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Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1–20 mg/kg (in vivo) and 0.5–5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments. [ABSTRACT FROM AUTHOR]

This is the case of a 26-year-old male who developed Anton Babinski syndrome (ABS), quadriplegia, and delayed post-hypoxic leukoencephalopathy (DPHL) after an opioid overdose. He exhibited cortical blindness, visual anosognosia, and confabulation upon awakening. Several days later, he experienced acute psychosis and agitation. T2-FSE MRI revealed extensive supratentorial leukoencephalopathy involving both cerebral hemispheres, extending to the posterior corpus callosum due to cerebral anoxia. This case report will discuss different types of encephalopathy from opioid abuse, ABS, visual anosognosia, and confabulation's pathogenic mechanisms. It underscores the necessity of researching substance-induced neuropsychiatric disorders and their pathogenic mechanisms for effective treatments. [ABSTRACT FROM AUTHOR]

Cerebral stroke is a serious clinical condition in which oxidative stress, inflammation, necrosis, apoptosis, and autophagy play important roles in its pathogenesis. This study investigated the neuroprotective and healing effects of calcium dobesilate (CD) on cerebral hypoxia/reperfusion injury in rats. Forty Wistar albino male rats, each weighing 300–350 g, were separated into the Control group (no surgery and no pharmacological agent was administered); Sham-A group (only surgery was performed); DBL-A group (surgery was performed and CD 100 mg/kg/day was administered intraperitoneally for 3 days); Sham-C group (only surgery was performed); and DBL-C group (surgery was performed and 100 mg/kg/day CD was administered intraperitoneally for 10 days). Under sedation anesthesia, the bilateral common carotid arteries of all rats except the Control group were clipped for 30 min. After 4 h, the CD was given to the relevant groups, and then, all subjects were euthanized at scheduled times. The brain of each animal was removed for histopathological (hematoxylin and eosin staining), immunohistochemical (beclin-1, anti-MHC class II and anti-CD-68 staining), and biochemical (TNF, IL-1β, IL-6, caspase-3, GSH/GSSG, malondialdehyde, protein carbonyl, LC3II/LC3I, and beclin-1 levels) evaluations. It was observed that CD could reduce necrosis and mitigate polarization of microglia to the M1 phenotype, autophagy, free oxygen radicals, protein carbonylation, lipid peroxidation, IL-1β, IL6, TNF, caspase-3, beclin-1, and LC3II/LC3I levels in acute and chronic periods of hypoxia/reperfusion injury. From these results, it was observed that CD treatment could reduce neuronal necrosis and create anti-inflammatory, anti-edema, anti-oxidant, anti-apoptotic, and anti-autophagic effects in hypoxia/reperfusion injury in rats. [ABSTRACT FROM AUTHOR]

This prospective study investigated and analyzed the clinical characteristics and prognosis of paroxysmal sympathetic hyperactivity (PSH) in patients with severe nontraumatic brain injury. Patients presenting with severe nontraumatic brain injury with PSH from July 2018 to June 2019 were enrolled. A PSH assessment measure ≥ 8 points was used as the criterion for PSH. Clinical data, indicators related to PSH, treatment effects and the prognosis were prospectively collected and analyzed. A total of 220 patients with severe nontraumatic brain injury were analyzed, and PSH occurred in 8 patients (3.6%). The primary neurological diseases included acute cerebral infarction, anti-N-methyl-D-aspartate receptor encephalitis, hypoxic encephalopathy and acute disseminated encephalitis. The Glasgow Coma Scale score was lower than 8 in the 8 patients with PSH. Seven of these eight patients had a Glasgow outcome scale (GOS) score of 3 or less than 3, and one patient had a GOS of 5 after 6 months. The medicines that effectively controlled PSH included dexmedetomidine, clonazepam, midazolam and diazepam. Although the incidence was lower for nontraumatic brain injury complicated with PSH than for traumatic brain injury, patients with PSH had a more severe disease state and poorer prognoses. Dexmedetomidine might effectively control PSH. [ABSTRACT FROM AUTHOR]

The article aims to raise awareness of suicide through a discussion about a severely abnormal electroencephalogram (EEG) recording of a patient in her mid-40s who was found unresponsive after a suicide-attempt by helium inhalation. Topics covered include an evaluation of the patient's brain dysfunction, depth of coma, possible non-convulsive status epilepticus, and reactivity found by the EEG, a discussion of the EEG findings, and patient outcome following treatment.

To investigate the role and mechanism of miR-17-5p in cerebral hypoxia/reoxygenation (H/R)-induced apoptosis. The present study used human brain microvascular endothelial cells (HBMVECs) to establish cerebral H/R model. MTT was used to measure the cell viability. Flow cytometry was used to detect the cell apoptosis. The interaction between miR-17-5p and PTEN was determined using dual luciferase reporter assay. RT-qPCR and Western blotting were used for determination of the expression of miR-17-5p, PTEN, apoptosis- and PI3K/AKT/mTOR signalling-related proteins. The cell viability and the expression of miR-17-5p were obviously down-regulated while the expression of PTEN was obviously up-regulated in H/R cells. The cell viability was remarkably enhanced, and the cell apoptosis induced by H/R injury was dramatically reduced when miR-17-5p was overexpressed in HBMVECs under H/R condition, which was reversed by overexpression of PTEN. Dual luciferase reporter assay showed PTEN was a direct target of miR-17-5p. Treatment of PI3K inhibitor LY294002 significantly increased the apoptosis rate of HBMVECs, and this effect was significantly reversed by transfection of miR-17-5p mimics, while further dramatically enhanced by overexpression of PTEN. MiR-17-5p could ameliorate cerebral I/R injury-induced cell apoptosis by directly targeting PTEN and regulation of PI3K/AKT/mTOR signalling. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic encephalopathy (HIE) is the result of global hypoxic-ischemic brain injury in neonates due to asphyxia during birth and is one of the most common causes of severe, long-term neurologic deficits in children. Methods: Resting state fMRI (rs-fMRI) was used to assess potential functional disruptions in the primary and association motor areas in HIE neonates (n = 16) compared to healthy controls (n = 11). Results demonstrate reduced intra-hemispheric resting state functional connectivity (rs-FC) between primary motor regions (upper extremity and facial motor regions) as well as reduced inter-hemispheric rs-FC in the HIE group. In addition, HIE neonates demonstrated increased rs-FC between motor regions and frontal, temporal and parietal cortices but decreased rs-FC with the cerebellum. These preliminary results provide initial evidence for the disruption of functional communication with the motor network in neonates with HIE. Further studies are necessary to both validate these findings in a larger dataset as well as to determine if rs-fMRI measurements collected at birth may have the potential to serve as a prognostic marker in addition to the traditional combination of clinical measurements and conventional MRI. [ABSTRACT FROM AUTHOR]

The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120-130nm with well-developed pore structure (SBET: 1009.94 m2/g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min. [ABSTRACT FROM AUTHOR]

