Hyperbaric Oxygen Prevents Early Death Caused by Experimental Cerebral Malaria

Background: Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis. Methodology/Principal Findings: C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O(2), 3.0 ATA, 1-2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-alpha, IFN-gamma and IL-10 mRNA levels and percentage of gamma delta and alpha beta CD4(+) and CD8(+) T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB)dysfunction and hypothermia. Conclusions/Significance: The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.

Anticipatory and compensatory postural adjustments in sitting in children with cerebral palsy

The aim of this study was to examine postural control in children with cerebral palsy performing a bilateral shoulder flexion to grasp a ball from a sitting posture. The participants were 12 typically developing children (control) without cerebral palsy and 12 children with cerebral palsy (CP). We analyzed the effect of ball mass (1 kg and 0.18 kg), postural adjustment (anticipatory, APA, and compensatory, CPA), and groups (control and CP) on the electrical activity of shoulder and trunk muscles with surface electromyography (EMG). Greater mean iEMG was seen in CPA, with heavy ball, and for posterior trunk muscles (p < .05). The children with CP presented the highest EMG and level of co-activation (p < .05). Linear regression indicated a positive relationship between EMG and aging for the control group, whereas that relationship was negative for participants with CP. We suggest that the main postural control strategy in children is based on corrections after the beginning of the movement. The linear relationship between EMG and aging suggests that postural control development is affected by central nervous disease which may lead to an increase in muscle co-activation. (C) 2011 Elsevier B.V. All rights reserved.

Characterization of the electrocardiographic pattern of individuals with cerebral palsy

Background: Dentists of Lar Sao Francisco observed during dental treatment that children with cerebral palsy (CP) had increased heart rate (HR) and lower production of saliva. Despite the high prevalence of CP found in the literature (2.08-3.6/1000 individuals), little is known about the electrocardiographic (ECG) characteristics, especially HR, of individuals with CP. Objective: This study aimed to investigate the hypothesis that individuals with CP have a higher HR and to define other ECG characteristics of this population. Methods: Ninety children with CP underwent clinical examination and 12-lead rest ECG. Electrocardiographic data on rhythm, HR, PR interval, QRS duration, P/QRS/T axis, and QT, QTc and T(peak-end) intervals (minimum, mean, maximum, and dispersion) were measured and analyzed then compared with data from a control group with 35 normal children. Fisher and Mann-Whitney U tests were used, respectively, to compare categorical and continuous data. Results: Groups cerebral palsy and control did not significantly differ in age (9 +/- 3 x 9 +/- 4 years) and male gender (65% x 49%). Children with CP had a higher HR (104.0 +/- 20.6 x 84.2 +/- 13.3 beats per minute; P < .0001), shorter PR interval (128.8 +/- 15.0 x 138.1 +/- 15.1 milliseconds; P = .0018), shorter QRS duration (77.4 +/- 8.6 x 82.0 +/- 8.7 milliseconds; P = .0180), QRS axis (46.0 degrees +/- 26.3 degrees x 59.7 degrees +/- 24.8 degrees; P = .0024) and T-wave axis (34.3 degrees +/- 28.9 degrees x 42.9 degrees +/- 17.1 degrees; P = .034) more horizontally positioned, and greater mean QTc (418.1 +/- 18.4 x 408.5 +/- 19.4 milliseconds; P = .0110). All the electrocardiogram variables were within the reference range for the age group including those with significant differences. Conclusion: Children with CP showed increased HR and other abnormal ECG findings in the setting of this investigation. Further studies are needed to explain our findings and to correlate the increased HR with situations such as dehydration, stress, and autonomic nervous disorders. (C) 2011 Elsevier Inc. All rights reserved.

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pairfed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs, that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity. (C) 1999 Elsevier Science B.V. All rights reserved.

