of Pubmed data was performed. The words and expressions from the text subitems including ?pathophysiology of brain hypoxia?, ?neuropsychology and hypoxia?, ?white matter injury and chronic hypoxia?, for instance, were key words in a search of reports spanning from 1957 to 2009. Original articles were included. Results: According to national and international literature, patients with chronic obstructive pulmonary disease and sleep obstructive apnea syndrome perform worse on tests of attention, executive functions and mental speed. The severity of pulmonary disease correlates with degree of cognitive impairment. These findings support the diagnosis of subcortical type encephalopathy. Conclusion: Cognitive effects of clinical diseases are given limited importance in congresses and symposia about cognitive impairment and its etiology. Professionals that deal with patients presenting cognitive loss should be aware of the etiologies outlined above as a major cause or potential contributory factors, and of their implications for treatment adherence and quality of life.
As doenças pulmonares que cursam com hipóxia crônica tem sido associadas à alteração cognitiva do tipo subcortical. Objetivo: Revisar os efeitos cognitivos da hipóxia crônica em pacientes com doenças pulmonar e sua fisiopatologia. Métodos: Foi utilizado o banco de dados do Pubmed. As palavras e expressões foram os temas dos subitens da revisão como, por exemplo, ?fisiopatologia e hipóxia cerebral?, ?neuropsicologia e hipoxia?, ?lesões de substância branca e hipóxia crônica?, variando de 1957 to 2009. Artigos originais foram incluídos. Resultados: De acordo com a literatura nacional e internacional, pacientes com doença pulmonar obstrutiva crônica e síndrome da apnéia obstrutiva do sono apresentam desempenho pior em testes neuropsicológicos que avaliam atenção, funções executivas e velocidade de processamento mental. Esses achados configuram uma encefalopatia do tipo subcortical. Conclusion: É dada importância limitada às conseqüências cognitivas das doenças clínicas em congressos e simpósios sobre cognição e suas etiologias. Profissionais que lidam com pacientes que apresentam perda cognitiva devem suspeitar das etiologias mencionadas acima com causa principal ou como co-fatores, assim com suas implicações na aderência ao tratamento e qualidade de vida.
Subject(s)
Humans , Brain Diseases , Hypoxia, Brain , Cognition , Cerebrum , Hypoxia , Neuropsychological TestsABSTRACT
Chronic sublethal hypoxia induces brain adaptations associated with changes in neurovascular behavior. Changes to the neurovasculature also influence the formation of the brain-blood barrier (BBB). In this study, I investigated the influence of chronic sublethal hypoxia on astrocytes, using the coculture transwell model of primary cultured astrocytes and RBE4 (brain endothelial) cells. Using a 3D collagen gel model, cytoplasmic processes of astrocytes extended to clumps of endothelial cells. The numbers of astrocytes increased in cocultured and chronic hypoxic environments in the transwell model. Western blotting showed increased production of glial fibrillar acidic protein (GFAP) and proliferating cellular nuclear antigen (PCNA) in chronic hypoxia. I also confirmed the influence of hypoxia on the behavior of astrocytes in this model, using confocal microscopy. The numbers of cytoplasmic processes of astrocytes within the membrane increased in z sections. These data support the idea that chronic hypoxia might induce alterations in the formation of the BBB as part of the adaptation of the brain to chronic hypoxia. These transwell and 3D collagen gel models will probably be useful for functional as well as morphological experiments.
Subject(s)
Hypoxia , Astrocytes , Blood-Brain Barrier , Blotting, Western , Brain , Coculture Techniques , Collagen , Cytoplasm , Endothelial Cells , Membranes , Microscopy, ConfocalABSTRACT
Chronic hypoxia has been associated with change in neurovascular behavior, mediated, in part, by erythropoietin (EPO). EPO, a hematopoietic growth factor, could act as a neurotrophic factor. In the present study, we investigated the characteristics of EPO and erythropoietin receptor (EPOR) expressions by cortical neuron in vivo and in vitro and tested the hypothesis that EPO serves protective functions under chronic hypoxia. E18, P5 and P7 mice for 3 days and primary cultured neurons for 6 days were incubated in hypoxic conditions consisted of a mixture of 10% O2, 5% CO2, 85% N2. To study expressions of EPO, EPOR, caspases, pAKT, pERK, and PARP, immunohistochemical stainning and western blotting were carried out. In addition to expressing EPO and EPOR under normoxic conditions, neurons increased their expression of EPO and EPOR under hypoxia. The effects of recombinant EPO appeared to be mediated via the phosphatidylinositol (PI) 3- kinase-AKT pathway, correlated directly with activation of caspase 3. Also recombinant EPO decreased expression of caspase 8, but not caspase 9. Finally, recombinant EPO decreased apoptosis of cultured neurons as evaluated by expression of PARP. These data support a role for EPO in maintenance of cortical neuron under chronic hypoxia.