Although the treatment of brain tumors by targeting kinase-regulated macroautophagy/autophagy, is under investigation, the precise mechanism underlying autophagy initiation and its significance in glioblastoma (GBM) remains to be defined. Here, we report that PAK1 (p21 [RAC1] activated kinase 1) is significantly upregulated and promotes GBM development. The Cancer Genome Atlas analysis suggests that the oncogenic role of PAK1 in GBM is mainly associated with autophagy. Subsequent experiments demonstrate that PAK1 indeed serves as a positive modulator for hypoxia-induced autophagy in GBM. Mechanistically, hypoxia induces ELP3-mediated PAK1 acetylation at K420, which suppresses the dimerization of PAK1 and enhances its activity, thereby leading to subsequent PAK1-mediated ATG5 (autophagy related 5) phosphorylation at the T101 residue. This event not only protects ATG5 from ubiquitination-dependent degradation but also increases the affinity between the ATG12–ATG5 complex and ATG16L1 (autophagy related 16 like 1). Consequently, ELP3-dependent PAK1 (K420) acetylation and PAK1-mediated ATG5 (T101) phosphorylation are required for hypoxia-induced autophagy and brain tumorigenesis by promoting autophagosome formation. Silencing PAK1 with shRNA or small molecule inhibitor FRAX597 potentially blocks autophagy and GBM growth. Furthermore, SIRT1-mediated PAK1-deacetylation at K420 hinders autophagy and GBM growth. Clinically, the levels of PAK1 (K420) acetylation significantly correlate with the expression of ATG5 (T101) phosphorylation in GBM patients. Together, this report uncovers that the acetylation modification and kinase activity of PAK1 plays an instrumental role in hypoxia-induced autophagy initiation and maintaining GBM growth. Therefore, PAK1 and its regulator in the autophagy pathway might represent potential therapeutic targets for GBM treatment. Abbreviations: 3-MA: 3-methyladenine; Ac-CoA: acetyl coenzyme A; ATG5: autophagy related 5; ATG16L1, autophagy related 16 like 1; BafA1: bafilomycin A1; CDC42: cell division cycle 42; CGGA: Chinese Glioma Genome Atlas; CHX, cycloheximide; ELP3: elongator acetyltransferase complex subunit 3; GBM, glioblastoma; HBSS: Hanks balanced salts solution; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MAP2K1: mitogen-activated protein kinase kinase 1; MAPK14, mitogen-activated protein kinase 14; PAK1: p21 (RAC1) activated kinase 1; PDK1: pyruvate dehydrogenase kinase 1; PGK1, phosphoglycerate kinase 1; PTMs: post-translational modifications; RAC1: Rac family small GTPase 1; SQSTM1: sequestosome 1; TCGA, The Cancer Genome Atlas. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) to the tails of the core histone proteins are critically involved in epigenetic regulation. Hypoxia affects histone modifications by altering the activities of histone-modifying enzymes and the levels of hypoxia-inducible factor (HIF) isoforms. Synthetic hypoxia mimetics promote a similar response, but how accurately the hypoxia mimetics replicate the effects of limited oxygen availability on the levels of histone PTMs is uncertain. Here we report studies on the profiling of the global changes to PTMs on intact histones in response to hypoxia/hypoxia-related stresses using liquid chromatography-mass spectrometry (LC-MS). We demonstrate that intact protein LC-MS profiling is a relatively simple and robust method for investigating potential effects of drugs on histone modifications. The results provide insights into the profiles of PTMs associated with hypoxia and inform on the extent to which hypoxia and hypoxia mimetics cause similar changes to histones. These findings imply chemically-induced hypoxia does not completely replicate the substantial effects of physiological hypoxia on histone PTMs, highlighting that caution should be used in interpreting data from their use. [ABSTRACT FROM AUTHOR]

The somatic effects of empire can be found in Tim Winton's "pneumatic materialism", an aesthetic preoccupation in his novels with moments of anoxia, or the deprivation of oxygen to the brain. This essay will consider how Winton's novel engage with pneumatic materialism in response to questions of uneven development traditionally associated with the Global South, thereby disrupting clear South–North distinctions. By blurring his concerns across the North–South divide, Winton shows a willingness to think of empire as a series of relations that are not bound by national or territorial borders so much as by substances in the air. He does this, I argue, in his use of the breath. [ABSTRACT FROM AUTHOR]

This study explored the utility of the Coma Recovery Scale-Revised (CRS-R) in predicting emergence from a disorder of consciousness, using a sample of veterans who were treated at one of the five Veterans Affairs (VA) polytrauma rehabilitation centre sites in an Emerging Consciousness programme. Participants (N = 70) included both combat and non-combat active duty military personnel and veterans who sustained either a severe traumatic brain injury, or anoxic brain injury and were considered to have a disorder of consciousness at the time of admission. Patient information was retrospectively collected from electronic medical records from one of the VA polytrauma rehabilitation centre sites. Receiver Operator Characteristic models were utilised to explore "cut-off scores" for predicting emergence using the CRS-R. Results showed that week-three scores on the CRS-R were more accurate in determining whether a veteran would emerge from a disorder of consciousness. Limitations, including a limited sample size are explored, along with implications and recommendations for future research and clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: In Denmark, specialised neurorehabilitation is centralised in two centres; one is Hammel Neurocentre. The neurointensive stepdown unit at Silkeborg Regional Hospital offers intensive care in addition to specialised neurorehabilitation of patients transferring to Hammel. Knowledge on patient's characteristics and course of rehabilitation in this kind of setting is sparse. Objective: To characterise the patients, their change in function and to identify variables associated with referral time to Hammel. Methods: Functional scores and available covariates were extracted from hospital records on 251 patients admitted from 01 November 2011 to 31 July 2016. Statistical methods included logistic regression and paired tests. Results: Mean (standard deviation) time from injury to admission at the neurointensive stepdown unit was 30 (22) d, medians (interquartile range) of Functional Independence Measure and Early Functional Abilities increased significantly from 18 (18, 19) to 24 (18, 44) and 37 (30, 46) to 52 (43, 70), respectively, during admission (p < 0.01). Spontaneous ventilation and Early Functional Abilities score on admission were positively associated with early referral. Obesity and anoxic brain injury were negatively associated with early referral. Conclusions: This study demonstrated functional improvement in patients in a neurointensive stepdown unit and identified variables associated with early referral. The study indicated higher sensitivity of the Early Functional Abilities score as compared to the Functional Independence Measure. Patients requiring prolonged intensive care services after severe acquired brain injury may require the fusion of neurorehabilitation and intensive care services to benefit maximally. There is a need for a consensus on which functional scores to use when documenting functional level and functional changes in patients with severe acquired brain injury and very low functional levels. The Early Functional Abilities score is an example of a valuable tool when assessing functional levels of patients with severe acquired brain injury and very low functional levels. [ABSTRACT FROM AUTHOR]