Hypoxia stimulates cerebral blood flow in the estuarine crocodile (Crocodylus porosus)

The effect of N-2 respiration on cerebral blood flow (CBF) velocity on the dorsal surface of cerebellum was examined in the estuarine crocodile, Crocodylus porosus, using epi-illumination microscopy. Twelve minutes of N-2 respiration resulted in a 126% increase in CBF velocity. N-2 respiration had no effect on blood pressure, indicating an underlying cerebral vasodilation. In addition, heart rate increased significantly. Systemic injections of aminophylline and the NO synthase (NOS) inhibitor nitro-L-arginine (L-NA) did not affect the hypoxia induced increase in CBF. We conclude that C. porosus responds to hypoxia with adenosine and nitric oxide (NO) independent cerebral vasodilation, and that this is likely to be a mechanism protecting the brain from energy deficiency during prolonged dives. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

Regarding "Edema and leg volume: Methods of assessment" (Letters to the Editor)

I noted with interest the article by Drs Perrin and Guex, entitled &dquo;Edema and leg volume: Methods of assessment,&dquo; published in Angiology 51:9-12, 2000. This was a timely and comprehensive review of the various methods in clinical use for the assessment of peripheral edema, notably in the leg. I would like to take this opportunity to alert readers to a further technique useful for this purpose, namely, bioelectrical impedance analysis. An early reportl described its use for the measurement of edema in the leg, but other than its successful use for the assessment of edema in the arm following masteCtoMy,2,1 the potential of the method remains to be fully realized. This is unfortunate since the method directly and quantifiably measures edema.

Dental caries in cerebral palsied individuals and their caregivers` quality of life

To study the correlation between caries experience in individuals with cerebral palsy (CP) and the quality of life of their primary caregivers. Sixty-five non-institutionalized individuals, presenting CP, aged 2-21 years old, were evaluated for caries experience. Their respective caregivers aged 20-74 years old answered the Short Form 36 (SF-36) health survey and Independence Measure for Children. Fifty-eight non-disabled individuals (ND group), aged 2-21 years old, and their respective caregivers, aged 25-56 years old, were submitted to the same evaluation process as the CP group. Primary caregivers of CP individuals exhibited significantly lower scores than the ND group in all subscales of the SF-36 health survey questionnaire: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role and mental health. The CP group presented significantly higher values for the Decayed, Missed and Filled (DMF-T) index than the ND group and a significant negative correlation was obtained between the SF-36 and DMF-T index. The results suggest that caregivers of CP individuals exhibited worse quality of life than those of the non-disabled. A negative correlation exists between caries experience of CP individuals and their caregivers` quality of life.

Combined Laser and Intravitreal Triamcinolone for Proliferative Diabetic Retinopathy and Macular Edema: One-year Results of a Randomized Clinical Trial

PURPOSE: To evaluate laser combined with intravitreal triamcinolone acetonide (IVTA) for the management of patients with proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME). DESIGN: Randomized clinical trial. METHODS: SETTINGS: Single center. STUDY POPULATION: Twenty-two patients with bilateral treatment,naive moderate PDR and CSME. INTERVENTION: Laser (panretinal and macular) photocoagulation was performed in each eye, followed by IVTA in one randomly assigned eye. Best,corrected visual acuity (BCVA), fundus photography, and optical coherence tomography were performed at baseline and at months 1, 3, 6, 9, and 12. MAIN OUTCOME MEASURES:. Changes in BCVA, central macular thickness (CMT), and total macular volume (TMV). RESULTS: The mean logarithm of the minimal angle of resolution (logMAR) BCVA improved significantly, and mean CMT and TMV were significantly reduced in the IVTA group compared with the laser,only group (controls) at all study follow-up visits (P < .001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50(-2)) for the IVTA group and 0.38 (20/50(+1)) for the controls at baseline, and 0.12 (20/25(-1)) for the IVTA group and 0.32 (20/40(-1)) for the controls at 12 months (P < .001.). The mean CMT and TMV were, respectively, 360 mu m and 8.59 mm(3) for the IVTA group and 331 mu m and 8.44 mm(3) for the controls at baseline, and 236 mu m and 7.32 mm(3) for the IVTA group and 266 mu m and 7.78 mm(3) for the controls at 12 months (P < .001). CONCLUSIONS: The combination of laser photocoagulation with IVTA was associated with improved BCVA and decreased CMT and TMV when compared with laser photocoagulation alone for the treatment of moderate PDR with CSME. (Am J Ophthalmol 2009;147:291-297. (C) 2009 by Elsevier Inc. All rights reserved.)