Primary Objective: The aim of this study was to demonstrate the clinical outcomes of long-term multidisciplinary attentive treatment (MAT) in patients with chronic disorders of consciousness (DOC) due to severe traumatic brain injury (TBI) following automotive accidents. Research Design: Five hundred and ten patients (mean age: 40.4 years) were enrolled in this retrospective study. Methods and Procedures: Patients were provided MAT for one to several years in the eight medical facilities of the National Agency for Automotive Safety and Victims' Aid (NASVA) in Japan. Clinical status for consciousness, communication, and activities of daily living were evaluated using the NASVA grading system. Outcomes and results: Following MAT, NASVA scores at discharge were significantly improved compared to those at admission in every patient subgroup including sex, age, NASVA score, and association with/without hypoxic encephalopathy at admission. Younger age, shorter interval between injury and admission, and better neurocognitive function at admission were found to be significant and independent factors for a good prognosis. Conclusions: MAT can partially improve the cognitive and physical abilities of patients with chronic DOC. From the perspective of not only restoring a patient's daily life, but also reducing the caregiver's burden, this type of treatment program warrants more public attention. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the prognostic value of demographical, anamnestic, and clinical findings on long-term outcome (up to 36 months) in individuals with severe brain injury in vegetative state (VS) or in minimally conscious state (MCS). Participants. Patients (N = 216) in VS (N = 159) or in MCS (N = 57) consecutively admitted to a neurorehabilitation unit within 1-3 months after severe anoxic (n = 71), vascular (n = 96), or traumatic (n = 49) brain injury. Main outcome. Mortality and improvements in clinical diagnosis at 12, 24, and 36 months after brain injury. Multivariable logistic regression analyses were performed to verify independent relationships of variables collected at study entry with outcome measures. Results. In patients in VS, at the 12-month follow-up, higher level of responsiveness assessed by the Coma Recovery Scale-Revised (CRS-R) total scores at study entry predicted a higher likelihood of both survival and clinical improvement, whereas younger age predicted survival only. At 24 months, female sex and higher CRS-R total scores tended to be associated with clinical improvements. In patients in MCS, younger age and female predicted consciousness recovery at 12 months. Conclusions. Several patients' features easy to collect in rehabilitation setting might help clinicians in prognostication of long-term mortality and clinical evolution of VS and MCS. [ABSTRACT FROM AUTHOR]

A 2-year-old male pediatric patient experienced a partial occlusion of the internal carotid and subsequent asphyxiation resulting in hypoxic brain injury that was later misdiagnosed as primary attention deficient hyperactivity disorder (ADHD). Imaging analyses using diffusion tensor imaging (DTI), positron emission tomography (PET), and magnetic resonance imaging (MRI) quantitative volumetrics (QV) were used nine years following the incident to identify whether his development of ADHD is of a primary heritability or secondary hypoxic brain injury sequelae. The patient's DTI analysis generated decreases in fractional anisotropy (FA) values in the anterior corpus callosum, bilateral internal capsule, and hippocampus. Decreases in FA are seen in ADHD patients, but the degree of FA decrease in the patient under study is several orders of magnitude greater than in ADHD patients. Also, not normally observed in ADHD patients were decreases in the metabolism of the orbitofrontal cortex, anterior cingulate, left anterior insular cortex, and left striatum. Additionally, QV showed enlargements of various regions of the brain including the amygdala which is often cited in the literature to be reduced in ADHD patients. The diagnosis of this patient despite having non-characteristic neuroimaging data suggests a unique specificity of the hypoxic injury to the development of a secondary hypoxic brain injury caused ADHD. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the biological significance of heat shock protein (HSP70) in adaptation to high altitude hypoxia. Methods: Ninety male SD rats were randomly divided into 10 groups: Acute plateau hypoxia group (group 5) and chronic high altitude hypoxia group (group 3), and control group (group 2).Changes in HSP gene and HSP protein expression in brain tissues of SD rats at different altitudes were determined by Western blot and conventional RT-PCR, while an optical and transmission electron microscope was used to observe the cell structure changes of animal brain tissues. Results: HSP70 expression rapidly increased at high altitudes in SD rats under high-altitude hypoxia environments, and HSP70 increased with altitude. Morphological and structural damage in SD rats in each group increased with altitude. Conclusion: The rapid synthesis of HSP70 in heat shock response is beneficial for maintaining the normal physiological function of cells during hypoxia stress, and the amount of HSP70 production is positively correlated with hypoxia tolerance ability. [ABSTRACT FROM AUTHOR]

Background: A long-term follow-up study comparing children after anoxic brain injury (AnBI) with those after traumatic brain injury (TBI) was conducted, and prognostic factors were mapped.Methods: A prospective historical study following long-term functional outcome after childhood brain injury was conducted in two phases. The first phase included patients suffering from moderate-severe TBI. The second phase assessed children after AnBI, and the results were compared. Functional outcome was recorded and factors influencing prognosis were outlined.Results: On admission vegetative state (VS) was twice as prevalent in the AnBI subgroup. Approximately 90% of children with TBI and 60% of patients with AnBI gained independency in activities of daily living (ADL) and mobility. Long-term positive outcome, i.e., return to school and open-market employment, were higher in patients with TBI when compared with AnBI (61% and 48.1%, respectively). Significant outcome-predicting factors were VS at admission to rehabilitation, length of loss of consciousness (LOC) up to 11 days and functional independence measure (FIM) score at admission and discharge. Aetiology was not found to be a predicting factor.Conclusions: Duration of unconsciousness is the main long-term negative prognostic outcome factor. Anoxic brain damage, associated with longer periods of unconsciousness also heralds a less favourable outcome. [ABSTRACT FROM AUTHOR]

Purpose:Investigate health care providers’ perceptions of referral and admission criteria to brain injury inpatient rehabilitation in two Canadian provinces. Methods:Health care providers (n = 345) from brain injury programs (13 acute care and 16 rehabilitation facilities) participated in a cross-sectional web-based survey. The participants rated the likelihood of patients (traumatic brain injury and cerebral hypoxia) to be referred/admitted to rehabilitation and the influence of 19 additional factors (e.g., tracheostomy). The participants reported the perceived usefulness of referral/admission policies and assessment tools used. Results:Ninety-one percent acute care and 98% rehabilitation participants reported the person with traumatic brain injury would likely or very likely be referred/admitted to rehabilitation compared to respectively 43% and 53% for the patient with hypoxia. Two additional factors significantly decreased the likelihood of referral/admission: older age and the combined presence of minimal learning ability, memory impairment and physical aggression. Some significant inter-provincial variations in the perceived referral/admission procedure were observed. Most participants reported policies were helpful. Similar assessment tools were used in acute care and rehabilitation. Conclusions:Health care providers appear to consider various factors when making decisions regarding referral and admission to rehabilitation. Variations in the perceived likelihood of referral/admission suggest a need for standardized referral/admission practices.Implications for RehabilitationVarious patient characteristics influence clinicians’ decisions when selecting appropriate candidates for inpatient rehabilitation.In this study, acute care clinicians were less likely to refer patients that their rehabilitation counter parts would likely have admitted and a patient with hypoxic brain injury was less likely to be referred or admitted in rehabilitation than a patient with a traumatic brain injury.Such discrepancies suggest that policy-makers, managers and clinicians should work together to develop and implement more standardized referral practices and more specific admission criteria in order to ensure equitable access to brain injury rehabilitation services. [ABSTRACT FROM PUBLISHER]

Purpose:Tumor resistance towards radiation has been a big obstacle in the poor prognosis of lung cancer. It has been reported that hypoxia and autophagy partly contribute to this resistance. However, there is controversy over whether autophagy plays a positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. Materials and methods:A549 cells were treated with conditioned medium (CM) under 12 h hypoxia or normoxia before irradiation, followed by the measurement of clonogenic survival, reactive oxygen species (ROS), signal of mitochondria and autophagy flux. In some experiments, the A549 cells were respectively transfected with LC3 small interfering RNA (siRNA), or treated with Earle’s Balanced Salt Solution (EBSS). Results:We found that hypoxia enhanced cell radioresistance by increasing the induction of autophagy. And after hypoxia stress, the number of mitochondria was reduced but the cellular ROS level was enhanced. It was significant that autophagy may enhance cell radioresistance by reducing ROS during hypoxic treatment. Conclusions:We elucidated the possible mechanisms of autophagy in regulating cancer cell death or survival. These results supply a new opinion about the intrinsic factor of radioresistance of hypoxia tumors. [ABSTRACT FROM AUTHOR]

Background: Anoxia can result in selective hippocampal damage with associated impairments in declarative memory. Whilst memory impairments and brain structures are thought to be stable, there are little data regarding the effects of ageing or change over time in patients with amnesia from anoxic brain injury. Methods: To assess change over time, we compared structural magnetic resonance imaging (MRI) with data obtained over ten years previously in two well-characterized patients with amnesia (JRW and RS) who experienced an anoxic brain injury. Six healthy, age-matched control participants were recruited to compare brain volumes with the patients at Time 2. Wechsler adult intelligence scale-revised and Wechsler memory scale-revised scores were compared to scores on the same tests administered 13 and 19 years prior. Results: Patients with amnesia had significantly smaller hippocampal volumes than controls, but comparable medial temporal lobe and ventricular volumes. Memory, intellectual function and brain volumes were stable over time. Conclusion: Patients with an amnesia due to anoxia have memory impairments and smaller hippocampal volumes compared to controls; however, memory, intelligence and structural volumes remain stable over time. At ages 50 and 57, they do not appear to have early age-associated cognitive decline that is sometimes observed in patients with traumatic brain injury. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate changes in self-awareness impairments in outpatients with acquired brain injury (ABI) and the effects these changes have on rehabilitation. Participants were 78 patients with ABI (8.3 years post-injury) who followed an intensive outpatient neuropsychological rehabilitation programme. This longitudinal study comprised pre (T1) and post (T2) measurements and a one-year follow-up (T3). Thirty-eight patients completed the study. The main outcome domains were self-awareness, depressive symptoms, psychological and physical dysfunction, and health-related quality of life (HRQoL). Patients were divided into three awareness groups: underestimation, accurate estimation, and overestimation of competencies. Most patients who underestimated their competencies at the start of treatment accurately estimated their competencies directly after treatment (9 out of 11 patients). These patients also exhibited the largest treatment effects regarding depressive symptoms, psychological and physical dysfunction, and HRQoL. Most patients with impaired self-awareness (i.e., overestimation of competencies) at the start of treatment continued to overestimate their competencies after treatment (10 out of 14 patients). These patients exhibited a significant decrease in depressive symptoms but no other treatment effects. The results indicate that changes in outcome are related to changes in awareness, which underline the importance of taking into account different awareness groups with respect to treatment effects. [ABSTRACT FROM PUBLISHER]

Objective: To determine whether transient hypoxia during breath-hold diving causes neuronal damage or dysfunction or alters amyloid metabolism as measured by certain blood biomarkers. Design: Sixteen divers competing in the national Swedish championship in breath-hold diving and five age-matched healthy control subjects were included. Blood samples were collected at baseline and over a course of 3 days where the divers competed in static apnea (STA), dynamic apnea without fins (DYN1) and dynamic apnea with fins (DYN2). Main outcomes: Biomarkers reflecting brain injury and amyloid metabolism were analysed in serum (S-100β, NFL) and plasma (T-tau, Aβ42) using immunochemical methods. Results: Compared to divers’ baseline, Aβ42 increased after the first event of static apnea (p= 0.0006). T-tau increased (p= 0.001) in STA vs baseline and decreased after one of the dynamic events, DYN2 (p= 0.03). Further, T-tau correlated with the length of the apneic time during STA (ρ= 0.7226,p= 0.004) and during DYN1 (ρ= 0.66,p= 0.01). Conclusion: The findings suggest that transient hypoxia may acutely increase the levels of Aβ42 and T-tau in plasma of healthy adults, further supporting that general hypoxia may cause mild neuronal dysfunction or damage and stimulate Aβproduction. [ABSTRACT FROM PUBLISHER]

Phil Bryden was a seminal figure in the development of the field of cerebral lateralization in the last half of the twentieth century, and a founding editor of this journal. Here his founding co-editors reminisce about their friend and colleague, and reflect on his wide-ranging influence in the field and in their own careers. [ABSTRACT FROM PUBLISHER]

We have seen a patient with a profound, isolated, and quite selective deficit in proverb interpretation—aproverbia. The patient presented to us after an anoxic brain injury with aproverbia. Interestingly, the aproverbia appeared to be premorbid to the presenting event. Furthermore, the patient had no brain lesion that has been associated or even proposed as a cause of deficit in proverb or metaphor interpretation. The patient did have acute bilateral hippocampi lesions and associated severe anterograde amnesia, but he retained good retrograde memory with which he is able to give good, logical but concrete explanations for proverbs. This case highlights the need, importance, and interest in further neuropsychologic, imaging and functional studies of proverb and interpretation in patients and normal subjects populations. [ABSTRACT FROM PUBLISHER]

Aim: Circulating immune cell activation is associated with worse outcome in adult and animal models of brain injury. Our aim was to profile the systemic inflammatory response over the first week of life in infants at risk of neonatal encephalopathy (NE) and correlate early neutrophil and monocyte endotoxin and activation responses with outcome.Methods: Prospective observational study in a tertiary referral university hospital including 22 infants requiring resuscitation at birth who had serial (five time points) neutrophil and monocyte CD11b (marker of cell adhesion), intracellular reactive oxygen intermediates (ROI; cell activation) and Toll-like receptor (TLR; endotoxin recognition) before and after endotoxin stimulation ex vivo compared to neonatal controls.Results: All neonates requiring resuscitation at delivery (n = 122 samples) had higher neutrophil and monocyte CD11b and TLR-4 expression compared with adults and neonatal controls. Neonates with abnormal neuroimaging and/or severe NE had increased CD11b, ROI and TLR-4. Increased polymorphonuclear leukocytes TLR-4 expression was associated with increased mortality in infants with NE.Conclusion: Innate immune dysregulation in the first week of life is associated with severity of outcome in neonatal brain injury in this cohort and may be amenable to immunomodulation. [ABSTRACT FROM AUTHOR]