Microsurgical Anatomy of the Posterior Cerebral Artery in Three-Dimensional Images

OBJECTIVE: To describe the microsurgical anatomy, branches, and anatomic relationships of the posterior cerebral artery (PCA) represented in three-dimensional images. METHODS: Seventy hemispheres of 35 brain specimens were studied. They were previously injected with red silicone and fixed in 10% formalin for at least 40 days. Four of the studied specimens were frozen at -10 degrees to -15 degrees C for 14 days, and additional dissection was done with the Klingler`s fiber dissection technique at x6 to x40 magnification. Each segment of the artery was measured and photographed to obtain three-dimensional stereoscopic images. RESULTS: The PCA origin was in the interpeduncular cistern at the pontomesencephalic junction level in 23 specimens (65.7%). The PCA was divided into four segments: P1 extends from the PCA origin to its junction with the posterior communicating artery with an average length of 7.7 mm; P2 was divided into an anterior and posterior segment. The P2A segment begins at the posterior communicating artery and ends at the most lateral aspect of the cerebral peduncle, with an average length of 23.6 mm, and the P2P segment extends from the most lateral aspect of the cerebral peduncle to the posterior edge of the lateral surface of the midbrain, with an average length of 16.4 mm; P3 extends from the posterior edge of the lateral surface of the midbrain and ends at the origin of the parieto-occipital sulcus along the calcarine fissure, with an average length of 19.8 mm; and the P4 segment corresponds to the parts of the PCA that run along or inside both the parieto-occipital sulcus and the distal part of the calcarine fissure. CONCLUSIONS: To standardize the neurosurgical practice and knowledge, surgical anatomic classifications should be used uniformly and further modified according to the neurosurgical experience gathered. The PCA classification proposed intends to correlate its anatomic segments with their required microneurosurgical approaches.

A stepwise approach to stroke surveillance in Brazil: the EMMA (Estudo de Mortalidade e Morbidade do Acidente Vascular Cerebral) study

Background Stroke mortality rates in Brazil are the highest in the Americas. Deaths from cerebrovascular disease surpass coronary heart disease. Aim To verify stroke mortality rates and morbidity in an area of Sao Paulo, Brazil, using the World Health Organization Stepwise Approach to Stroke Surveillance. Methods We used the World Health Organization Stepwise Approach to Stroke Surveillance structure of stroke surveillance. The hospital-based data comprised fatal and nonfatal stroke (Step 1). We gathered stroke-related mortality data in the community using World Health Organization questionnaires (Step 2). The questionnaire determining stroke prevalence was activated door to door in a family-health-programme neighbourhood (Step 3). Results A total of 682 patients 18 years and above, including 472 incident cases, presented with cerebrovascular disease and were enrolled in Step 1 during April-May 2009. Cerebral infarction (84 center dot 3%) and first-ever stroke (85 center dot 2%) were the most frequent. In Step 2, 256 deaths from stroke were identified during 2006-2007. Forty-four per cent of deaths were classified as unspecified stroke, 1/3 as ischaemic stroke, and 1/4 due to haemorrhagic subtype. In Step 3, 577 subjects over 35 years old were evaluated at home, and 244 cases of stroke survival were diagnosed via a questionnaire, validated by a board-certified neurologist. The population demographic characteristics were similar in the three steps, except in terms of age and gender. Conclusion By including data from all settings, World Health Organization stroke surveillance can provide data to help plan future resources that meet the needs of the public-health system.

Conditioning training and retrieval increase phospholipase A(2) activity in the cerebral cortex of rats

In rats, phospholipase A(2) (PLA(2)) activity was found to be increased in the hippocampus immediately after training and retrieval of a contextual fear conditioning paradigm (step-down inhibitory avoidance [IA] task). In the present study we investigated whether PLA(2) is also activated in the cerebral cortex of rats in association with contextual fear learning and retrieval. We observed that IA training induces a rapid (immediately after training) and long-lasting (3 h after training) activation of PLA(2) in both frontal and parietal cortices. However, immediately after retrieval (measured 24 h after training), PLA(2) activity was increased just in the parietal cortex. These findings suggest that PLA(2) activity is differentially required in the frontal and parietal cortices for the mechanisms of contextual learning and retrieval. Because reduced brain PLA(2) activity has been reported in Alzheimer disease, our results suggest that stimulation of PLA(2) activity may offer new treatment strategies for this disease.