Objectives: (1) To evaluate cognitive and emotional impairments, disability and quality-of-life for adults with cerebral anoxia institutionalized in residential care facilities. (2) To evaluate the efficacy of medication, psychotherapy, support group and therapeutic activities. Methods: Twenty-seven persons with cerebral anoxia were recruited, on average 8 years post-injury. Only 20 went through the whole study. Over three consecutive 2-month periods, they were assessed four times to evaluate: baseline observations (T1–T2), adjustment of their medication (T2–T3); and the effect of psychotherapy, support group and therapeutic activities such as physical and artistic or cultural activities usually proposed in the facilities involved (T3–T4). Examined variables at all time points were cognitive status, anxiety and depression, anosognosia, alexithymia, disability and quality-of-life. Results: All participants exhibited cognitive and emotional impairments comparable to those reported in the literature. Statistical analyses revealed good baseline stability of their condition and no significant effects of changes in medication (between T2 and T3). Conversely, following implementation of psychotherapy, support group and therapeutic activities (between T3 and T4), quality-of-life and social participation were significantly improved. Conclusion: Social participation and quality-of-life for persons instutionalized several years after cerebral anoxia were improved by psychotherapeutic and therapeutic activities. [ABSTRACT FROM AUTHOR]

Primary objective: To determine whether propofol has a neuroprotective effect on hypoxic brain injury. Research design: A hippocampal slice, in artificial cerebrospinal fluid (ASCF) with glucose and oxygen deprivation (OGD), was used as an in vitro model for brain hypoxia. Methods and procedures: The orthodromic population spike (OPS) and hypoxic injury potentia1 (HIP) were recorded in the CA1 region when Schaffer collateral was stimulated in the CA3 region of the hippocampal slices during hypoxia. The concentrations of amino acid neurotransmitters in perfusion solution of hippocampal slices were directly measured using high performance liquid chromatography (HPLC). Morphological changes of neurons, astrocytes and mitochondria in CA1 region were observed using histology and electron microscopy. Neuronal apoptosis was evaluated with TUNEL assay. Main outcome and results: Propofol treatment delayed the elimination of OPS and improved the recovery of OPS; decreased frequency of HIP, postponed the onset of HIP and increased the duration of HIP. Propofol treatment also decreased the release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but elevated the release of γ-aminobutyric acid (GABA). Morphological studies showed that propofol treatment attenuated oedema of pyramid neurons in the CA1 region and reduced apoptosis. Conclusions: Propofol has a neuro-protective effect on hippocampal neuron injury induced by hypoxia. [ABSTRACT FROM AUTHOR]

Background: Recent reports suggest that intensive, progressive training on working memory tasks can lead to generalized cognitive gains. Case study: A patient, following hypoxic brain damage, showed significant difficulties in working memory and time-perception. This study examined the impact and specificity of any benefits resulting from automated working memory training (AWMT) in comparison with the effects of an equivalent programme that emphasized automated novel problem-solving (APST) which served as an active control. Following initial assessment, the patient trained for 4 weeks (20 days), 20-30 minutes a day on the APST tasks before repeating key outcome measures. He then trained for an identical period on AWMT. Results: There were no cognitive gains apparent following APST. Furthermore, there were no disproportionate gains on digit span following AWMT. AWMT was, however, associated with improvement in time-perception that had previously been resistant to rehabilitation. In line with previous reports, AWMT was also followed by gains on a measure of planning. Conclusion: The results provide encouraging evidence that AWMT may have generalized benefits in the context of impaired WM capacity following brain injury. [ABSTRACT FROM AUTHOR]

The article discusses conflicts and tensions between health care professionals, patients and their families in ethics consultations. Topics discussed include legal regime governing surrogate decision making as highly complex, pregnancy exclusions impacting health care providers in the exercise of their autonomy and professional judgment and ethicist providing guidance based on patient rights, principles and the family's narrative.

Mild hypoxia, typically equivalent to a pressurized aircraft cabin altitude of 2,438 m (8,000 ft), does not generally affect well-learned cognitive, vigilance, and perceptual-motor performance. Learning and novel and complex cognitive tasks involving multiple demands, however, might be impaired. This study evaluated whether complex cognition—as assessed by complex reasoning, multiple memory, and risk judgment—was impaired during mild hypoxia. Using a normobaric single-blind crossover design, 25 healthy nonsmoking male participants breathed normoxic (FiO2= 0.206) or hypoxic air (FiO2= 0.143) equivalent to 2,438 m for 2 hr and performed the following tasks at baseline, 30 min, and 90 min: (a) a complex logical reasoning task that assessed accuracy, response time, and a reasoning quality index for easy (nonconflict valid), difficult (nonconflict invalid), fairly difficult (conflict valid), and very difficult (conflict invalid) syllogisms; (b) a multiple memory test that assessed sentence judgment error, working memory span, and prospective memory; and (c) a simple vigilance psychomotor task that assessed the frequency and mean time that a disc was outside a target area and braking reaction time. They also completed a self-perceived risk judgement questionnaire near the end of each exposure. After 90 min, the mean change in working memory span for mild hypoxia (M= 0.9,SD= 4.6) was significantly less than for normoxia (M= 4.4,SD= 7.2). The reasoning quality index for conflict invalid syllogisms for mild hypoxia (M= 0.22,SD= 0.29) was marginally significantly less than for normoxia (M= 0.39,SD= 0.35). The chances of these findings occurring by chance cannot be discounted, but are small. Although this study suggests that mild hypoxia might impair working memory and complex logical reasoning involving difficult conflicts, further studies using more discerning tests of cognition are warranted. [ABSTRACT FROM AUTHOR]

Tibetan nomads have lived since ancient times in the unique and harsh environment of the Qinghai-Tibetan Plateau with average altitudes over 4000 m. These people have been able to live and multiply healthily over numerous generations under the extreme stress of high-altitude environment, including cold, hypoxia, and strong ultraviolet radiation, and with a simple diet devoid of vegetables and fruits for most of the year. Their survival depends heavily on yak milk, and its products comprise the main portion of their daily diet. In this review, yak milk and its derived products are examined in detail and compared with milk from other ruminant species. Yak milk products seem to be particularly rich in functional and bioactive components, which may play a role in maintaining the health status of Tibetan nomads. This includes particular profiles of amino acids and fatty acids, and high levels of antioxidant vitamins, specific enzymes, and bacteria with probiotic activity (yoghurt is the main food). Based on that, it is proposed that the Tibetan nomads have developed a nutritional mechanism adapted to cope with the specific challenges posed by the environment of the world's highest plateau. Systematic studies are required to demonstrate this in a more mechanistic way. [ABSTRACT FROM AUTHOR]

Objective: This study describes a case of lesions of the upper motor neuronal pathway with locked-in features after lightning strike and cardiac arrest. Design: A case-review analysis. Methods: In a 29-year-old male who was hit by a lightning strike during farming activities, cardiopulmonary resuscitation was provided first by co-workers and continued with success by the medical rescue service. After conducting advanced life support under monitoring and therapeutic hypothermia, quadriplegia with facial diplegia was recognized. A review was undertaken detailing the clinical course. Results: MR imaging presented signs consistent with hypoxia-induced damage and diffusion-weighted MR images revealed pronounced damages along the upper motor neuronal pathway. A reactive electroencephalogram pattern, sustained eye movement and the patient communicating via eye-blinking were interpreted as locked-in features. Two weeks after admission the patient was transferred to a neurological rehabilitation centre for further professional care. Conclusion: Direct damage of the upper motor neuron pathway due to the current of the lightning should be considered, albeit the relative contribution of hypoxia-induced damage cannot be separated. [ABSTRACT FROM AUTHOR]

The induction of hypoxia-inducible factors (HIFs) is essential for the adaptation of tumor cells to a low-oxygen environment. We found that the expression of the apoptosis inhibitor ARC (apoptosis repressor with a CARD domain) was induced by hypoxia in a variety of cancer cell types, and its induction is primarily HIF1 dependent. Chromatin immunoprecipitation (ChIP) and reporter assays also indicate that the ARC gene is regulated by direct binding of HIF1 to a hypoxia response element (HRE) located at bp -190 upstream of the transcription start site. HIFs play an essential role in the pathogenesis of renal cell carcinoma (RCC) under normoxic conditions, through the loss of the Von Hippel-Lindau gene (VHL). Accordingly, our results show that ARC is not expressed in normal renal tissue but is highly expressed in 65% of RCC tumors, which also express high levels of carbonic anhydrase IX (CAIX), a HIF1 -dependent protein. Compared to controls, ARC-deficient RCCs exhibited decreased colony formation and increased apoptosis in vitro. In addition, loss of ARC resulted in a dramatic reduction of RCC tumor growth in SCID mice in vivo. Thus, HIF-mediated increased expression of ARC in RCC can explain how loss of VHL can promote survival early in tumor formation. [ABSTRACT FROM AUTHOR]

Objectives: Given that reliable markers for early ischemic brain damage are lacking, we set out to test whether pimonidazole can be used as a reliable tool in the quantification of hypoxic insults, at early time points following experimental stroke. Methods: We have used semi-quantitative Western blotting detection of pimonidazole adducts in a rat model of reversible middle cerebral artery occlusion (MCAO), treated with remote post-conditioning. Results: First, we demonstrated that a linear relationship exist between pimonidazole binding in the ischemic hemisphere and duration of ischemia, in animals subjected to 5, 15, 30, or 60 minutes of occlusion followed by 120 minutes of reflow. Then we showed a significant reduction in pimonidazole binding in the infarcted hemisphere, when rats with 60 minutes of MCAO, immediately after establishment of cerebral reflow, had 3×15 minutes intermittent hind limb ischemia followed by 24-hour survival. We analysed the middle cerebral arteries from animals with 60 minutes of MCAO and early remote postconditioning, followed by 30 minutes, 24, or 48 hours of reflow. At 24 hours of reflow increases in phosphorylated protein kinase C-alpha with concomitantly increased levels of p38 phosphorylation were observed. Conclusions: Our investigation demonstrates that pimonidazole can be used for quantifying ischemic impact in stroke, even after very short survival times. It furthermore shows that early remote postconditioning reduces ischemic damage, probably through hyperpolarization and reduced reflow vasospasm in the conduit middle cerebral arteries. [ABSTRACT FROM AUTHOR]

Primary objective: To compare the long-term outcome of patients with severe traumatic brain injury and patients with hypoxic brain injury with dysautonomia and hypertonia treated with intrathecal baclofen therapy. Methods and procedures: Fifty-three patients with severe traumatic ( n = 43/53) or hypoxic ( n = 10/53) brain injuries treated by intrathecal baclofen therapy were included to be evaluated with the Coma Recovery Scale-Revised, the Barthel Index, the Glasgow Outcome Scale, the Ashworth scale, the scores of hypertonic attacks, of sweating episode and of voluntary motor responses. A retrospective analysis highlighted patients' characteristics at admission and before surgery and their complications. Main outcomes and results: After a mean follow-up time of 9.6 years, 13/53 (24.5%) patients had died. Alive patients with traumatic brain injury had a higher level of consciousness recovery ( p < 0.02) and more abilities in activities of daily living ( p < 0.008) in the long-term. Their dysautonomia and limb hypertonia also significantly improved, contrary to patients with hypoxic brain injury who needed higher doses of baclofen ( p < 0.03). Conclusions: At long-term follow-up, patients with hypoxic brain injury had a poorer functional outcome than patients with traumatic brain injury with persistent symptoms of dysautonomia associated with uncontrolled hypertonia, despite the use of intrathecal baclofen. [ABSTRACT FROM AUTHOR]

Ischemia/hypoxia induces oxidative stress which is associated with neurodegenerative diseases. The present study investigated protective mechanism of carnosic acid (CA) on ischemia/reperfusion and hypoxia-induced neuronal cell injury. The results showed that CA reduced 52% of the infarct volume from brains under ischemia/reperfusion in vivo and protected the PC12 cells from hypoxic injury in vitro. CA (1.0 µM) enhanced cell viability, prevented lactic dehydrogenase (LDH) release, scavenged reactive oxygen species (ROS), increased superoxide dismutase activity, and attenuated Ca2+ release, lipid peroxidation, and prostaglandin E2 production in hypoxic PC12 cells. In addition, CA also reduced nitric oxide (NO) and interleukine (IL)-1 and IL-6 production from activated BV-2 microglia. Furthermore, its effect on hypoxia-induced mitogen-activated protein kinases (MAPKs) signaling pathway and caspase-3 was examined. Extracellular signal-regulated protein kinases, c-jun NH2-terminal kinase, and p38 MAPK were activated during hypoxia. CA inhibited MAPKs, caspase-3, and COX-2 activation and correlated well with the diminished LDH release and apoptosis (TUNEL) in PC12 cells under hypoxia. Taken together, CA protected neuronal cells under ischemia/hypoxia through scavenging or reducing of ROS and NO, inhibiting COX-2 and MAPK pathways by anti-inflammatory and anti-oxidative properties. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to assess myocardial damage in infants due to perinatal hypoxia. Methods: The findings of 29 infants with perinatal hypoxia and 20 healthy infants were compared. Blood gas analysis, serum lactate, cardiac troponin I (cTnI), troponin T (cTnT), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were evaluated. Echocardiography together with tissue Doppler imaging was performed. Results: cTnT, CK-MB and BNP were higher in patients at the first day. There were positive correlations between the left ventricular (LV) myocardial performance index (MPI) and cTnT at first day and also at first month. LV ejection fraction and fractional shortening were lower at first day and at first month in patients. Myocardial systolic (Sm) and diastolic (Em and Am) velocities at all segments were lower at first day, and interventricular septum Sm, LV Sm, LV Em, right ventricular Em and LV Am were still lower at first month in patients. Isovolumic relaxation time at all segments together with LV MPI was higher at first day, ejection time values were lower and MPI values were higher at all segments at first month in patients. Conclusions: These findings demonstrated that the signs of myocardial damage due to perinatal hypoxia still present at first month. [ABSTRACT FROM AUTHOR]

Purpose: To identify elements that could facilitate the diagnosis of cerebral visual impairment (CVI) in children with good visual acuity in the general ophthalmic clinic. Methods: We retrospectively investigated the clinical characteristics of 30 children with good visual acuity and CVI and compared them with those of 23 children who were referred with a suspicion of CVI, but proved to have a different diagnosis. Clinical characteristics included medical history, MRI findings, visual acuity, crowding ratio (CR), visual field assessment, and the results of ophthalmologic and orthoptic examination. We also evaluated the additional value of a short CVI questionnaire. Results: Eighty-three percent of the children with an abnormal medical history (mainly prematurity and perinatal hypoxia) had CVI, in contrast with none of the children with a normal medical history. Cerebral palsy, visual field defects, and partial optic atrophy only occurred in the CVI group. 41% of the children with CVI had a CR ≥2.0, which may be related to dorsal stream dysfunction. All children with CVI, but also 91% of the children without CVI gave ≥3 affirmative answers on the CVI questionnaire. Conclusion: An abnormal pre- or perinatal medical history is the most important risk factor for CVI in children, and therefore in deciding which children should be referred for further multidisciplinary assessment. Additional symptoms of cerebral damage, i.e., cerebral palsy, visual field defects, partial optic atrophy, and a CR ≥2 may support the diagnosis. CVI questionnaires should not be used for screening purposes as they yield too many false positives. [ABSTRACT FROM AUTHOR]

Autophagy is an endogenous tightly regulated process responsible for the degradation of damaged and dysfunctional cellular organelles and protein aggregates. Emerging data indicate a strong and complex interaction among autophagy, apoptosis and necrosis. We studied these interactions in a neonatal model of hypoxia-ischemia (HI). Autophagy was assessed by evaluating the expression of the two autophagy proteins beclin 1 and LC3, and by ' in vivo' autophagic vesicles formation and clearance using monodansylcadaverine (MDC). Both autophagy and apoptosis pathways were increased in the same neurons at short times after HI. Neuroprotective drugs also increased autophagy. Interestingly, pharmacological inhibition of autophagy switched cell death phenotypes from apoptosis to necrosis. Rapamycin, that enhances autophagy by inhibition of mTOR and previously shown to be neuroprotective in our animal model of HI when administered before the ischemic insult, was used to study the potential interaction between autophagy and survival pathways. Rapamycin, besides inducing autophagy, also increased Akt and CREB (cAMP response element-binding protein) phosphorylation in the same cells. The pharmacological inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt axis reduced the neuroprotective effect of rapamycin without affecting autophagy. Conversely, pharmacological inhibition of autophagy reduced the neuroprotective effect of rapamycin without affecting Akt phosphorylation. Both treatments, however, caused a rapid switch towards necrotic cell death. Thus, autophagy can be part of an integrated pro-survival signalling which includes the PI3K-Akt- mTOR axis and its activation seems be crucial for pharmacological and ischemic preconditioning. [ABSTRACT FROM AUTHOR]

Primary objective: This study was designed to evaluate the effect of hypobaric hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus CA1 pyramidal cells. Research design: The functional changes of P2X receptors were investigated through the cell HH model and the expressional alterations of P2X receptors were observed through the animal HH model. Methods and procedure: P2X receptors mediated currents were recorded from the freshly dissociated CA1 pyramidal cells of 7--day--old SD rats by whole cell patch clamp recording. The expression and distribution of P2X receptors were observed through immunohistochemistry and western blot at HH 3--day and 7--day. Main outcomes and results: In acute HH conditions, the amplitudes of ATP evoked peak currents were decreased compared to control. The immunohistochemistry and western blot results reflected there was no change in P2X receptors expression after 3 days HH injury, while P2X receptors expression was up--regulated in response to 7 days HH injury. Conclusions: These findings supported the possibility that the function of P2X receptors was sensitive to HH damage and long--term function decrease should result in the expression increase of P2X receptors. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to investigate the possible neuroprotective and ameliorating effects of leptin treatment in hypoxic-ischemic injury induced neuronal cell death. Methods. Experimental groups in the study were: sham-operated group, leptin treated hypoxia-ischemia group, and vehicle treated hypoxia-ischemia group. In hypoxia-ischemia group, left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92%% nitrogen and 8%% oxygen) was applied for 2.5 h. Leptin treatment was injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. Neuronal cell death, neuronal density, and leptin levels were evaluated in both hemispheres 72 h after the hypoxic-ischemic insult. Results. Compared with the hypoxic-ischemia group, the mean leptin levels were higher in the brains of the sham group for both hemispheres. The leptin treatment significantly diminished the number of 'apoptotic cells' in the hippocampal CA1, CA2, CA3, and gyrus dentatus regions in both hemispheres. Leptin treatment significantly preserved the number of neurons in both hemispheres, when compared with the vehicle treated group. Conclusion. We conclude that leptin treatment improves neuronal density and decreases apoptosis in the newborn rat with hypoxic-ischemic brain injury. [ABSTRACT FROM AUTHOR]

Primary objective: Recent evidence suggests that delayed hypoxic post-conditioning is neuroprotective. The aim of the present study was to test whether early post-conditioning applied immediately after hypoxia could protect cultured neurons from hypoxia/reoxygenation (H/R)-induced injuries. Methods: Primary cortical neuronal culture depleted of microglia was exposed to H/R. Post-conditioning started immediately after hypoxia and consisted of three cycles of 15-minutes of reoxygenation and 15-minutes of hypoxia. Cell viability assay was performed using Cell Counting Kit-8 (CCK-8). Apoptosis was evaluated by Hoechst 33258 staining, FITC-Annexin V/PI double staining and Western blot assay (testing the cleaved caspase-3 expression). Reactive oxygen species (ROS), intracellular Ca2++ and mitochondrial membrane potential (MMP) were examined using confocal laser-scanning microscopy. Main results: H/R significantly reduced cell viability and increased neuronal apoptosis and necrosis. Furthermore, the expression of cleaved caspase-3, ROS production and intracellular Ca2++ were increased. MMP was attenuated. Injuries induced by H/R were substantially attenuated by early hypoxic post-conditioning. Changes in cleaved caspase-3 expression, ROS production, intracellular Ca2++ level and MMP in response to H/R were significantly decreased by the post-conditioning. Conclusions: The findings demonstrated that early hypoxic post-conditioning could protect neurons against H/R-induced injuries independent of microglial cells, possibly by inhibiting ROS over-production and intracellular Ca2++ accumulation and maintaining MMP. [ABSTRACT FROM AUTHOR]

Our objective was to determine whether apathy in amyotrophic lateral sclerosis (ALS) relates to structural changes associated with the degenerative process or disease related factors such as illness duration, physical disability, or hypoxia. Using diffusion tensor imaging (DTI) with fractional anisotropy (FA), we conducted a voxel-based analysis of whole-brain changes to investigate decline in white matter integrity as it correlates with apathy in ALS. Twenty-four patients enrolled in the study were compared with 24 age- and gender-matched controls. The relationship between FA and apathy scores was tested using a general linear model accounting for age, gender and functional disability in 16 ALS patients. Results showed that, using a spatially unbiased voxel-wise approach and the statistical map-driven region of interest (ROI), a significant negative correlation existed between FA and apathy change scores in the right anterior cingulum region, whereas ALS disease severity was significantly correlated with FA alterations in bilateral motor areas. Apathy was not correlated with clinical depression, disease duration or respiratory dysfunction. In conclusion, our findings point towards a biological basis for apathy in the anterior cingulum, consistent with research on apathy in other neurological populations. [ABSTRACT FROM AUTHOR]

Combustion smoke contains gases and particulates, which act via hypoxia and cytotoxicity producing mechanisms to injure cells and tissues. While carbon monoxide (CO) is the major toxicant in smoke, its toxicity is exacerbated in the presence of other compounds. Here, we examined modulations of mitochondrial and cytosolic energy metabolism by inhalation of combustion smoke versus CO, in vivo, in the rat brain. Measurements revealed reduced activities of respiratory chain (RC) complexes, with greater inhibition by smoke than equivalent CO in ambient air. In the case of RC complex IV, inhibition by CO and smoke was similar—suggesting that complex IV inhibition is primarily by the action of CO. In contrast, inhibition of complexes I and III was greater by smoke. Increases in cytosolic lactate dehydrogenase and pyruvate kinase activities accompanied inhibition of RC complexes, likely reflecting compensatory increases in cytosolic energy production. Together, the data provide new insights into the mechanisms of smoke inhalation-induced perturbations of brain energetics, which impact neuronal function and contribute to the development of neuropathologies in survivors of exposures to CO and combustion smoke. [ABSTRACT FROM AUTHOR]

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces life-threatening pulmonary edema within hours of exposure; no antidote exists. This study examines pathophysiological changes seen following treatment with elevated inspired oxygen concentrations (Fi2), in a model of phosgene-induced acute lung injury. Anesthetized pigs were exposed to phosgene (Ct 2500 mg min m−3) and ventilated (intermittent positive pressure ventilation, tidal volume 10 ml kg−1, positive end-expiratory pressure 3 cm H2O, frequency 20 breaths min−1). The Fi2 was varied: group 1, Fi2 0.30 (228 mm Hg) throughout; group 2, Fi2 0.80 (608 mm Hg) immediately post exposure, to end; group 3, Fi2 0.30 from 30 min post exposure, increased to 0.80 at 6 h post exposure; group 4, Fi2 0.30 from 30 min post exposure, increased to 0.40 (304 mm Hg) at 6 h post exposure. Group 5, Fi2 0.30 from 30 min post exposure, increased to 0.40 at 12 h post exposure. The current results demonstrate that oxygen is beneficial, with improved survival, arterial oxygen saturation, shunt fraction, and reduced lung wet weight to body weight ratio in all treatment groups, and improved arterial oxygen partial pressure in groups 2 and 3, compared to phosgene controls (group 1) animals. The authors recommend that treatment of phosgene-induced acute lung injury with inspired oxygen is delayed until signs or symptoms of hypoxia are present or arterial blood oxygenation falls. The lowest concentration of oxygen that maintains normal arterial oxygen saturation and absence of clinical signs of hypoxia is recommended. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the protective effects of adenosine against hypoxic injury at hypothermia; both magnitude and mechanisms. Design. Receptor versus non-receptor dependent mechanisms in cardioprotection by adenosine were examined in guinea pig papillary muscles exposed to glucose free hypoxia at 24°C. Contractile force amplitude (CFA) and action potential duration (APD) during increasing concentrations of adenosine at 37°C, 30°C and 24°C normoxia were also examined. Results. CFA was significantly improved after adenosine treatment during hypothermic hypoxia compared to control (80.7±17.4% vs 40.5±10.7%, p<0.001). Adenosine receptor antagonist SPT did not antagonize (64.6±21.1%), and adenosine receptor agonists (APNEA+NECA) could not mimic the cardioprotection (53.8±9.3%). MitoKCa blocker paxilline antagonized the cardioprotection (40.0±7.7%). During normoxic conditions hypothermia-induced increase in CFA was significantly decreased by adenosine (0.12–12 mM) whereas the increase in action potential duration was potentiated. Conclusion. Adenosine (1.2 mM) had marked cardioprotective effect in hypothermic substrate free hypoxia. Possible mechanisms are non-receptor dependent and related to mitoKCa channels. The cardiodepressive effect at hypothermia may contribute to cardioplegia. [ABSTRACT FROM AUTHOR]

Primary objective: Cardiac arrest can cause neurological impairment. The aim of this study is to confirm the disability and the predominant part of executive and behavioural impairments after cardiac arrest. Research design: A retrospective study is proposed. Methods and procedures: All consecutive patients admitted to the Department of Rehabilitation for Neurological Impairments following cerebral anoxia after cardiac arrest between 1995–2007 were included. Clinical and neuropsychological assessment was proposed. Main outcomes and results: Thirty patients, 19 men, were examined. Ages ranged from 16–58 (mean = 39.5). Fourteen patients presented with severe disability and 16 patients presented with moderate disability. In the first group (severe disability) no patients were autonomous for daily life activities. They presented with dysexecutive syndrome and behavioural disorders associated with amnesia syndrome; 64% of them presented with motor disorders. In the second group, patients with moderate disability were autonomous in daily life but not for the complex activities or functioning. They had no motor impairment but suffered from executive and memory impairments. Behavioural changes were noted. Medical history or demographic data did not differ between the two groups. Conclusion: The study confirms the predominant part of executive, memory and behavioural impairments after cardiac arrest. This retrospective study cannot provide prognosis factors and further prognosis studies are needed. [ABSTRACT FROM AUTHOR]

The burst suppression (BS) pattern of the EEG was originally described as a response to large dosages of anesthetics and sedatives, It was subsequently found over/in isolated cortex due to surgical procedures or lesions underlying the cortex. Around 1960 with the introduction of modern intensive care treatment (intubation, artificial respiration) the BS pattern has become a typical EEG correlate of cerebral anoxia. These obvious consequences of this therapeutic approach with their impact on the EEG picture are more or less inexplicable. The BS pattern is also typical in two rare and severe central nervous system (CNS) disorders in infants: early infantile myoclonic encephalopathy (EIME) and Ohtahara syndrome. [ABSTRACT FROM AUTHOR]